CA2992789A1 - Combination therapy using liposomal irinotecan and a parp inhibitor for cancer treatment - Google Patents
Combination therapy using liposomal irinotecan and a parp inhibitor for cancer treatment Download PDFInfo
- Publication number
- CA2992789A1 CA2992789A1 CA2992789A CA2992789A CA2992789A1 CA 2992789 A1 CA2992789 A1 CA 2992789A1 CA 2992789 A CA2992789 A CA 2992789A CA 2992789 A CA2992789 A CA 2992789A CA 2992789 A1 CA2992789 A1 CA 2992789A1
- Authority
- CA
- Canada
- Prior art keywords
- irinotecan
- days
- inhibitor
- parp inhibitor
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 title claims abstract description 322
- 229960004768 irinotecan Drugs 0.000 title claims abstract description 286
- 239000012661 PARP inhibitor Substances 0.000 title claims abstract description 243
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 title claims abstract description 243
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 217
- 238000011282 treatment Methods 0.000 title claims abstract description 104
- 201000011510 cancer Diseases 0.000 title claims abstract description 67
- 238000002648 combination therapy Methods 0.000 title abstract description 8
- JNAHVYVRKWKWKQ-CYBMUJFWSA-N veliparib Chemical compound N=1C2=CC=CC(C(N)=O)=C2NC=1[C@@]1(C)CCCN1 JNAHVYVRKWKWKQ-CYBMUJFWSA-N 0.000 claims abstract description 180
- 229950011257 veliparib Drugs 0.000 claims abstract description 179
- 239000003112 inhibitor Substances 0.000 claims abstract description 94
- 206010008342 Cervix carcinoma Diseases 0.000 claims abstract description 47
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims abstract description 47
- 201000010881 cervical cancer Diseases 0.000 claims abstract description 47
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 39
- 229960000572 olaparib Drugs 0.000 claims description 87
- 229940102709 ferumoxytol Drugs 0.000 claims description 78
- UCNNJGDEJXIUCC-UHFFFAOYSA-L hydroxy(oxo)iron;iron Chemical compound [Fe].O[Fe]=O.O[Fe]=O UCNNJGDEJXIUCC-UHFFFAOYSA-L 0.000 claims description 76
- HMABYWSNWIZPAG-UHFFFAOYSA-N rucaparib Chemical compound C1=CC(CNC)=CC=C1C(N1)=C2CCNC(=O)C3=C2C1=CC(F)=C3 HMABYWSNWIZPAG-UHFFFAOYSA-N 0.000 claims description 39
- 229950004707 rucaparib Drugs 0.000 claims description 39
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims description 36
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 claims description 33
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 claims description 33
- 230000000118 anti-neoplastic effect Effects 0.000 claims description 29
- PCHKPVIQAHNQLW-CQSZACIVSA-N niraparib Chemical group N1=C2C(C(=O)N)=CC=CC2=CN1C(C=C1)=CC=C1[C@@H]1CCCNC1 PCHKPVIQAHNQLW-CQSZACIVSA-N 0.000 claims description 27
- 229950011068 niraparib Drugs 0.000 claims description 26
- HWGQMRYQVZSGDQ-HZPDHXFCSA-N chembl3137320 Chemical compound CN1N=CN=C1[C@H]([C@H](N1)C=2C=CC(F)=CC=2)C2=NNC(=O)C3=C2C1=CC(F)=C3 HWGQMRYQVZSGDQ-HZPDHXFCSA-N 0.000 claims description 24
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 23
- 208000003721 Triple Negative Breast Neoplasms Diseases 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 229950004550 talazoparib Drugs 0.000 claims description 23
- 208000022679 triple-negative breast carcinoma Diseases 0.000 claims description 23
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 21
- 201000002528 pancreatic cancer Diseases 0.000 claims description 21
- 206010033128 Ovarian cancer Diseases 0.000 claims description 20
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 19
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 19
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 17
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 17
- 206010009944 Colon cancer Diseases 0.000 claims description 15
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 15
- 239000012458 free base Substances 0.000 claims description 15
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 9
- 206010017758 gastric cancer Diseases 0.000 claims description 9
- 201000011549 stomach cancer Diseases 0.000 claims description 9
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 8
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 8
- 230000008030 elimination Effects 0.000 claims description 6
- 238000003379 elimination reaction Methods 0.000 claims description 6
- 239000012216 imaging agent Substances 0.000 claims description 6
- 230000036470 plasma concentration Effects 0.000 claims description 6
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims description 4
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims description 4
- 201000002120 neuroendocrine carcinoma Diseases 0.000 claims description 4
- FAQDUNYVKQKNLD-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC2=C3[CH]C=CC=C3C(=O)N=N2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FAQDUNYVKQKNLD-UHFFFAOYSA-N 0.000 claims 2
- 238000000034 method Methods 0.000 abstract description 63
- 239000003534 dna topoisomerase inhibitor Substances 0.000 abstract description 41
- 229940044693 topoisomerase inhibitor Drugs 0.000 abstract description 41
- 231100000419 toxicity Toxicity 0.000 abstract description 31
- 230000001988 toxicity Effects 0.000 abstract description 31
- 239000000203 mixture Substances 0.000 abstract description 25
- 238000009472 formulation Methods 0.000 abstract description 24
- 230000002035 prolonged effect Effects 0.000 abstract description 15
- 230000008901 benefit Effects 0.000 abstract description 10
- 238000009825 accumulation Methods 0.000 abstract description 9
- 230000002093 peripheral effect Effects 0.000 abstract description 9
- 230000001225 therapeutic effect Effects 0.000 abstract description 7
- 241000283715 Damaliscus lunatus Species 0.000 abstract 1
- 101100481875 Drosophila melanogaster topi gene Proteins 0.000 abstract 1
- FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 description 174
- FDLYAMZZIXQODN-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC=2C3=CC=CC=C3C(=O)NN=2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FDLYAMZZIXQODN-UHFFFAOYSA-N 0.000 description 87
- 210000004027 cell Anatomy 0.000 description 86
- 210000002381 plasma Anatomy 0.000 description 41
- 239000003814 drug Substances 0.000 description 35
- 230000000694 effects Effects 0.000 description 35
- 238000002595 magnetic resonance imaging Methods 0.000 description 32
- 229940079593 drug Drugs 0.000 description 30
- 210000001519 tissue Anatomy 0.000 description 30
- 238000000338 in vitro Methods 0.000 description 28
- 241000699670 Mus sp. Species 0.000 description 26
- 101710183280 Topoisomerase Proteins 0.000 description 26
- 230000037396 body weight Effects 0.000 description 23
- 239000003795 chemical substances by application Substances 0.000 description 22
- 238000005259 measurement Methods 0.000 description 20
- 230000004044 response Effects 0.000 description 17
- 239000002207 metabolite Substances 0.000 description 16
- 208000004235 neutropenia Diseases 0.000 description 16
- 238000009097 single-agent therapy Methods 0.000 description 16
- 230000003442 weekly effect Effects 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 15
- 238000001802 infusion Methods 0.000 description 15
- 230000005764 inhibitory process Effects 0.000 description 15
- 230000003902 lesion Effects 0.000 description 15
- 239000002502 liposome Substances 0.000 description 15
- 230000037361 pathway Effects 0.000 description 15
- 208000026310 Breast neoplasm Diseases 0.000 description 14
- 230000003833 cell viability Effects 0.000 description 14
- 238000001727 in vivo Methods 0.000 description 14
- 206010006187 Breast cancer Diseases 0.000 description 13
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 13
- 229960002949 fluorouracil Drugs 0.000 description 13
- 238000003384 imaging method Methods 0.000 description 13
- 230000004083 survival effect Effects 0.000 description 13
- 206010020751 Hypersensitivity Diseases 0.000 description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 12
- 230000008859 change Effects 0.000 description 12
- 102220002645 rs104894309 Human genes 0.000 description 12
- 238000001574 biopsy Methods 0.000 description 11
- 230000003247 decreasing effect Effects 0.000 description 11
- 238000000151 deposition Methods 0.000 description 11
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 11
- 206010012735 Diarrhoea Diseases 0.000 description 10
- 241001529936 Murinae Species 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 229950010538 irinotecan hydrochloride trihydrate Drugs 0.000 description 10
- 229960000303 topotecan Drugs 0.000 description 10
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 10
- 230000005778 DNA damage Effects 0.000 description 9
- 231100000277 DNA damage Toxicity 0.000 description 9
- -1 MM-398) Chemical compound 0.000 description 9
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 description 9
- 210000000481 breast Anatomy 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 229940090044 injection Drugs 0.000 description 9
- KLEAIHJJLUAXIQ-JDRGBKBRSA-N irinotecan hydrochloride hydrate Chemical compound O.O.O.Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 KLEAIHJJLUAXIQ-JDRGBKBRSA-N 0.000 description 9
- 230000035772 mutation Effects 0.000 description 9
- 229940048191 onivyde Drugs 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 108010051152 Carboxylesterase Proteins 0.000 description 8
- 102000013392 Carboxylesterase Human genes 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 229940127093 camptothecin Drugs 0.000 description 8
- 230000007812 deficiency Effects 0.000 description 8
- 230000003111 delayed effect Effects 0.000 description 8
- 230000008021 deposition Effects 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- 238000010172 mouse model Methods 0.000 description 8
- 230000003389 potentiating effect Effects 0.000 description 8
- 230000002195 synergetic effect Effects 0.000 description 8
- 102000036365 BRCA1 Human genes 0.000 description 7
- 108700020463 BRCA1 Proteins 0.000 description 7
- 101150072950 BRCA1 gene Proteins 0.000 description 7
- 102000052609 BRCA2 Human genes 0.000 description 7
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 7
- 230000033616 DNA repair Effects 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 102100034533 Histone H2AX Human genes 0.000 description 7
- 101001067891 Homo sapiens Histone H2AX Proteins 0.000 description 7
- 206010028813 Nausea Diseases 0.000 description 7
- 206010047700 Vomiting Diseases 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000002246 antineoplastic agent Substances 0.000 description 7
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 7
- JYEFSHLLTQIXIO-SMNQTINBSA-N folfiri regimen Chemical compound FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 JYEFSHLLTQIXIO-SMNQTINBSA-N 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 230000008693 nausea Effects 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 230000002611 ovarian Effects 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 230000008439 repair process Effects 0.000 description 7
- 238000013414 tumor xenograft model Methods 0.000 description 7
- 230000008673 vomiting Effects 0.000 description 7
- 108700020462 BRCA2 Proteins 0.000 description 6
- 101150008921 Brca2 gene Proteins 0.000 description 6
- 102000015087 Poly (ADP-Ribose) Polymerase-1 Human genes 0.000 description 6
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 229940048115 irinotecan liposomal Drugs 0.000 description 6
- 229910052742 iron Inorganic materials 0.000 description 6
- 230000028617 response to DNA damage stimulus Effects 0.000 description 6
- 230000002459 sustained effect Effects 0.000 description 6
- 229920000858 Cyclodextrin Polymers 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 102100029152 UDP-glucuronosyltransferase 1A1 Human genes 0.000 description 5
- 101710205316 UDP-glucuronosyltransferase 1A1 Proteins 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 208000026935 allergic disease Diseases 0.000 description 5
- 208000007502 anemia Diseases 0.000 description 5
- 230000030833 cell death Effects 0.000 description 5
- 208000020832 chronic kidney disease Diseases 0.000 description 5
- 210000001072 colon Anatomy 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 229940086604 feraheme Drugs 0.000 description 5
- 230000009610 hypersensitivity Effects 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 230000035699 permeability Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 210000004881 tumor cell Anatomy 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 210000005166 vasculature Anatomy 0.000 description 5
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 4
- 208000004998 Abdominal Pain Diseases 0.000 description 4
- 206010061818 Disease progression Diseases 0.000 description 4
- 206010065973 Iron Overload Diseases 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 230000005750 disease progression Effects 0.000 description 4
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 4
- 235000008191 folinic acid Nutrition 0.000 description 4
- 239000011672 folinic acid Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 229960001691 leucovorin Drugs 0.000 description 4
- 201000002364 leukopenia Diseases 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 206010043554 thrombocytopenia Diseases 0.000 description 4
- 238000011269 treatment regimen Methods 0.000 description 4
- 210000004981 tumor-associated macrophage Anatomy 0.000 description 4
- LTZZZXXIKHHTMO-UHFFFAOYSA-N 4-[[4-fluoro-3-[4-(4-fluorobenzoyl)piperazine-1-carbonyl]phenyl]methyl]-2H-phthalazin-1-one Chemical compound FC1=C(C=C(CC2=NNC(C3=CC=CC=C23)=O)C=C1)C(=O)N1CCN(CC1)C(C1=CC=C(C=C1)F)=O LTZZZXXIKHHTMO-UHFFFAOYSA-N 0.000 description 3
- MDOJTZQKHMAPBK-UHFFFAOYSA-N 4-iodo-3-nitrobenzamide Chemical compound NC(=O)C1=CC=C(I)C([N+]([O-])=O)=C1 MDOJTZQKHMAPBK-UHFFFAOYSA-N 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- 208000009011 Cytochrome P-450 CYP3A Inhibitors Diseases 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 108010042407 Endonucleases Proteins 0.000 description 3
- 102000004533 Endonucleases Human genes 0.000 description 3
- 208000002633 Febrile Neutropenia Diseases 0.000 description 3
- 206010022971 Iron Deficiencies Diseases 0.000 description 3
- 208000015710 Iron-Deficiency Anemia Diseases 0.000 description 3
- 101710179684 Poly [ADP-ribose] polymerase Proteins 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 230000018199 S phase Effects 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- WEPNHBQBLCNOBB-UGDNZRGBSA-N [(2r,3r,4s,5r,6r)-2-[(2s,3s,4r,5r)-3,4-disulfooxy-2,5-bis(sulfooxymethyl)oxolan-2-yl]oxy-3,5-disulfooxy-6-(sulfooxymethyl)oxan-4-yl] hydrogen sulfate Chemical compound OS(=O)(=O)O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](COS(=O)(=O)O)O[C@@]1(COS(O)(=O)=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@@H](COS(O)(=O)=O)O1 WEPNHBQBLCNOBB-UGDNZRGBSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 208000037844 advanced solid tumor Diseases 0.000 description 3
- 206010003549 asthenia Diseases 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000022131 cell cycle Effects 0.000 description 3
- 238000012054 celltiter-glo Methods 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 201000011024 colonic benign neoplasm Diseases 0.000 description 3
- 208000029742 colonic neoplasm Diseases 0.000 description 3
- 238000002591 computed tomography Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000007717 exclusion Effects 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 239000012737 fresh medium Substances 0.000 description 3
- 231100001022 leukopenia Toxicity 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 231100000682 maximum tolerated dose Toxicity 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 206010061289 metastatic neoplasm Diseases 0.000 description 3
- 239000002105 nanoparticle Substances 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 238000002203 pretreatment Methods 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 231100000057 systemic toxicity Toxicity 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- DENYZIUJOTUUNY-MRXNPFEDSA-N (2R)-14-fluoro-2-methyl-6,9,10,19-tetrazapentacyclo[14.2.1.02,6.08,18.012,17]nonadeca-1(18),8,12(17),13,15-pentaen-11-one Chemical compound FC=1C=C2C=3C=4C(CN5[C@@](C4NC3C1)(CCC5)C)=NNC2=O DENYZIUJOTUUNY-MRXNPFEDSA-N 0.000 description 2
- CTLOSZHDGZLOQE-UHFFFAOYSA-N 14-methoxy-9-[(4-methylpiperazin-1-yl)methyl]-9,19-diazapentacyclo[10.7.0.02,6.07,11.013,18]nonadeca-1(12),2(6),7(11),13(18),14,16-hexaene-8,10-dione Chemical compound O=C1C2=C3C=4C(OC)=CC=CC=4NC3=C3CCCC3=C2C(=O)N1CN1CCN(C)CC1 CTLOSZHDGZLOQE-UHFFFAOYSA-N 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 201000004384 Alopecia Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 206010065553 Bone marrow failure Diseases 0.000 description 2
- 101100407084 Caenorhabditis elegans parp-2 gene Proteins 0.000 description 2
- 102000011727 Caspases Human genes 0.000 description 2
- 108010076667 Caspases Proteins 0.000 description 2
- 206010009244 Claustrophobia Diseases 0.000 description 2
- 206010053138 Congenital aplastic anaemia Diseases 0.000 description 2
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 2
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- 206010013700 Drug hypersensitivity Diseases 0.000 description 2
- 108090000371 Esterases Proteins 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- 208000013452 Fallopian tube neoplasm Diseases 0.000 description 2
- 201000004939 Fanconi anemia Diseases 0.000 description 2
- 102000001554 Hemoglobins Human genes 0.000 description 2
- 108010054147 Hemoglobins Proteins 0.000 description 2
- 101001113440 Homo sapiens Poly [ADP-ribose] polymerase 2 Proteins 0.000 description 2
- 208000019025 Hypokalemia Diseases 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- 108010044467 Isoenzymes Proteins 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 102100023652 Poly [ADP-ribose] polymerase 2 Human genes 0.000 description 2
- 102100037664 Poly [ADP-ribose] polymerase tankyrase-1 Human genes 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- SSJQVDUAKDRWTA-CAYKMONMSA-N SN38 glucuronide Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1O[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O SSJQVDUAKDRWTA-CAYKMONMSA-N 0.000 description 2
- 229940124639 Selective inhibitor Drugs 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- 231100000360 alopecia Toxicity 0.000 description 2
- 238000013103 analytical ultracentrifugation Methods 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
- 239000002111 antiemetic agent Substances 0.000 description 2
- 229940034982 antineoplastic agent Drugs 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 238000011284 combination treatment Methods 0.000 description 2
- 239000002872 contrast media Substances 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000002405 diagnostic procedure Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 210000003780 hair follicle Anatomy 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 231100000171 higher toxicity Toxicity 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 229950002133 iniparib Drugs 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- WTFXARWRTYJXII-UHFFFAOYSA-N iron(2+);iron(3+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[O-2].[Fe+2].[Fe+3].[Fe+3] WTFXARWRTYJXII-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 231100000225 lethality Toxicity 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- CXHHBNMLPJOKQD-UHFFFAOYSA-N methyl hydrogen carbonate Chemical compound COC(O)=O CXHHBNMLPJOKQD-UHFFFAOYSA-N 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 208000019899 phobic disease Diseases 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 208000024896 potassium deficiency disease Diseases 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 239000000092 prognostic biomarker Substances 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000036325 urinary excretion Effects 0.000 description 2
- 208000024719 uterine cervix neoplasm Diseases 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- MZAGXDHQGXUDDX-JSRXJHBZSA-N (e,2z)-4-ethyl-2-hydroxyimino-5-nitrohex-3-enamide Chemical compound [O-][N+](=O)C(C)C(/CC)=C/C(=N/O)/C(N)=O MZAGXDHQGXUDDX-JSRXJHBZSA-N 0.000 description 1
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 1
- QDVBKXJMLILLLB-UHFFFAOYSA-N 1,4'-bipiperidine Chemical compound C1CCCCN1C1CCNCC1 QDVBKXJMLILLLB-UHFFFAOYSA-N 0.000 description 1
- JNAHVYVRKWKWKQ-UHFFFAOYSA-N 2-(2-methyl-2-pyrrolidinyl)-1H-benzimidazole-4-carboxamide Chemical compound N=1C2=C(C(N)=O)C=CC=C2NC=1C1(C)CCCN1 JNAHVYVRKWKWKQ-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-UHFFFAOYSA-N 2-aminohexanoic acid Chemical compound CCCCC(N)C(O)=O LRQKBLKVPFOOQJ-UHFFFAOYSA-N 0.000 description 1
- HIWVLHPKZNBSBE-OUKQBFOZSA-N 4-[5-[(e)-2-[4-(2-chlorophenyl)-5-(5-methylsulfonylpyridin-2-yl)-1,2,4-triazol-3-yl]ethenyl]-1,3,4-oxadiazol-2-yl]benzonitrile Chemical compound N1=CC(S(=O)(=O)C)=CC=C1C(N1C=2C(=CC=CC=2)Cl)=NN=C1\C=C\C1=NN=C(C=2C=CC(=CC=2)C#N)O1 HIWVLHPKZNBSBE-OUKQBFOZSA-N 0.000 description 1
- JJWMRRNGWSITSQ-UHFFFAOYSA-N 5-phenacyloxy-2h-isoquinolin-1-one Chemical compound C=1C=CC(C(NC=C2)=O)=C2C=1OCC(=O)C1=CC=CC=C1 JJWMRRNGWSITSQ-UHFFFAOYSA-N 0.000 description 1
- 102100028161 ATP-binding cassette sub-family C member 2 Human genes 0.000 description 1
- 208000036832 Adenocarcinoma of ovary Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 102000002804 Ataxia Telangiectasia Mutated Proteins Human genes 0.000 description 1
- 108700040618 BRCA1 Genes Proteins 0.000 description 1
- 108700010154 BRCA2 Genes Proteins 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- 229960005529 CRLX101 Drugs 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 108010076525 DNA Repair Enzymes Proteins 0.000 description 1
- 102000011724 DNA Repair Enzymes Human genes 0.000 description 1
- 108090000323 DNA Topoisomerases Proteins 0.000 description 1
- 102000003915 DNA Topoisomerases Human genes 0.000 description 1
- 102100034483 DNA repair protein RAD51 homolog 4 Human genes 0.000 description 1
- 231100001074 DNA strand break Toxicity 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 201000001342 Fallopian tube cancer Diseases 0.000 description 1
- 102000008857 Ferritin Human genes 0.000 description 1
- 108050000784 Ferritin Proteins 0.000 description 1
- 238000008416 Ferritin Methods 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 206010071602 Genetic polymorphism Diseases 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 101000745711 Homo sapiens Cytochrome P450 3A4 Proteins 0.000 description 1
- 101001132266 Homo sapiens DNA repair protein RAD51 homolog 4 Proteins 0.000 description 1
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 1
- 101000581326 Homo sapiens Mediator of DNA damage checkpoint protein 1 Proteins 0.000 description 1
- 101000663006 Homo sapiens Poly [ADP-ribose] polymerase tankyrase-1 Proteins 0.000 description 1
- 101000589450 Homo sapiens Poly(ADP-ribose) glycohydrolase Proteins 0.000 description 1
- 208000029422 Hypernatremia Diseases 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 206010025327 Lymphopenia Diseases 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 102100027643 Mediator of DNA damage checkpoint protein 1 Human genes 0.000 description 1
- 108010066419 Multidrug Resistance-Associated Protein 2 Proteins 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 206010052399 Neuroendocrine tumour Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030124 Oedema peripheral Diseases 0.000 description 1
- 206010061328 Ovarian epithelial cancer Diseases 0.000 description 1
- 229940125941 PARP1/2 inhibitor Drugs 0.000 description 1
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 description 1
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 101710129670 Poly [ADP-ribose] polymerase tankyrase-1 Proteins 0.000 description 1
- 102100032347 Poly(ADP-ribose) glycohydrolase Human genes 0.000 description 1
- 108091026813 Poly(ADPribose) Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 102000000477 Sirtuin 2 Human genes 0.000 description 1
- 108010041216 Sirtuin 2 Proteins 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 229940124149 Tankyrase inhibitor Drugs 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 238000008050 Total Bilirubin Reagent Methods 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010047924 Wheezing Diseases 0.000 description 1
- BCPSLKYBXGKPIW-RTXWKGGWSA-N [(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl] 4-piperidin-1-ylpiperidine-1-carboxylate [(2R,3R,4S,5R,6R)-2-[(2S,3S,4R,5R)-3,4-disulfooxy-2,5-bis(sulfooxymethyl)oxolan-2-yl]oxy-3,5-disulfooxy-6-(sulfooxymethyl)oxan-4-yl] hydrogen sulfate Chemical class C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1.OS(=O)(=O)O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](COS(=O)(=O)O)O[C@@]1(COS(O)(=O)=O)O[C@@H]1[C@H](OS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@@H](COS(O)(=O)=O)O1 BCPSLKYBXGKPIW-RTXWKGGWSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000001142 anti-diarrhea Effects 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229940088954 camptosar Drugs 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 201000001343 fallopian tube carcinoma Diseases 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 229940096892 ferumoxytol injection Drugs 0.000 description 1
- 230000027950 fever generation Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 230000023611 glucuronidation Effects 0.000 description 1
- 229930182480 glucuronide Natural products 0.000 description 1
- 150000008134 glucuronides Chemical class 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 231100000226 haematotoxicity Toxicity 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 102000044284 human CYP3A4 Human genes 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- FMFIFGLHVOZDEL-UHFFFAOYSA-N indotecan Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2C=2C(=O)C3=CC=4OCOC=4C=C3C=2N1CCCN1CCOCC1 FMFIFGLHVOZDEL-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229940096010 iron polysaccharide Drugs 0.000 description 1
- MVZXTUSAYBWAAM-UHFFFAOYSA-N iron;sulfuric acid Chemical compound [Fe].OS(O)(=O)=O MVZXTUSAYBWAAM-UHFFFAOYSA-N 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 229960001571 loperamide Drugs 0.000 description 1
- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 1
- RVFGKBWWUQOIOU-NDEPHWFRSA-N lurtotecan Chemical compound O=C([C@]1(O)CC)OCC(C(N2CC3=4)=O)=C1C=C2C3=NC1=CC=2OCCOC=2C=C1C=4CN1CCN(C)CC1 RVFGKBWWUQOIOU-NDEPHWFRSA-N 0.000 description 1
- 229950002654 lurtotecan Drugs 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 229940100352 lynparza Drugs 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 108010082117 matrigel Proteins 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 208000037819 metastatic cancer Diseases 0.000 description 1
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 208000016065 neuroendocrine neoplasm Diseases 0.000 description 1
- 201000011519 neuroendocrine tumor Diseases 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229940127084 other anti-cancer agent Drugs 0.000 description 1
- 229960003552 other antineoplastic agent in atc Drugs 0.000 description 1
- 208000013371 ovarian adenocarcinoma Diseases 0.000 description 1
- 201000006588 ovary adenocarcinoma Diseases 0.000 description 1
- 208000021010 pancreatic neuroendocrine tumor Diseases 0.000 description 1
- 210000004197 pelvis Anatomy 0.000 description 1
- 201000002628 peritoneum cancer Diseases 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000011240 pooled analysis Methods 0.000 description 1
- 238000009258 post-therapy Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- GCILEJUNEYIABW-UHFFFAOYSA-N v5t7s4hp8a Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2C=2C(=O)C3=CC=4OCOC=4C=C3C=2N1CCCN1C=CN=C1 GCILEJUNEYIABW-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000012447 xenograft mouse model Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/04—Nitro compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/502—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dispersion Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (13)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562207709P | 2015-08-20 | 2015-08-20 | |
| US201562207760P | 2015-08-20 | 2015-08-20 | |
| US62/207,760 | 2015-08-20 | ||
| US62/207,709 | 2015-08-20 | ||
| US201562269756P | 2015-12-18 | 2015-12-18 | |
| US201562269511P | 2015-12-18 | 2015-12-18 | |
| US62/269,756 | 2015-12-18 | ||
| US62/269,511 | 2015-12-18 | ||
| US201662308924P | 2016-03-16 | 2016-03-16 | |
| US62/308,924 | 2016-03-16 | ||
| US201662323422P | 2016-04-15 | 2016-04-15 | |
| US62/323,422 | 2016-04-15 | ||
| PCT/US2016/047814 WO2017031442A1 (en) | 2015-08-20 | 2016-08-19 | Combination therapy using liposomal irinotecan and a parp inhibitor for cancer treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2992789A1 true CA2992789A1 (en) | 2017-02-23 |
Family
ID=56801880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2992789A Pending CA2992789A1 (en) | 2015-08-20 | 2016-08-19 | Combination therapy using liposomal irinotecan and a parp inhibitor for cancer treatment |
Country Status (18)
| Country | Link |
|---|---|
| US (4) | US9895365B2 (enExample) |
| EP (1) | EP3337467B1 (enExample) |
| JP (1) | JP7042739B2 (enExample) |
| KR (1) | KR20180037210A (enExample) |
| CN (1) | CN108348480A (enExample) |
| AU (1) | AU2016309002B2 (enExample) |
| CA (1) | CA2992789A1 (enExample) |
| ES (1) | ES2848118T3 (enExample) |
| HK (1) | HK1257216A1 (enExample) |
| IL (1) | IL257147B (enExample) |
| MX (1) | MX381475B (enExample) |
| PL (1) | PL3337467T3 (enExample) |
| PT (1) | PT3337467T (enExample) |
| RU (1) | RU2760185C2 (enExample) |
| SG (1) | SG10201913073YA (enExample) |
| SI (1) | SI3337467T1 (enExample) |
| TW (1) | TWI724018B (enExample) |
| WO (2) | WO2017031442A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2424792C2 (ru) | 2004-05-03 | 2011-07-27 | Хермес Байесайенсиз, Инк. | Липосомы, используемые для доставки лекарственных средств |
| AU2013202947B2 (en) | 2012-06-13 | 2016-06-02 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan |
| US9717724B2 (en) | 2012-06-13 | 2017-08-01 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies |
| JP7113619B2 (ja) * | 2014-12-09 | 2022-08-05 | イプセン バイオファーム リミティド | リポソーマルイリノテカンによる乳がんの治療 |
| US11318131B2 (en) | 2015-05-18 | 2022-05-03 | Ipsen Biopharm Ltd. | Nanoliposomal irinotecan for use in treating small cell lung cancer |
| HK1257216A1 (zh) | 2015-08-20 | 2019-10-18 | 益普生生物制药有限公司 | 使用脂质体伊立替康和parp抑制剂用於癌症治疗的组合疗法 |
| BR112018002941B1 (pt) | 2015-08-21 | 2023-12-05 | Ipsen Biopharm Ltd | Uso de irinotecano lipossomal, oxaliplatina, leucovorina e 5- fluorouracil no tratamento de primeira linha de adenocarcinoma metastático do pâncreas |
| BR112018006922B1 (pt) | 2015-10-16 | 2023-11-21 | Ipsen Biopharm Ltd | Composições de irinotecano lipossômico estabilizado para armazenamento |
| CN110402163A (zh) | 2016-11-02 | 2019-11-01 | 易普森生物制药有限公司 | 使用包括脂质体伊立替康、奥沙利铂、5-氟尿嘧啶(和甲酰四氢叶酸)的组合疗法治疗胃癌 |
| TWI879716B (zh) * | 2017-05-09 | 2025-04-11 | 美商提薩羅有限公司 | 治療癌症的組合療法 |
| MA49144A (fr) | 2017-05-18 | 2020-03-25 | Tesaro Inc | Polythérapies pour le traitement du cancer |
| GB201709076D0 (en) * | 2017-06-07 | 2017-07-19 | Inst Of Cancer Research: Royal Cancer Hospital | Parp inhibitors for use in methods of treating cancer |
| CA3076515A1 (en) | 2017-09-30 | 2019-04-04 | Tesaro, Inc. | Combination therapies for treating cancer |
| MA50618A (fr) | 2017-10-06 | 2020-08-12 | Tesaro Inc | Polyrhérapies et leurs utilisations |
| KR20200085307A (ko) * | 2017-11-04 | 2020-07-14 | 아라바이브 바이올로직스, 인크. | Axl 유인 수용체를 이용한 전이성 암의 치료 방법 |
| CA3087628A1 (en) * | 2018-01-12 | 2019-07-18 | Prolynx Llc | Synergistic cancer treatment |
| US20210030680A1 (en) * | 2018-04-13 | 2021-02-04 | The Board Of Regents Of University Of Texas System | Nanoparticle compositions and methods of use of parp inhibitor for treatment of cancer |
| CN112292133A (zh) * | 2018-06-01 | 2021-01-29 | 百济神州有限公司 | 在胃癌治疗中的parp抑制剂维持疗法 |
| WO2020124070A1 (en) * | 2018-12-14 | 2020-06-18 | Athenex HK Innovative Limited | Therapeutic combinations of orally administered irinotecan and a p-gp inhibitor for the treatment of cancer |
| CN114053415B (zh) * | 2020-07-30 | 2024-06-18 | 江苏天士力帝益药业有限公司 | Tsl-1502复方药物组合 |
| CN114053271B (zh) * | 2020-07-30 | 2024-05-07 | 江苏天士力帝益药业有限公司 | 一种含有tsl-1502m的药物组合物及其应用 |
| US20240252454A1 (en) * | 2021-05-03 | 2024-08-01 | Lead Discovery Center Gmbh | Composition comprising an inhibitor of mitochondrial transcription |
| RU2769543C2 (ru) * | 2021-07-21 | 2022-04-01 | Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр радиологии" Министерства здравоохранения Российской Федерации (ФГБУ "НМИЦ радиологии" Минздрава России) | Способ оценки первичного ответа на проводимую комбинированную химиотерапию спорадического рака яичников III и IV стадий |
| CN114259569B (zh) * | 2021-12-30 | 2024-02-27 | 中山大学附属第八医院（深圳福田） | 基于伊立替康和尼拉帕利的超分子纳米药物的制备方法和应用 |
| EP4209217A1 (en) * | 2022-01-11 | 2023-07-12 | Fundación Profesor Novoa Santos | Method for the treatment of brca1/2 mutated cancer |
| JPWO2024111564A1 (enExample) | 2022-11-21 | 2024-05-30 |
Family Cites Families (93)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6019790A (ja) | 1983-07-14 | 1985-01-31 | Yakult Honsha Co Ltd | 新規なカンプトテシン誘導体 |
| US5077056A (en) | 1984-08-08 | 1991-12-31 | The Liposome Company, Inc. | Encapsulation of antineoplastic agents in liposomes |
| JPH0720857B2 (ja) | 1988-08-11 | 1995-03-08 | テルモ株式会社 | リポソームおよびその製法 |
| IL91664A (en) | 1988-09-28 | 1993-05-13 | Yissum Res Dev Co | Ammonium transmembrane gradient system for efficient loading of liposomes with amphipathic drugs and their controlled release |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5538954A (en) | 1994-06-24 | 1996-07-23 | A/S Dumex (Dumex Ltd.) | Salts of tetracyclines |
| US5783568A (en) | 1994-06-10 | 1998-07-21 | Sugen, Inc. | Methods for treating cancer and other cell proliferative diseases |
| US5543152A (en) | 1994-06-20 | 1996-08-06 | Inex Pharmaceuticals Corporation | Sphingosomes for enhanced drug delivery |
| US6214388B1 (en) | 1994-11-09 | 2001-04-10 | The Regents Of The University Of California | Immunoliposomes that optimize internalization into target cells |
| US5800833A (en) | 1995-02-27 | 1998-09-01 | University Of British Columbia | Method for loading lipid vesicles |
| DE19605024A1 (de) | 1996-01-31 | 1997-08-07 | Schering Ag | Neue selektive Taxane, Verfahren zu ihrer Herstellung und ihre pharmazeutische Verwendung |
| US5997899A (en) | 1996-10-01 | 1999-12-07 | Skyepharma Inc. | Method for producing liposomes with increased percent of compound encapsulated |
| EP0949906A4 (en) | 1996-10-22 | 2004-11-24 | Hermes Biosciences Inc | LIPOSOMES LOADED WITH ACTIVE SUBSTANCE AND THEIR PRODUCTION METHOD |
| US6210707B1 (en) | 1996-11-12 | 2001-04-03 | The Regents Of The University Of California | Methods of forming protein-linked lipidic microparticles, and compositions thereof |
| US6787132B1 (en) | 1997-12-04 | 2004-09-07 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Combined chemo-immunotherapy with liposomal drugs and cytokines |
| US7244826B1 (en) | 1998-04-24 | 2007-07-17 | The Regents Of The University Of California | Internalizing ERB2 antibodies |
| US6726925B1 (en) | 1998-06-18 | 2004-04-27 | Duke University | Temperature-sensitive liposomal formulation |
| CA2346879A1 (en) | 1998-09-16 | 2000-04-27 | Alza Corporation | Liposome-entrapped topoisomerase inhibitors |
| US7311924B2 (en) | 1999-04-01 | 2007-12-25 | Hana Biosciences, Inc. | Compositions and methods for treating cancer |
| WO2000066125A1 (en) | 1999-04-29 | 2000-11-09 | Aventis Pharma S.A. | Method for treating cancer using camptothecin derivatives and 5-fluorouracil |
| US6720001B2 (en) | 1999-10-18 | 2004-04-13 | Lipocine, Inc. | Emulsion compositions for polyfunctional active ingredients |
| US6511676B1 (en) | 1999-11-05 | 2003-01-28 | Teni Boulikas | Therapy for human cancers using cisplatin and other drugs or genes encapsulated into liposomes |
| ATE341310T1 (de) | 2000-02-04 | 2006-10-15 | Lipoxen Technologies Ltd | Dehydratisierungs-/rehydratisierungsverfahren zur herstellung von liposome |
| US6545010B2 (en) | 2000-03-17 | 2003-04-08 | Aventis Pharma S.A. | Composition comprising camptothecin or a camptothecin derivative and a platin derivative for the treatment of cancer |
| JP4679028B2 (ja) | 2000-05-15 | 2011-04-27 | セルジーン コーポレイション | 結腸直腸癌を治療するための組成物および方法 |
| AU7038501A (en) | 2000-06-30 | 2002-01-14 | Inex Pharmaceuticals Corp | Liposomal antineoplastic drugs and uses thereof |
| TWI283575B (en) | 2000-10-31 | 2007-07-11 | Eisai Co Ltd | Medicinal compositions for concomitant use as anticancer agent |
| JP2004525138A (ja) | 2001-03-26 | 2004-08-19 | アルザ・コーポレーシヨン | 治療剤の改良された細胞内送達のためのリポソーム組成物 |
| US7219016B2 (en) | 2001-04-20 | 2007-05-15 | Yale University | Systems and methods for automated analysis of cells and tissues |
| WO2003030864A1 (en) | 2001-05-29 | 2003-04-17 | Neopharm, Inc. | Liposomal formulation of irinotecan |
| JP2005504759A (ja) | 2001-07-23 | 2005-02-17 | エピダウロス・バイオテクノロジー・アクチェンゲゼルシャフト | Ｃｙｐ３ａ５に基づいたがんの改善治療の手段及び方法 |
| US7850990B2 (en) | 2001-10-03 | 2010-12-14 | Celator Pharmaceuticals, Inc. | Compositions for delivery of drug combinations |
| AU2003237864B2 (en) | 2002-05-15 | 2008-12-18 | California Pacific Medical Center | Delivery of nucleic acid-like compounds |
| WO2003101475A1 (en) | 2002-05-31 | 2003-12-11 | Transmolecular Inc. | Treatment of cell proliferative disorders with chlorotoxin |
| WO2004035032A2 (en) | 2002-08-20 | 2004-04-29 | Neopharm, Inc. | Pharmaceutical formulations of camptothecine derivatives |
| RS20150135A1 (sr) | 2003-05-30 | 2015-08-31 | Genentech Inc. | Tretman sa anti-vegf antitelima |
| US8658203B2 (en) | 2004-05-03 | 2014-02-25 | Merrimack Pharmaceuticals, Inc. | Liposomes useful for drug delivery to the brain |
| RU2424792C2 (ru) | 2004-05-03 | 2011-07-27 | Хермес Байесайенсиз, Инк. | Липосомы, используемые для доставки лекарственных средств |
| AP2255A (en) | 2004-06-01 | 2011-07-21 | Yakult Honsha Kk | Irinotecan preparation. |
| JP2006248978A (ja) | 2005-03-10 | 2006-09-21 | Mebiopharm Co Ltd | 新規なリポソーム製剤 |
| TWI375673B (en) | 2005-04-11 | 2012-11-01 | Abbott Lab | 1h-benzimidazole-4-carboxamides substituted with a quaternary carbon at the 2-position are potent parp inhibitors |
| EP1951239A2 (en) | 2005-10-25 | 2008-08-06 | Celator Pharmaceuticals, Inc. | Fixed ratio drug combination treatments for solid tumors |
| WO2007076117A2 (en) | 2005-12-22 | 2007-07-05 | Celator Pharmaceuticals, Inc. | Liposomal formulations comprising secondary and tertiary amines and methods for preparing thereof |
| PL2338487T3 (pl) | 2006-01-17 | 2014-03-31 | Abbvie Bahamas Ltd | Terapia skojarzona z inhibitorami PARP |
| US20080146638A1 (en) | 2006-01-17 | 2008-06-19 | Abbott Laboratories | Combination therapy with parp inhibitors |
| WO2007109184A2 (en) | 2006-03-16 | 2007-09-27 | Bionumerik Pharmaceuticals, Inc. | Anti-cancer activity augmentation compounds and formulations and methods of use thereof |
| HRP20131113T1 (hr) | 2007-02-16 | 2014-01-17 | Merrimack Pharmaceuticals, Inc. | Protutijela protiv erbb3 i njihova uporaba |
| WO2008114274A1 (en) | 2007-03-19 | 2008-09-25 | Fresenius Kabi Onclology Ltd. | Proliposomal and liposomal compositions |
| US20120003160A1 (en) | 2007-06-29 | 2012-01-05 | Amag Pharmaceuticals, Inc. | Macrophage-Enhanced MRI (MEMRI) in a Single Imaging Session |
| ES2550759T3 (es) | 2007-08-17 | 2015-11-12 | Celator Pharmaceuticals, Inc. | Formulaciones farmacológicas de platino mejoradas |
| EP2197917A1 (en) | 2007-09-28 | 2010-06-23 | Universitätsspital Basel | Immunoliposomes for treatment of cancer |
| NZ586123A (en) | 2007-11-12 | 2012-12-21 | Bipar Sciences Inc | Treatment of ovarian cancer with 4-iodo-3-nitrobenzamide in combination with topoisomerase inhibitors |
| CA2708157A1 (en) | 2007-12-07 | 2009-06-11 | Bipar Sciences, Inc. | Treatment of cancer with combinations of topoisomerase inhibitors and parp inhibitors |
| US20110104256A1 (en) | 2008-03-25 | 2011-05-05 | Yaolin Wang | Methods for treating or preventing colorectal cancer |
| US8067432B2 (en) | 2008-03-31 | 2011-11-29 | University Of Kentucky Research Foundation | Liposomal, ring-opened camptothecins with prolonged, site-specific delivery of active drug to solid tumors |
| MX2010011145A (es) | 2008-04-11 | 2011-04-11 | Merrimack Pharmaceuticals Inc | Enlazadores de la albumina de suero humana y conjugados de la misma. |
| US8852630B2 (en) | 2008-05-13 | 2014-10-07 | Yale University | Chimeric small molecules for the recruitment of antibodies to cancer cells |
| CN102282168A (zh) | 2008-11-18 | 2011-12-14 | 梅里麦克制药股份有限公司 | 人血清白蛋白接头以及其结合物 |
| EP2413901A4 (en) | 2009-03-30 | 2015-05-06 | Cerulean Pharma Inc | POLYMER CONCRETE CONJUGATES, PARTICLES, COMPOSITIONS AND CORRESPONDING USES |
| JP2012525371A (ja) | 2009-05-01 | 2012-10-22 | オンコザイム・ファーマ・インコーポレイテッド | 癌を治療するためのペンタミジンの組み合わせ |
| JP5855568B2 (ja) | 2009-09-15 | 2016-02-09 | セルリアン・ファーマ・インコーポレイテッド | 癌の治療法 |
| ES2547698T3 (es) | 2009-12-03 | 2015-10-08 | Jiangsu Hengrui Medicine Co., Ltd. | Liposoma de irinotecán o su clorhidrato y método de preparación del mismo |
| EP2575804A4 (en) | 2010-06-04 | 2013-10-23 | Abraxis Bioscience Llc | METHOD FOR THE TREATMENT OF PANCREASCRE |
| CN107261110A (zh) | 2010-06-19 | 2017-10-20 | 健康科学西部大学 | Peg化脂质体包封的糖肽抗生素的新制剂 |
| EP2595618A1 (en) | 2010-07-19 | 2013-05-29 | BiPar Sciences, Inc. | Methods of treating breast cancer using 4-iodo-3-nitrobenzamide in combination with anti-tumor agents |
| CA2806076A1 (en) | 2010-07-22 | 2012-01-26 | The Regents Of The University Of California | Anti-tumor antigen antibodies and methods of use |
| RU2541100C2 (ru) | 2010-09-03 | 2015-02-10 | Боард Оф Регентс Оф Зе Юниверсити Оф Небраска | Способ и композиция для лечения рака |
| JP6208582B2 (ja) | 2010-12-06 | 2017-10-04 | メリマック ファーマシューティカルズ インコーポレーティッド | アントラサイクリン系化学療法剤を含有しているｅｒｂｂ２標的免疫リポソームによる治療における心臓毒性を抑制するための用量及び投与 |
| US9226984B2 (en) | 2010-12-14 | 2016-01-05 | Technical University of Denmark and Rigshospitalet | Entrapment of radionuclides in nanoparticle compositions |
| WO2012112730A2 (en) | 2011-02-15 | 2012-08-23 | Merrimack Pharmaceuticals, Inc. | Compositions and methods for delivering nucleic acid to a cell |
| HRP20170713T1 (hr) | 2011-04-19 | 2017-07-14 | Merrimack Pharmaceuticals, Inc. | Bispecifično anti-igf-1r i anti-erbb3 antitijelo |
| JO3283B1 (ar) | 2011-04-26 | 2018-09-16 | Sanofi Sa | تركيب يتضمن أفليبيرسيبت, حمض فولينيك, 5- فلورويوراسيل (5- Fu) وإرينوسيتان (FOLFIRI) |
| US8691231B2 (en) | 2011-06-03 | 2014-04-08 | Merrimack Pharmaceuticals, Inc. | Methods of treatment of tumors expressing predominantly high affinity EGFR ligands or tumors expressing predominantly low affinity EGFR ligands with monoclonal and oligoclonal anti-EGFR antibodies |
| AU2013201584A1 (en) | 2012-03-12 | 2013-09-26 | Merrimack Pharmaceuticals, Inc. | Methods for treating pancreatic cancer using combination therapies comprising an anti-ErbB3 antibody |
| WO2013158803A1 (en) | 2012-04-17 | 2013-10-24 | Merrimack Pharmaceuticals, Inc. | Compositions and methods for non-invasive imaging |
| US9717724B2 (en) | 2012-06-13 | 2017-08-01 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies |
| AU2013202947B2 (en) | 2012-06-13 | 2016-06-02 | Ipsen Biopharm Ltd. | Methods for treating pancreatic cancer using combination therapies comprising liposomal irinotecan |
| WO2014036470A1 (en) | 2012-08-31 | 2014-03-06 | Sloan-Kettering Institute For Cancer Research | Particles, methods and uses thereof |
| WO2014113167A1 (en) | 2012-12-14 | 2014-07-24 | Merrimack Pharmaceuticals, Inc. | Non-invasive imaging methods for patient selection for treatment with nanoparticulate therapeutic agents |
| UA117581C2 (uk) * | 2013-03-27 | 2018-08-27 | Тайхо Фармасьютікал Ко., Лтд. | Протипухлинний лікарський засіб, який включає низькодозований гідрохлориду іринотекану гідрат |
| WO2015031536A1 (en) | 2013-08-27 | 2015-03-05 | Northeastern University | Nanoparticle drug delivery system and method of treating cancer and neurotrauma |
| US20160303264A1 (en) | 2013-10-23 | 2016-10-20 | Merrimack Pharmaceuticals, Inc. | Liposomes useful for non-invasive imaging and drug delivery |
| JP7113619B2 (ja) | 2014-12-09 | 2022-08-05 | イプセン バイオファーム リミティド | リポソーマルイリノテカンによる乳がんの治療 |
| WO2016168451A1 (en) | 2015-04-14 | 2016-10-20 | Merrimack Pharmaceuticals, Inc. | Compositions for improving the pharmacokinetics and therapeutic index of cancer treatment |
| US11318131B2 (en) | 2015-05-18 | 2022-05-03 | Ipsen Biopharm Ltd. | Nanoliposomal irinotecan for use in treating small cell lung cancer |
| HK1257216A1 (zh) | 2015-08-20 | 2019-10-18 | 益普生生物制药有限公司 | 使用脂质体伊立替康和parp抑制剂用於癌症治疗的组合疗法 |
| BR112018002941B1 (pt) | 2015-08-21 | 2023-12-05 | Ipsen Biopharm Ltd | Uso de irinotecano lipossomal, oxaliplatina, leucovorina e 5- fluorouracil no tratamento de primeira linha de adenocarcinoma metastático do pâncreas |
| BR112018006922B1 (pt) | 2015-10-16 | 2023-11-21 | Ipsen Biopharm Ltd | Composições de irinotecano lipossômico estabilizado para armazenamento |
| US20170202840A1 (en) | 2016-01-14 | 2017-07-20 | Merrimack Pharmaceuticals, Inc. | Treatment of pancreatic cancer with liposomal irinotecan |
| WO2017172678A1 (en) | 2016-03-30 | 2017-10-05 | Merrimack Pharmaceuticals, Inc. | Methods for treating cancer using combination therapies comprising an oligoclonal anti-egfr antibody preparation and lipsomal irinotecan |
| US20170333421A1 (en) | 2016-05-18 | 2017-11-23 | Ipsen Biopharm Ltd. | Population Pharmacokinetics of Liposomal Irinotecan |
| MA45046A (fr) | 2016-05-18 | 2019-03-27 | Ipsen Biopharm Ltd | Irinotécan nanoliposomal utilisé dans le traitement du cancer bronchique à petites cellules |
| CN110402163A (zh) | 2016-11-02 | 2019-11-01 | 易普森生物制药有限公司 | 使用包括脂质体伊立替康、奥沙利铂、5-氟尿嘧啶(和甲酰四氢叶酸)的组合疗法治疗胃癌 |
-
2016
- 2016-08-19 HK HK18116219.1A patent/HK1257216A1/zh unknown
- 2016-08-19 TW TW105126680A patent/TWI724018B/zh active
- 2016-08-19 PL PL16757498T patent/PL3337467T3/pl unknown
- 2016-08-19 MX MX2018001659A patent/MX381475B/es unknown
- 2016-08-19 SG SG10201913073YA patent/SG10201913073YA/en unknown
- 2016-08-19 EP EP16757498.7A patent/EP3337467B1/en not_active Revoked
- 2016-08-19 WO PCT/US2016/047814 patent/WO2017031442A1/en not_active Ceased
- 2016-08-19 JP JP2018506592A patent/JP7042739B2/ja active Active
- 2016-08-19 WO PCT/US2016/047827 patent/WO2017031445A1/en not_active Ceased
- 2016-08-19 KR KR1020187004965A patent/KR20180037210A/ko not_active Ceased
- 2016-08-19 ES ES16757498T patent/ES2848118T3/es active Active
- 2016-08-19 CA CA2992789A patent/CA2992789A1/en active Pending
- 2016-08-19 SI SI201631023T patent/SI3337467T1/sl unknown
- 2016-08-19 PT PT167574987T patent/PT3337467T/pt unknown
- 2016-08-19 RU RU2018105655A patent/RU2760185C2/ru active
- 2016-08-19 CN CN201680046591.3A patent/CN108348480A/zh active Pending
- 2016-08-19 AU AU2016309002A patent/AU2016309002B2/en not_active Ceased
- 2016-10-28 US US15/337,274 patent/US9895365B2/en active Active
-
2017
- 2017-12-22 US US15/852,551 patent/US10478428B2/en active Active
-
2018
- 2018-01-25 IL IL257147A patent/IL257147B/en unknown
-
2019
- 2019-09-27 US US16/586,609 patent/US20200268742A1/en not_active Abandoned
-
2022
- 2022-03-24 US US17/703,312 patent/US11844795B2/en active Active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2016309002B2 (en) | Combination therapy using liposomal irinotecan and a PARP inhibitor for cancer treatment | |
| AU2016310476B8 (en) | Methods for treating metastatic pancreatic cancer using combination therapies comprising liposomal irinotecan and oxaliplatin | |
| AU2017354903A1 (en) | Treating gastric cancer using combination therapies comprising liposomal irinotecan, oxaliplatin, 5-fluoruracil (and leucovorin) | |
| WO2017172678A1 (en) | Methods for treating cancer using combination therapies comprising an oligoclonal anti-egfr antibody preparation and lipsomal irinotecan | |
| Saif et al. | Edotecarin: a novel topoisomerase I inhibitor | |
| CN111587115A (zh) | 协同癌症治疗 | |
| Koizumi et al. | Phase I/II study of bi-weekly irinotecan plus cisplatin in the treatment of advanced gastric cancer | |
| KR20240130081A (ko) | 항-trop-2 항체-약물 접합체와 추가 치료제의 병용 사용 | |
| Bowers et al. | Phase I study of oral cyclophosphamide and oral topotecan for children with recurrent or refractory solid tumors | |
| Sparreboom et al. | Topoisomerase I-targeting drugs | |
| Haglof et al. | Recent developments in the clinical activity of topoisomerase-1 inhibitors | |
| HK1257249B (en) | Combination therapy using liposomal irinotecan and a parp inhibitor for cancer treatment | |
| US20250381191A1 (en) | Methods for Treating Metastatic Pancreatic Cancer Using Combination Therapies Comprising Liposomal Irinotecan and Oxaliplatin | |
| Fracasso et al. | Phase I study of rubitecan and gemcitabine in patients with advanced malignancies | |
| Kawahara et al. | A phase i study of amrubicin and fixed dose of irinotecan (CPT-11) in relapsed small cell lung cancer: Japan multinational trial organization LC0303 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |
|
| EEER | Examination request |
Effective date: 20210819 |