NO315027B1 - Antitumor-preparater inneholdende taxan-derivater - Google Patents
Antitumor-preparater inneholdende taxan-derivater Download PDFInfo
- Publication number
- NO315027B1 NO315027B1 NO19951327A NO951327A NO315027B1 NO 315027 B1 NO315027 B1 NO 315027B1 NO 19951327 A NO19951327 A NO 19951327A NO 951327 A NO951327 A NO 951327A NO 315027 B1 NO315027 B1 NO 315027B1
- Authority
- NO
- Norway
- Prior art keywords
- esp
- combinations
- derivatives
- combination
- treatment
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 4
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 title abstract description 4
- 230000000259 anti-tumor effect Effects 0.000 title description 4
- 238000011282 treatment Methods 0.000 claims abstract description 16
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 13
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims abstract description 10
- 239000000126 substance Substances 0.000 claims abstract description 10
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 10
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims abstract description 8
- 229940122803 Vinca alkaloid Drugs 0.000 claims abstract description 7
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 7
- 229940100198 alkylating agent Drugs 0.000 claims abstract description 6
- 239000002168 alkylating agent Substances 0.000 claims abstract description 6
- 230000000340 anti-metabolite Effects 0.000 claims abstract description 6
- 229940100197 antimetabolite Drugs 0.000 claims abstract description 6
- 239000002256 antimetabolite Substances 0.000 claims abstract description 6
- 230000001613 neoplastic effect Effects 0.000 claims abstract description 6
- 229940063683 taxotere Drugs 0.000 claims abstract description 6
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 5
- 229960004397 cyclophosphamide Drugs 0.000 claims abstract description 5
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims abstract description 5
- 229960004679 doxorubicin Drugs 0.000 claims abstract description 5
- 229960005420 etoposide Drugs 0.000 claims abstract description 5
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims abstract description 5
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims abstract description 5
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229960004562 carboplatin Drugs 0.000 claims abstract description 4
- 190000008236 carboplatin Chemical compound 0.000 claims abstract description 4
- 229960002949 fluorouracil Drugs 0.000 claims abstract description 4
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan 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 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims abstract description 4
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 claims abstract description 4
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims abstract description 3
- SXFWKZNLYYRHMK-UHFFFAOYSA-N 1h-indolo[7,6-f]quinoline Chemical class C1=CC=C2C3=C(NC=C4)C4=CC=C3C=CC2=N1 SXFWKZNLYYRHMK-UHFFFAOYSA-N 0.000 claims abstract description 3
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims abstract description 3
- 108010006654 Bleomycin Proteins 0.000 claims abstract description 3
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims abstract description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims abstract description 3
- 229930192392 Mitomycin Natural products 0.000 claims abstract description 3
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims abstract description 3
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229960000473 altretamine Drugs 0.000 claims abstract description 3
- 230000003115 biocidal effect Effects 0.000 claims abstract description 3
- 229960001561 bleomycin Drugs 0.000 claims abstract description 3
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims abstract description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims abstract description 3
- 229960004316 cisplatin Drugs 0.000 claims abstract description 3
- 229960000684 cytarabine Drugs 0.000 claims abstract description 3
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims abstract description 3
- 229960000975 daunorubicin Drugs 0.000 claims abstract description 3
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229960000485 methotrexate Drugs 0.000 claims abstract description 3
- 229960004857 mitomycin Drugs 0.000 claims abstract description 3
- 229960001278 teniposide Drugs 0.000 claims abstract description 3
- 229960001196 thiotepa Drugs 0.000 claims abstract description 3
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229960001099 trimetrexate Drugs 0.000 claims abstract description 3
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims abstract 2
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims abstract 2
- 229940127093 camptothecin Drugs 0.000 claims abstract 2
- 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 claims abstract 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims abstract 2
- 229960001924 melphalan Drugs 0.000 claims abstract 2
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 229940088710 antibiotic agent Drugs 0.000 claims description 3
- 238000011319 anticancer therapy Methods 0.000 claims description 2
- 229940045687 antimetabolites folic acid analogs Drugs 0.000 claims description 2
- 230000003111 delayed effect Effects 0.000 claims description 2
- 150000002224 folic acids Chemical class 0.000 claims description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 2
- 229960001101 ifosfamide Drugs 0.000 claims description 2
- 229930012538 Paclitaxel Natural products 0.000 abstract description 8
- 229960001592 paclitaxel Drugs 0.000 abstract description 8
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 abstract description 8
- -1 ifosamide Chemical compound 0.000 abstract description 4
- 102000015696 Interleukins Human genes 0.000 abstract description 3
- 108010063738 Interleukins Proteins 0.000 abstract description 3
- 229940047122 interleukins Drugs 0.000 abstract description 3
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 abstract description 2
- 108010024976 Asparaginase Proteins 0.000 abstract description 2
- 108090000790 Enzymes Proteins 0.000 abstract description 2
- 102000004190 Enzymes Human genes 0.000 abstract description 2
- 102000014150 Interferons Human genes 0.000 abstract description 2
- 108010050904 Interferons Proteins 0.000 abstract description 2
- 229940088598 enzyme Drugs 0.000 abstract description 2
- 229960001842 estramustine Drugs 0.000 abstract description 2
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 abstract description 2
- 239000003102 growth factor Substances 0.000 abstract description 2
- 239000000367 immunologic factor Substances 0.000 abstract description 2
- 229940047124 interferons Drugs 0.000 abstract description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 abstract description 2
- 229960001156 mitoxantrone Drugs 0.000 abstract description 2
- 239000011149 active material Substances 0.000 abstract 1
- 229960003901 dacarbazine Drugs 0.000 abstract 1
- 239000003966 growth inhibitor Substances 0.000 abstract 1
- 230000003394 haemopoietic effect Effects 0.000 abstract 1
- 239000002574 poison Substances 0.000 abstract 1
- 231100000614 poison Toxicity 0.000 abstract 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 abstract 1
- 229960000624 procarbazine Drugs 0.000 abstract 1
- 229960000303 topotecan Drugs 0.000 abstract 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical class 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 abstract 1
- 206010028980 Neoplasm Diseases 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 12
- 230000000694 effects Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 231100000682 maximum tolerated dose Toxicity 0.000 description 4
- 206010006187 Breast cancer Diseases 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 208000012766 Growth delay Diseases 0.000 description 1
- 208000008342 Leukemia P388 Diseases 0.000 description 1
- 206010050017 Lung cancer metastatic Diseases 0.000 description 1
- SGDBTWWWUNNDEQ-UHFFFAOYSA-N Merphalan Chemical compound OC(=O)C(N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-UHFFFAOYSA-N 0.000 description 1
- 239000005662 Paraffin oil Substances 0.000 description 1
- 101710183280 Topoisomerase Proteins 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000000719 anti-leukaemic effect Effects 0.000 description 1
- 238000011394 anticancer treatment Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940045688 antineoplastic antimetabolites pyrimidine analogues Drugs 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000008274 breast adenocarcinoma Diseases 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 239000002636 mycotoxin Substances 0.000 description 1
- 229940086322 navelbine Drugs 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 229960001237 podophyllotoxin Drugs 0.000 description 1
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- 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
- A61K31/66—Phosphorus 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/243—Platinum; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/20—Interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/50—Hydrolases (3) acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D305/00—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms
- C07D305/14—Heterocyclic compounds containing four-membered rings having one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y305/00—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5)
- C12Y305/01—Hydrolases acting on carbon-nitrogen bonds, other than peptide bonds (3.5) in linear amides (3.5.1)
- C12Y305/01001—Asparaginase (3.5.1.1)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Foreliggende oppfinnelse angår kombinasjoner av taxol, Taxotére og deres analoger og terapeutiske stoffer som kan benyttes ved behandling av neoplastiske sykdommer.
Taxol, Taxotére og deres analoger, som oppviser interessante antitumorale og anti-leukemiske egenskaper, er spesielt brukbare ved behandling av ovarie-, bryst- eller lungekreft.
Fremstillingen av taxol, Taxotére og deres derivater er for eksempel gjenstand for de europeiske patenter EP 0 253 738 og EP 0 253 739 samt den internasjonale søknad PCT WO 9209589.
Generelt ligger de benyttede doser som avhenger av egne faktorer hos personen som behandles, mellom 1 og 10 mg/kg ved intraperitoneal administrering og mellom 1 og 3 ml/kg ved intravenøs administrering.
I en forsøksrapport fra University Hospital, Groningen, Holland, (van Putten et al.) er det vist at en kombinasjon av docetaxel (Taxotére) og carboplatin (et koordinasjons-kompleks av platina) gir en forbedret, terapeutisk virkning ved behandling av pasienter med ikke-småcellet lungecancer (NSCLC).
I en intern forsøksrapport fra Rhone-Poulenc Rorer S.A. (Bissery et al., 1996) er det vist at en kombinasjon av docetaxel (Taxotére) og irinotecan (en topoisomeraseinhibitor) oppviser en synergistisk virkning mot brystadenokarcinom.
I en erklæring av dr. A. Riva, inngitt den 21. august 1998, i forbindelse med US SN 08/967036, er det vist at en kombinasjon av Taxotére og doxorubicin (et antibiotikum) gir en synergistisk virkning ved behandling av pasienter med metastatisk lungecancer.
Det er nu funnet, og det er gjenstand for oppfinnelsen, at effektiviteten til taxol, Taxotére og deres analoger, betydelig kan forbedres når de administreres i forbindelse med minst et stoff som er terapeutisk brukbart ved anti-cancer-behandling med en virknings-mekanisme som er identisk med eller forskjellig fra den ti) taxan-derivatene.
Foreliggende oppfinnelse angår således kombinasjoner av Taxotére med minst ett terapeutisk stoff som er brukbart ved behandling av neoplastiske sykdommer, og disse kombinasjoner karakteriseres ved at det terapeutiske stoff er valgt blant alkyleringsmidler, antimetabolitter, vinca-alkaloider, épidofyllotoksiner, antibiotika, topoisome-
rase-inhibitorer og koordinasjonskomplekser av platina.
Blant de stoffer som kan benyttes i forbindelse med eller i kombinasjon med taxol, Taxotére og deres analoger, kan nevnes alkyleringsmidler som cyklofosfamid, ifosfamid, mefalan, heksametylmelamin, tiotépa eller dikarbacin, antimetabolitter, for eksempel pyrimidinanaloger som 5-fluoracil eller cytarabin eller dennes analoger som 2-fluor-desoksytidin eller folsyreanaloger som metotrexat, idatrexat eller trimetrexat, sopp-gifter, for eksempel vinca-alkaloider som vinblastin eller vincristin eller deres syntese-analoger som navelbin, eller estramustin eller taxoider, epidofilotoksiner som etopsid eller teniposid, antibiotika som daunorubicin, doxorubicin, bléomycin eller mitomycin, enzymer som L-asparaginase, topo-isomerase-inhibitorer som camptotécin-derivater valgt blant CPT-11 og topotécan eller pyridobenzoindol-derivater eller forskjellige midler som pro-carbacin, mitoxantron, koordinasjonskomplekser av platina som cis-platin eller carboplatin, biologisk respons-modifikatorer eller vekst-faktor-inhibitorer som interferoner eller inter-leukiner.
Aktiviteten til produktene avhenger av de benyttede doser og det er derfor mulig å benytte forhøyede doser og å øke aktiviteten mens man reduserer toksisitetsfenomenene eller forsinker deres opptreden i forbindelse med taxol, Taxotére, deres analoger eller deres kombinasjoner med andre terapeutisk aktive stoffer som vekst-faktorer av typen hématopoYetin-forbindelser som G-CSF eller GM-CSF eller visse interleukiner.
Kombinasjonene eller forbindelsene ifølge oppfinnelsen tillater å unngå eller å forsinke de pleiotropiske motstandsfenomener eller muskelmedikamentresistens-fenomenene.
Mere spesielt angår oppfinnelsen sambruk av taxol, Taxotére og deres analoger med vinca-alkaloider, cyklofosfamid, 5-fluoruracil, doxorubicin, cisplatin og étoposid.
Den forbedrede effektivitet av kombinasjonen ifølge oppfinnelsen kan påvises ved be-stemmelse av en terapeutisk synergisme.
Effektiviteten for en kombinasjon ifølge oppfinnelsen kan også karakteriseres ved en addisjon av virkningen av hver bestanddel.
En kombinasjon manifesterer en terapeutisk synergisme hvis den er terapeutisk over-legen den ene eller andre av bestanddelene benyttet ved sin optimale dose [T.H. Corbett et coil. "Cancer Treatment Reports", 66,1187 (1982)].
For å påvise effektiviteten for en kombinasjon kan det være nødvendig å sammenligne den tolererte maksimale dose for kombinasjonen med den tolererte maksimale dose for hver av bestanddelene isolert i det angjeldende studium. Denne effektivitet kan kvantifi-seres, for eksempel ved logiQ av cellene som drepes og som bestemmes i henhold til følgende formel:
der T - C betyr vekstforsinkelsen for cellene som er den midlere tid i dager for at tumorene i den behandlede gruppe (T) og tumorene fra sammenligningsgruppen (C) har nådd en på forhånd bestemt verdi (for eksempel 1 g) og Tj betyr tiden i dager som er nødven-dig for en dobling av tumor-volumet hos referansedyrene. [T.H. Corbett et coil. "Cancer", 40, 2660.2680 (1977); F.M. Schabel et coil., "Cancer Drug Development", Part B, "Methods in Cancer Research", 17,3-51, New York, Academic Press Inc. (1979)]. Et produkt anses som aktivt hvis log^o for de drepte celler er lik eller større enn 0,7. Et produkt anses som meget aktivt hvis logjø for de drepte celler er 2,8.
Kombinasjonen, benyttet i den egentlige maksimalt tolererte dose, der hver av bestanddelene er tilstede i en mengde generelt lik eller større enn den tolererte maksimale dose, manifesterer en terapeutisk synergi når logiø for drepte celler er større enn verdien for logio for drepte celler for den beste bestanddel når denne administreres alene.
Effektiviteten for kombinasjonene på faste tumorer kan bestemmes eksperimentelt på følgende måte: Dyrene som underkastes forsøkene, generelt mus, podes bilateralt, subkutant, med 30 til 60 mg av et fragment av en tumor på dag 0. Dyrene som bærer tumorene blandes før de underkastes forskjellige behandlinger og kontroller. Når det gjelder behandling av avan-serte tumorer lar man tumoren utvikle seg til den ønskede størrelse, dyr med utilstrekke-lig utviklede tumorer eller mineres. De valgte dyr fordeles vilkårlig for å underkaste dem kontroller og behandlinger. Dyr som ikke bærer tumorer kan likeledes underkastes de samme behandlinger som bærerdyrene for derved å kunne skille den toksiske virkning fra den egentlige virkning på tumoren. Kjemoterapien begynner vanligvis 3 til 22 dager efter poding i henhold til typen tumor og dyrene observeres hele dagen. De forskjellige dyregrupper veies 3 eller 4 ganger pr. uke inntil det maksimale vekt-tap er nådd hvorefter gruppene veies minst 1 gang pr. uke inntil slutten av prøven.
Tumorene måles to eller tre ganger pr. uke inntil tumoren har nådd ca. 2 gram eller inntil dyrets død hvis dette inntrer før tumoren når 2 gram. Dyrene underkastes autopsi efter avlivning. Den antitumorale aktivitet bestemmes som en funksjon av de forskjellige registrerte parametre.
For å studere kombinasjonene på leukemier blir dyrene podet med et bestemt antall celler og den antitumorale aktivitet bestemmes ved økningen av overlevelsestiden for mus som behandles i forhold til sammenligningsmus. Et produkt anses som aktivt hvis tids-økningen for overlevelse er over 27 % og det anses som meget aktivt hvis den er over 75 % når det gjelder leukemi P388.
Som eksempel gies i de følgende tabeller verdier som er oppnådd med kombinasjon av Taxotére og forskjellige kjemoterapeutiske midler som cyklofosfamid (alkyleringsmid-del), 5-fluor-uracil (antimetabolitt), étoposid (hemisyntesemiddel for podofyllotoksin) og vincristin (vinca-alkaloid) som benyttes i optimal dose. Foreliggende oppfinnelse angår også produkter inneholdende Taxotére og minst ett terapeutisk brukbart stoff som angitt ovenfor ved behandling av neoplastiske sykdommer som kombinasjonspreparater for en samtidig, separat eller tidsforskutt anvendelse ved anticancerterapi.
Produktene som utgjør kombinasjonen kan administreres samtidig, separat eller på tidsforskutt måte for å oppnå den maksimale kombinasjonseffektivitet; hver administrering kan ha en variabel varighet som tillater en hurtig total administrering ved kontinuerlig perfusjon.
Dette har ifølge oppfinnelsen som resultat at kombinasjonene ikke kun er begrenset til de som oppnås ved den fysiske sammenføring av bestanddelen men også den som tillater en separert administrering som kan være samtidig eller forskutt i tid.
Produktene ifølge oppfinnelsen er fortrinnsvis produkter som kan administreres parente-ralt. Imidlertid kan produktene administreres oralt eller inlraperetonealt når det gjelder loco-regionalc terapier.
Produktene for parenteral administrering cr generelt farmasøytisk godtagbare, sterile oppløsninger eller suspensjoner som eventuelt kan fremstille ekstermporalt på bruks-øyeblikket. For fremstilling av ikke-vandige oppløsninger eller suspensjoner kan man benytte naturlige, vegitabilske oljer som olivenolje, sesamolje eller paraffinolje eller injiserbare organiske estere som etyloleat. De vandige, sterile oppløsninger kan bestå av en oppløsning av produktet i vann. De vandige oppløsninger egner seg for intravenøs administrering hvis pH-verdien justeres riktig eller hvis det oppnås isotonisitet, for eksempel ved en tilstrekkelig mengde natriumklorid eller glucose. Steriliseringen kan gjennomføres ved oppvarming eller på en hvilken som helst annen måte som ikke end-rer preparatet. Kombinasjonen kan også foreligge i form av liposomer eller i form av en forbindelse med bærere som cyklodekstriner eller polyetylenglykoler.
Produktene for oral eller intraperetoneal-administrering er fortrinnsvis vandige oppløs-ninger eller suspensjoner.
I kombinasjonene ifølge oppfinnelsen der anvendelsen av bestanddelene kan være samtidig, separat eller forskutt i tid, er det særlig fordelaktig at mengden av taxan-derivat utgjør 10 til 90 vekt-% av kombinasjonen idet denne mengde kan variere som funksjo-nen av arten av det benyttede substrat, den tilsiktede effektivitet og typen av cancer som skal behandles.
Kombinasjonene ifølge oppfinnelsen er spesielt brukbare ved behandling av bryst-, ovarie- eller lungekreft. Spesielt kan de oppvise den fordel at de tillater bruk av bestanddelene ved lavere doser enn når de benyttes alene.
Det følgende eksempel skal illustrere oppfinnelsen.
Eksempel
På i og for seg kjent måte fremstilles, for intravenøs administrering, ampuller på 10 cm<3 >inneholdende 10 mg Taxotére.
Man fremstiller, på i og for seg kjent måte, for intravenøs administrering, ampuller på
5 cm3 inneholdende 100 mg étoposid.
Disse oppløsninger administreres samtidig, efter hensiktsmessig fortynning, ved perfusjon.
Behandlingen kan gjentas flere ganger pr. dag eller pr. uke inntil det er oppnådd en par-tiell eller total remisjon eller helbredelse.
Claims (10)
1.
Kombinasjoner av Taxotére med minst ett terapeutisk stoff som er brukbart ved behandling av neoplastiske sykdommer, karakterisert ved at det terapeutiske stoff er valgt blant alkyleringsmidler, antimetabolitter, vinca-alkaloider, épidofyllotoksiner, antibiotika, topoisomerase-inhibitorer og koordinasjonskomplekser av platina.
2.
Kombinasjon ifølge krav 1, karakterisert ved at alkyleringsmidlene er valgt blant cyklofosfamid, ifosfamid, melfalan, heksametylmelamin, tiotépa eller decarbazin.
3.
Kombinasjoner ifølge krav 1, karakterisert ved at antimetabolittene er valgt blant 5-fluoruracil, cytarabin og folsyreanaloger valgt blant métotrexat, idatrexat eller trimetrexat.
4.
Kombinasjoner ifølge krav 1, karakterisert ved at vinca-alkaloidene også omfatter deres syntetiske eller semisyntetiske analoger.
5.
Kombinasjon ifølge krav 1, karakterisert ved at epidofyllotoksinene er valgt blant etoposid og teniposid.
6.
Kombinasjoner ifølge krav 1, karakterisert ved at antibiotikumet er valgt blant daunorubicin, doxorubicin, bléomycin eller mitomycin.
7.
Kombinasjoner ifølge krav 1, karakterisert ved at topoisomerase-inhibitorene er valgt blant kamptotesin og derivater derav valgt blant CPT-11 og topotécan og derivater av pyridobenzoindol.
8.
Kombinasjon ifølge krav 1, karakterisert ved at koordinasjonskomplekser av platina er valgt blant cisplatin og carboplatin.
9.
Kombinasjoner ifølge et hvilket som helst av kravene 1 til 8, karakterisert ved at de inneholder 10 til 90 vekt-% Taxotére.
10.
Produkter inneholdende Taxotére og minst et terapeutisk brukbart stoff som angitt i et av kravene 1 til 9 ved behandling av neoplastiske sykdommer som kombinasjonspreparater for en samtidig, separat eller tidsforskutt anvendelse ved anticancerterapi.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9213525A FR2697752B1 (fr) | 1992-11-10 | 1992-11-10 | Compositions antitumorales contenant des dérivés du taxane. |
PCT/FR1993/001096 WO1994010995A1 (fr) | 1992-11-10 | 1993-11-08 | Compositions antitumorales contenant des derives du taxane |
Publications (3)
Publication Number | Publication Date |
---|---|
NO951327L NO951327L (no) | 1995-04-05 |
NO951327D0 NO951327D0 (no) | 1995-04-05 |
NO315027B1 true NO315027B1 (no) | 2003-06-30 |
Family
ID=9435406
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19951327A NO315027B1 (no) | 1992-11-10 | 1995-04-05 | Antitumor-preparater inneholdende taxan-derivater |
Country Status (25)
Country | Link |
---|---|
US (13) | US5728687A (no) |
EP (4) | EP0667771B1 (no) |
JP (1) | JP3974938B2 (no) |
KR (2) | KR100334051B1 (no) |
AT (2) | ATE205083T1 (no) |
AU (1) | AU680845B2 (no) |
CA (1) | CA2149055C (no) |
CZ (2) | CZ288033B6 (no) |
DE (2) | DE69318033T2 (no) |
DK (2) | DK0827745T3 (no) |
ES (2) | ES2163076T3 (no) |
FI (1) | FI952248A0 (no) |
FR (1) | FR2697752B1 (no) |
GR (2) | GR3026666T3 (no) |
HU (1) | HU223773B1 (no) |
MX (1) | MX9306924A (no) |
NO (1) | NO315027B1 (no) |
NZ (1) | NZ257585A (no) |
PL (1) | PL173951B1 (no) |
PT (1) | PT827745E (no) |
RU (1) | RU2131250C1 (no) |
SK (1) | SK282867B6 (no) |
TW (1) | TW386877B (no) |
WO (1) | WO1994010995A1 (no) |
ZA (1) | ZA938182B (no) |
Families Citing this family (128)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2686899B1 (fr) * | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
FR2697752B1 (fr) * | 1992-11-10 | 1995-04-14 | Rhone Poulenc Rorer Sa | Compositions antitumorales contenant des dérivés du taxane. |
FR2698871B1 (fr) | 1992-12-09 | 1995-02-24 | Rhone Poulenc Rorer Sa | Nouveau taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
US6441026B1 (en) | 1993-11-08 | 2002-08-27 | Aventis Pharma S.A. | Antitumor compositions containing taxane derivatives |
FR2729295A1 (fr) * | 1995-01-17 | 1996-07-19 | Rhone Poulenc Rorer Sa | Traitement therapeutique combine des pathologies hyperproliferatives |
US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
US6685940B2 (en) * | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
US6011069A (en) * | 1995-12-26 | 2000-01-04 | Nisshin Flour Milling Co., Ltd. | Multidrug resistance inhibitors |
US6096336A (en) * | 1996-01-30 | 2000-08-01 | The Stehlin Foundation For Cancer Research | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
US6667053B1 (en) * | 1996-02-16 | 2003-12-23 | Elan Pharmaceuticals, Inc. | D and L etherlipid stereoisomers and liposomes |
AU2195297A (en) * | 1996-02-20 | 1997-09-02 | Sloan-Kettering Institute For Cancer Research | Combinations of pkc inhibitors and therapeutic agents for treating cancers |
US6441025B2 (en) * | 1996-03-12 | 2002-08-27 | Pg-Txl Company, L.P. | Water soluble paclitaxel derivatives |
US7371376B1 (en) * | 1996-10-18 | 2008-05-13 | Genentech, Inc. | Anti-ErbB2 antibodies |
US5811452A (en) * | 1997-01-08 | 1998-09-22 | The Research Foundation Of State University Of New York | Taxoid reversal agents for drug-resistance in cancer chemotherapy and pharmaceutical compositions thereof |
US6103698A (en) * | 1997-03-13 | 2000-08-15 | Basf Aktiengesellschaft | Dolastatin-15 derivatives in combination with taxanes |
ZA9811162B (en) * | 1997-12-12 | 2000-06-07 | Genentech Inc | Treatment with anti-ERBB2 antibodies. |
US6740497B2 (en) * | 1998-03-06 | 2004-05-25 | The Regents Of The University Of California | Method and apparatus for detecting cancerous cells using molecules that change electrophoretic mobility |
US6335201B1 (en) * | 1998-03-06 | 2002-01-01 | The Regents Of The University Of California | Method and apparatus for detecting enzymatic activity using molecules that change electrophoretic mobility |
US6849616B1 (en) | 1998-03-27 | 2005-02-01 | Pharmacia Italia S.P.A. | Methods to potentiate intravenous estramustine phosphate |
AU750010B2 (en) * | 1998-03-27 | 2002-07-11 | Pharmacia & Upjohn Company | Methods to potentiate intravenous estramustine phosphate |
BR9909393A (pt) * | 1998-04-03 | 2000-12-26 | Ajinomoto Kk | Agente antitumor, uso de um derivado de estilbeno e um composto de coordenação de platina, e, processo para o tratamento ou melhoramento de um tumor |
AU3961899A (en) * | 1998-05-04 | 1999-11-23 | Auckland Uniservices Limited | Chemotherapeutic treatment |
TWI227136B (en) * | 1998-05-21 | 2005-02-01 | Smithkline Beecham Corp | Novel pharmaceutical composition for the prevention and/or treatment of cancer |
PT1100589E (pt) * | 1998-07-30 | 2005-05-31 | Sigma Tau Ind Farmaceuti | Utilizacao de propionil-l-carnitina e acetil-l-carnitina na preparacao de medicamentos com actividade anticancerigena |
GB9904386D0 (en) * | 1999-02-25 | 1999-04-21 | Pharmacia & Upjohn Spa | Antitumour synergistic composition |
US20050192360A1 (en) * | 1999-04-14 | 2005-09-01 | Li Chiang J. | Method of treatment of pancreatic cancer |
US20050222246A1 (en) * | 1999-04-14 | 2005-10-06 | Li Chiang J | Beta-lapachone is a broad spectrum anti-cancer agent |
DE60031268T2 (de) * | 1999-04-14 | 2007-05-24 | Dana-Farber Cancer Institute, Inc., Boston | Verfahren und zusammansetzung zur behandlung von krebs |
MY164077A (en) * | 1999-05-13 | 2017-11-30 | Pharma Mar Sa | Compositions and uses of et743 for treating cancer |
US6737240B1 (en) * | 1999-05-25 | 2004-05-18 | Rigel Pharmaceuticals, Inc. | Methods of screening for a multi-drug resistance conferring peptide |
US20030086924A1 (en) * | 1999-06-25 | 2003-05-08 | Genentech, Inc. | Treatment with anti-ErbB2 antibodies |
CA2383493C (en) * | 1999-06-25 | 2010-08-10 | Genentech, Inc. | Treating prostate cancer with anti-erbb2 antibodies |
US6949245B1 (en) * | 1999-06-25 | 2005-09-27 | Genentech, Inc. | Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies |
CH694589A5 (de) * | 1999-06-25 | 2005-04-15 | Genentech Inc | Humanisierte Anti-ErbB2-Antikörper und Behandlung mit Anti-ErbB2-Antikörpern. |
US20040013667A1 (en) * | 1999-06-25 | 2004-01-22 | Genentech, Inc. | Treatment with anti-ErbB2 antibodies |
US7041292B1 (en) | 1999-06-25 | 2006-05-09 | Genentech, Inc. | Treating prostate cancer with anti-ErbB2 antibodies |
US6352996B1 (en) | 1999-08-03 | 2002-03-05 | The Stehlin Foundation For Cancer Research | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
US6228855B1 (en) | 1999-08-03 | 2001-05-08 | The Stehlin Foundation For Cancer Research | Aromatic esters of camptothecins and methods to treat cancers |
NZ517150A (en) | 1999-08-27 | 2005-01-28 | Genentech Inc | Dosages for treatment with anti-ErbB2 antibodies |
AU775373B2 (en) | 1999-10-01 | 2004-07-29 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
GB9925127D0 (en) * | 1999-10-22 | 1999-12-22 | Pharmacia & Upjohn Spa | Oral formulations for anti-tumor compounds |
JP2003522171A (ja) | 2000-02-02 | 2003-07-22 | フロリダ・ステイト・ユニバーシティ・リサーチ・ファウンデイション・インコーポレイテッド | 抗腫瘍剤としてのc10カーボネート置換タキサン |
US6362217B2 (en) * | 2000-03-17 | 2002-03-26 | Bristol-Myers Squibb Company | Taxane anticancer agents |
AU2001266557A1 (en) * | 2000-04-12 | 2001-10-23 | Human Genome Sciences, Inc. | Albumin fusion proteins |
WO2001083781A2 (en) * | 2000-04-28 | 2001-11-08 | Millennium Pharmaceuticals, Inc. | 14094, a novel human trypsin family member and uses thereof |
MXPA02011319A (es) * | 2000-05-15 | 2003-06-06 | Pharma Mar Sa | Analogos antitumorales de ecteinascidina 743. |
DK1282443T3 (da) * | 2000-05-19 | 2010-01-04 | Genentech Inc | Gendetektionsassay til at forbedre sandsynligheden for et effektivt respons på en ErbB-antagonist cancerterapi |
US6541509B2 (en) * | 2000-09-15 | 2003-04-01 | Albert Einstein College Of Medicine Of Yeshiva University | Method for treating neoplasia using combination chemotherapy |
AU2001288805A1 (en) | 2000-09-22 | 2002-04-02 | Bristol-Myers Squibb Company | Method for reducing toxicity of combined chemotherapies |
AU1249902A (en) * | 2000-11-06 | 2002-05-15 | Pharma Mar Sa | Effective antitumour treatments |
US20050197405A1 (en) * | 2000-11-07 | 2005-09-08 | Li Chiang J. | Treatment of hematologic tumors and cancers with beta-lapachone, a broad spectrum anti-cancer agent |
US7115565B2 (en) | 2001-01-18 | 2006-10-03 | Pharmacia & Upjohn Company | Chemotherapeutic microemulsion compositions of paclitaxel with improved oral bioavailability |
RU2178702C1 (ru) * | 2001-02-21 | 2002-01-27 | Общество с ограниченной ответственностью "Нобель" | Антираковое средство |
US6703400B2 (en) * | 2001-02-23 | 2004-03-09 | Schering Corporation | Methods for treating multidrug resistance |
BR0207443A (pt) * | 2001-03-06 | 2004-04-06 | Bristol Myeres Squibb Company | Método e forma de dosagem para o tratamento de tumores pela administração de tegafur, uracila, ácido folìnico, paclitaxel e carboplatina |
ES2384789T3 (es) * | 2001-03-14 | 2012-07-12 | Bristol-Myers Squibb Company | Combinación de un análogo de epotilona y agentes quimioterapéuticos para el tratamiento de enfermedades proliferativas |
WO2002074246A2 (en) * | 2001-03-20 | 2002-09-26 | New Century Pharmaceuticals, Inc. | Method and compositions for optimizing blood and tissue stability of camptothecin and other albumin-binding therapeutic compounds |
UY27220A1 (es) * | 2001-03-23 | 2002-09-30 | Aventis Pharma Sa | Combinación de un taxano con una quinasa ciclina-dependiente |
CA2446739A1 (en) * | 2001-05-25 | 2002-12-05 | Human Genome Sciences, Inc. | Chemokine beta-1 fusion proteins |
TWI297335B (en) * | 2001-07-10 | 2008-06-01 | Synta Pharmaceuticals Corp | Taxol enhancer compounds |
US6924312B2 (en) | 2001-07-10 | 2005-08-02 | Synta Pharmaceuticals Corp. | Taxol enhancer compounds |
TWI332943B (en) * | 2001-07-10 | 2010-11-11 | Synta Pharmaceuticals Corp | Taxol enhancer compounds |
TWI252847B (en) | 2001-07-10 | 2006-04-11 | Synta Pharmaceuticals Corp | Synthesis of taxol enhancers |
EP1293205A1 (en) * | 2001-09-18 | 2003-03-19 | G2M Cancer Drugs AG | Valproic acid and derivatives thereof for the combination therapy of human cancers, for the treatment of tumour metastasis and minimal residual disease |
EP1435965A4 (en) * | 2001-09-26 | 2005-09-21 | Intermune Inc | PHARMACEUTICAL COMPOSITIONS AND METHOD FOR THE TREATMENT OF CANCER |
EP1435988A4 (en) * | 2001-10-19 | 2008-01-09 | Pharmamar Sa | IMPROVED USE OF ANTI-TUMORAL COMPOUND IN THE TREATMENT OF CANCER |
TW200408407A (en) * | 2001-11-30 | 2004-06-01 | Dana Farber Cancer Inst Inc | Methods and compositions for modulating the immune system and uses thereof |
EP2261250B1 (en) | 2001-12-21 | 2015-07-01 | Human Genome Sciences, Inc. | GCSF-Albumin fusion proteins |
WO2003059934A2 (en) * | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
GB0202544D0 (en) * | 2002-02-04 | 2002-03-20 | Pharma Mar Sa | The synthesis of naturally occuring ecteinascidins and related compounds |
US6816571B2 (en) * | 2002-02-06 | 2004-11-09 | L-3 Communications Security And Detection Systems Corporation Delaware | Method and apparatus for transmitting information about a target object between a prescanner and a CT scanner |
US7426479B2 (en) * | 2002-03-12 | 2008-09-16 | Ncr Corporation | Customer activity data system and method |
US6593334B1 (en) * | 2002-05-02 | 2003-07-15 | The University Of North Carolina At Chapel Hill | Camptothecin-taxoid conjugates as antimitotic and antitumor agents |
OA12819A (en) * | 2002-05-17 | 2006-07-10 | Aventis Pharma Sa | Use of docetaxel/doxorubicin/cyclophosphamide in adjuvant therapy of breast and ovarian cancer. |
AU2003254261B2 (en) * | 2002-07-30 | 2008-04-17 | Children's Medical Center Corporation | Compositions of ezetimibe and methods for the treatment of cholesterol-associated benign and malignant tumors |
EP1572972A4 (en) * | 2002-11-21 | 2007-11-21 | Genentech Inc | THERAPY OF NON-MALIGNER DISEASES OR DISORDER WITH ANTI-ERBB2 ANTIBODIES |
DE10254601A1 (de) | 2002-11-22 | 2004-06-03 | Ganymed Pharmaceuticals Ag | Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung |
TWI330079B (en) | 2003-01-15 | 2010-09-11 | Synta Pharmaceuticals Corp | Treatment for cancers |
US20040229931A1 (en) * | 2003-04-30 | 2004-11-18 | Aventis Pharma S. A. | 1-Aryl-3-(indol-5-yl) prop-2-en-1-ones, compositions containing them and use |
CA2526278A1 (en) * | 2003-05-20 | 2004-12-02 | Aronex Pharmaceuticals, Inc. | Combination chemotherapy comprising a liposomal platinum complex |
PE20050206A1 (es) * | 2003-05-26 | 2005-03-26 | Schering Ag | Composicion farmaceutica que contiene un inhibidor de histona deacetilasa |
GB0312407D0 (en) * | 2003-05-29 | 2003-07-02 | Pharma Mar Sau | Treatment |
GB0324201D0 (en) * | 2003-10-15 | 2003-11-19 | Pharma Mar Sau | Improved antitumoral combinations |
EP1689404B9 (en) * | 2003-11-13 | 2009-04-22 | Pharma Mar, S.A.U. | Combination of et-743 with 5-fluorouracil pro-drugs for the treatment of cancer |
EP1691809A1 (en) * | 2003-11-14 | 2006-08-23 | Pharma Mar, S.A. | Combination therapy comprising the use of et-743 and paclitaxel for treating cancer |
GB0326486D0 (en) * | 2003-11-14 | 2003-12-17 | Pharma Mar Sau | Combination treatment |
US20050187288A1 (en) * | 2004-02-20 | 2005-08-25 | Chiang Li | Beta-lapachone and methods of treating cancer |
EP1720574A4 (en) * | 2004-02-23 | 2009-09-09 | Sugen Inc | METHOD OF TREATING ABNORMAL CELL GROWTH USING C-MET AND M-TOR INHIBITORS |
US20050192247A1 (en) * | 2004-02-23 | 2005-09-01 | Li Chiang J. | Method of treating cancers |
CN1993318B (zh) | 2004-06-23 | 2012-10-03 | Synta医药公司 | 用于治疗癌症的双(硫代-酰肼酰胺)盐 |
US20080242670A2 (en) * | 2004-09-29 | 2008-10-02 | Pharma Mar S.A., Sociedad Unipersonal | Anti-Inflammatory Agents |
RS50822B (sr) * | 2004-10-26 | 2010-08-31 | Pharma Mar S.A., Sociedad Unipersonal | Pegilovani lipozomalni doksorubicin u kombinaciji sa ekteinescidinom 743 |
RU2382647C2 (ru) * | 2004-10-29 | 2010-02-27 | Фарма Мар С.А., Сосьедад Униперсональ | Композиции, содержащие эктинэсайдин и дисахарид |
JP5204489B2 (ja) | 2004-11-19 | 2013-06-05 | シンタ ファーマスーティカルズ コーポレイション | Hsp70発現を増加するためのビス(チオ‐ヒドラジドアミド) |
CN101083998A (zh) * | 2004-11-22 | 2007-12-05 | 王者制药研究发展有限公司 | 用腺苷a3受体激动剂强化治疗hif-1介导的病症 |
CN105288630A (zh) * | 2005-02-18 | 2016-02-03 | 阿布拉科斯生物科学有限公司 | 治疗剂的组合和给予方式以及联合治疗 |
EP2343320B1 (en) | 2005-03-25 | 2017-10-25 | GITR, Inc. | Anti-gitr antibodies and uses thereof |
JP2008536875A (ja) | 2005-04-15 | 2008-09-11 | シンタ ファーマシューティカルズ コーポレーション | ビス(チオヒドラジド)アミド化合物による併用癌療法 |
EP1888520A2 (en) | 2005-05-16 | 2008-02-20 | Synta Pharmaceuticals Corporation | Synthesis of bis(thio-hydrazide amide) salts |
CN103735560A (zh) * | 2005-06-07 | 2014-04-23 | 耶鲁大学 | 使用克来夫定和替比夫定治疗癌症和其它病症或疾病状态的方法 |
BRPI0614826A2 (pt) | 2005-08-16 | 2011-04-19 | Synta Pharmaceuticals Corp | composições, método para a preparação de liofilizado de uma composição e liofilizado |
US20070172844A1 (en) * | 2005-09-28 | 2007-07-26 | University Of South Florida | Individualized cancer treatments |
GB0522082D0 (en) * | 2005-10-31 | 2005-12-07 | Pharma Mar Sa | Formulations |
WO2007056118A1 (en) * | 2005-11-04 | 2007-05-18 | Wyeth | Antineoplastic combinations with mtor inhibitor, herceptin, and/or hki-272 |
US8404697B2 (en) | 2005-11-11 | 2013-03-26 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
WO2007104011A2 (en) * | 2006-03-08 | 2007-09-13 | University Of Maryland, Baltimore | Inhibition of microtubule protrusion in cancer cells |
MX2008014953A (es) * | 2006-05-26 | 2009-03-05 | Bayer Healthcare Llc | Combinaciones de medicamentos con diarilureas sustituidas para el tratamiento de cancer. |
AU2007288338B2 (en) | 2006-08-21 | 2012-05-03 | Synta Pharmaceuticals Corp. | Compounds for treating proliferative disorders |
EP2076254A2 (en) | 2006-08-31 | 2009-07-08 | Synta Pharmaceuticals Corporation | Combination with bis(thiohydrazide amides) for treating cancer |
US7645904B2 (en) | 2006-09-15 | 2010-01-12 | Synta Pharmaceuticals Corp. | Purification of bis(thiohydrazide amides) |
RU2492864C2 (ru) * | 2006-09-18 | 2013-09-20 | Бёрингер Ингельхайм Интернациональ Гмбх | Способ лечения рака, несущего мутации egfr |
FR2907341B1 (fr) * | 2006-10-18 | 2012-08-17 | Pf Medicament | Utilisation d'un anticorps anti-cd151 pour le traitement du cancer |
US20090093538A1 (en) * | 2007-01-03 | 2009-04-09 | Synta Pharmaceuticals Corp | Method for treating cancer |
ES2591281T3 (es) * | 2007-07-12 | 2016-11-25 | Gitr, Inc. | Terapias de combinación que emplean moléculas de enlazamiento a GITR |
JP2011500046A (ja) * | 2007-10-19 | 2011-01-06 | ファルマ・マール・ソシエダード・アノニマ | Et−743治療のための予後分子マーカー |
US9545381B2 (en) | 2009-07-06 | 2017-01-17 | Boehringer Ingelheim International Gmbh | Process for drying of BIBW2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient |
WO2013174403A1 (en) * | 2012-05-23 | 2013-11-28 | Ganymed Pharmaceuticals Ag | Combination therapy involving antibodies against claudin 18.2 for treatment of cancer |
JP6499079B2 (ja) | 2012-11-13 | 2019-04-10 | バイオエヌテック アーゲーBioNTech AG | クローディンを発現するガン疾患を処置するための剤 |
US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
PE20211798A1 (es) | 2014-03-21 | 2021-09-13 | Abbvie Inc | Anticuerpos y conjugados de anticuerpo y farmaco anti-egfr |
US10080807B2 (en) | 2014-06-09 | 2018-09-25 | Lipomedix Pharmaceuticals Ltd. | Combination chemotherapy comprising a liposomal prodrug of mitomycin C |
MX2018015272A (es) | 2016-06-08 | 2019-08-12 | Abbvie Inc | Anticuerpos anti-cd98 y conjugados de anticuerpo y farmaco. |
CN109562169A (zh) | 2016-06-08 | 2019-04-02 | 艾伯维公司 | 抗cd98抗体及抗体药物偶联物 |
JP2019521973A (ja) | 2016-06-08 | 2019-08-08 | アッヴィ・インコーポレイテッド | 抗bh7−h3抗体及び抗体薬物コンジュゲート |
BR112018075653A2 (pt) | 2016-06-08 | 2019-08-27 | Abbvie Inc | anticorpos anti-b7-h3 e conjugados anticorpo fármaco |
CN116284404A (zh) | 2016-06-08 | 2023-06-23 | 艾伯维公司 | 抗b7-h3抗体和抗体药物偶联物 |
RU2680834C1 (ru) * | 2018-05-23 | 2019-02-28 | федеральное государственное автономное образовательное учреждение высшего образования "Казанский (Приволжский) федеральный университет" (ФГАОУ ВО КФУ) | Противоопухолевая композиция доксорубицина с ингибитором АТФ-зависимых обратных транспортеров клеток |
AR124681A1 (es) | 2021-01-20 | 2023-04-26 | Abbvie Inc | Conjugados anticuerpo-fármaco anti-egfr |
Family Cites Families (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4206221A (en) * | 1979-01-03 | 1980-06-03 | The United States Of America As Represented By The Secretary Of Agriculture | Cephalomannine and its use in treating leukemic tumors |
FR2601676B1 (fr) | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Procede de preparation du taxol et du desacetyl-10 taxol |
FR2601675B1 (fr) * | 1986-07-17 | 1988-09-23 | Rhone Poulenc Sante | Derives du taxol, leur preparation et les compositions pharmaceutiques qui les contiennent |
US4876399A (en) * | 1987-11-02 | 1989-10-24 | Research Corporation Technologies, Inc. | Taxols, their preparation and intermediates thereof |
FR2623089B1 (fr) * | 1987-11-13 | 1990-04-27 | Pf Medicament | Composition pharmaceutique pour l'administration parenterale de navelbine |
GB8806224D0 (en) | 1988-03-16 | 1988-04-13 | Johnson Matthey Plc | Platinum chemotherapeutic product |
US5136060A (en) * | 1989-11-14 | 1992-08-04 | Florida State University | Method for preparation of taxol using an oxazinone |
US5015744A (en) * | 1989-11-14 | 1991-05-14 | Florida State University | Method for preparation of taxol using an oxazinone |
MX9102128A (es) | 1990-11-23 | 1992-07-08 | Rhone Poulenc Rorer Sa | Derivados de taxano,procedimiento para su preparacion y composicion farmaceutica que los contiene |
US5399363A (en) * | 1991-01-25 | 1995-03-21 | Eastman Kodak Company | Surface modified anticancer nanoparticles |
US5645988A (en) | 1991-05-08 | 1997-07-08 | The United States Of America As Represented By The Department Of Health And Human Services | Methods of identifying drugs with selective effects against cancer cells |
AU2005692A (en) * | 1991-05-08 | 1992-12-21 | United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Method for designing cancer treatment regimens and methods and pharmaceutical compositions for the treatment of cancer |
US5284864A (en) * | 1991-09-23 | 1994-02-08 | Florida State University | Butenyl substituted taxanes and pharmaceutical compositions containing them |
US5229526A (en) * | 1991-09-23 | 1993-07-20 | Florida State University | Metal alkoxides |
US5262409A (en) * | 1991-10-11 | 1993-11-16 | Fred Hutchinson Cancer Research Center | Binary tumor therapy |
US5294737A (en) * | 1992-02-27 | 1994-03-15 | The Research Foundation State University Of New York | Process for the production of chiral hydroxy-β-lactams and hydroxyamino acids derived therefrom |
US5294637A (en) * | 1992-07-01 | 1994-03-15 | Bristol-Myers Squibb Company | Fluoro taxols |
US5254580A (en) * | 1993-01-19 | 1993-10-19 | Bristol-Myers Squibb Company | 7,8-cyclopropataxanes |
US5495501A (en) * | 1992-09-02 | 1996-02-27 | Fujitsu Limited | Communication system including a digital roll-off filter |
FR2697752B1 (fr) | 1992-11-10 | 1995-04-14 | Rhone Poulenc Rorer Sa | Compositions antitumorales contenant des dérivés du taxane. |
FR2698871B1 (fr) * | 1992-12-09 | 1995-02-24 | Rhone Poulenc Rorer Sa | Nouveau taxoïdes, leur préparation et les compositions pharmaceutiques qui les contiennent. |
US5814658A (en) * | 1992-12-09 | 1998-09-29 | Rhone-Poulenc Rorer S.A. | Taxoids, their preparation and pharmaceutical compositions containing them |
IL107950A (en) | 1992-12-15 | 2001-04-30 | Upjohn Co | b 7, b 8 - Matano - Taxols, their preparation and pharmaceutical preparations against malignant tumors containing them |
US6441026B1 (en) * | 1993-11-08 | 2002-08-27 | Aventis Pharma S.A. | Antitumor compositions containing taxane derivatives |
WO1995015303A1 (en) | 1993-12-03 | 1995-06-08 | Exxon Research And Engineering Company | Carbonyl containing compounds |
US6214388B1 (en) | 1994-11-09 | 2001-04-10 | The Regents Of The University Of California | Immunoliposomes that optimize internalization into target cells |
ZA9811162B (en) | 1997-12-12 | 2000-06-07 | Genentech Inc | Treatment with anti-ERBB2 antibodies. |
EP0982028A1 (en) | 1998-08-20 | 2000-03-01 | Aventis Pharma S.A. | New use of taxoid derivatives |
DE60031268T2 (de) * | 1999-04-14 | 2007-05-24 | Dana-Farber Cancer Institute, Inc., Boston | Verfahren und zusammansetzung zur behandlung von krebs |
US6465448B1 (en) * | 1999-08-13 | 2002-10-15 | Case Western Reserve University | Methoxyamine potentiation of temozolomide anti-cancer activity |
US6448030B1 (en) * | 2000-02-18 | 2002-09-10 | University Of Nevada-Las Vegas | Method for predicting the efficacy of anti-cancer drugs |
US7696923B2 (en) * | 2005-02-03 | 2010-04-13 | Mexens Intellectual Property Holding Llc | System and method for determining geographic location of wireless computing devices |
-
1992
- 1992-11-10 FR FR9213525A patent/FR2697752B1/fr not_active Expired - Lifetime
-
1993
- 1993-11-02 ZA ZA938182A patent/ZA938182B/xx unknown
- 1993-11-05 MX MX9306924A patent/MX9306924A/es not_active IP Right Cessation
- 1993-11-06 TW TW082109299A patent/TW386877B/zh not_active IP Right Cessation
- 1993-11-08 EP EP93924682A patent/EP0667771B1/fr not_active Expired - Lifetime
- 1993-11-08 AT AT97117252T patent/ATE205083T1/de active
- 1993-11-08 NZ NZ257585A patent/NZ257585A/en not_active IP Right Cessation
- 1993-11-08 DK DK97117252T patent/DK0827745T3/da active
- 1993-11-08 KR KR1019950701848A patent/KR100334051B1/ko not_active IP Right Cessation
- 1993-11-08 DK DK93924682T patent/DK0667771T3/da active
- 1993-11-08 US US08/424,470 patent/US5728687A/en not_active Expired - Lifetime
- 1993-11-08 ES ES97117252T patent/ES2163076T3/es not_active Expired - Lifetime
- 1993-11-08 PL PL93308902A patent/PL173951B1/pl unknown
- 1993-11-08 EP EP01101665A patent/EP1093811A1/fr not_active Ceased
- 1993-11-08 RU RU95112842A patent/RU2131250C1/ru active
- 1993-11-08 PT PT97117252T patent/PT827745E/pt unknown
- 1993-11-08 DE DE69318033T patent/DE69318033T2/de not_active Expired - Lifetime
- 1993-11-08 CA CA002149055A patent/CA2149055C/fr not_active Expired - Lifetime
- 1993-11-08 AU AU54253/94A patent/AU680845B2/en not_active Expired
- 1993-11-08 EP EP02028931A patent/EP1295597A1/fr not_active Withdrawn
- 1993-11-08 SK SK595-95A patent/SK282867B6/sk not_active IP Right Cessation
- 1993-11-08 EP EP97117252A patent/EP0827745B1/fr not_active Expired - Lifetime
- 1993-11-08 ES ES93924682T patent/ES2114620T3/es not_active Expired - Lifetime
- 1993-11-08 CZ CZ19951193A patent/CZ288033B6/cs not_active IP Right Cessation
- 1993-11-08 WO PCT/FR1993/001096 patent/WO1994010995A1/fr active IP Right Grant
- 1993-11-08 DE DE69330724T patent/DE69330724T2/de not_active Expired - Lifetime
- 1993-11-08 HU HU9501372A patent/HU223773B1/hu active IP Right Grant
- 1993-11-08 AT AT93924682T patent/ATE165002T1/de active
- 1993-11-08 KR KR1020017011197A patent/KR20030096445A/ko active Search and Examination
- 1993-11-08 JP JP51178394A patent/JP3974938B2/ja not_active Expired - Lifetime
-
1995
- 1995-04-05 NO NO19951327A patent/NO315027B1/no not_active IP Right Cessation
- 1995-05-09 FI FI952248A patent/FI952248A0/fi not_active Application Discontinuation
-
1997
- 1997-11-10 US US08/967,036 patent/US5908835A/en not_active Expired - Lifetime
-
1998
- 1998-04-16 GR GR970403093T patent/GR3026666T3/el unknown
-
1999
- 1999-08-10 US US09/371,520 patent/US6214863B1/en not_active Expired - Lifetime
-
2000
- 2000-02-18 US US09/506,902 patent/US6239167B1/en not_active Expired - Lifetime
- 2000-11-08 CZ CZ20004149A patent/CZ290120B6/cs not_active IP Right Cessation
-
2001
- 2001-09-06 GR GR20010400691T patent/GR3036537T3/el unknown
-
2002
- 2002-04-30 US US10/134,391 patent/US20020197245A1/en not_active Abandoned
-
2003
- 2003-04-25 US US10/422,823 patent/US7989489B2/en not_active Expired - Fee Related
- 2003-12-30 US US10/747,372 patent/US8124650B2/en not_active Expired - Fee Related
- 2003-12-30 US US10/747,279 patent/US8101652B2/en not_active Expired - Fee Related
- 2003-12-30 US US10/747,410 patent/US20040152673A1/en not_active Abandoned
- 2003-12-30 US US10/747,206 patent/US7994212B2/en not_active Expired - Fee Related
- 2003-12-30 US US10/747,207 patent/US20040157786A1/en not_active Abandoned
-
2005
- 2005-06-10 US US11/149,178 patent/US20050226940A1/en not_active Abandoned
-
2011
- 2011-06-30 US US13/173,268 patent/US20110263522A1/en not_active Abandoned
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO315027B1 (no) | Antitumor-preparater inneholdende taxan-derivater | |
CA2440160C (en) | Antitumor compositions containing taxane derivatives | |
AU2002244877A1 (en) | Antitumor compositions containing taxane derivatives | |
NO332661B1 (no) | Farmasoytisk kombinasjon omfattende combretastatin og anticancerforbindelser | |
MX2008014404A (es) | Tratamientos anticancer con combinacion de docetaxel y ecteinascidin. | |
US6939893B2 (en) | Method of reducing toxicity of anticancer agents | |
WESSELS et al. | IN VIVO POTENTIATION OF c/s-DIAMMINEDICHLOROPLATINUM (II) ANTITUMOR ACTIVITY BY PRETREATMENT WITH SPARSOMYCIN | |
MXPA99008020A (en) | Compositions for treating tumors containing shark cartilage extracts and anti-neoplastic agents |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MK1K | Patent expired |