PL198185B1 - Zastosowanie Ekteinascydyny 743 do wytwarzania kompozycji farmaceutycznej - Google Patents
Zastosowanie Ekteinascydyny 743 do wytwarzania kompozycji farmaceutycznejInfo
- Publication number
- PL198185B1 PL198185B1 PL352931A PL35293100A PL198185B1 PL 198185 B1 PL198185 B1 PL 198185B1 PL 352931 A PL352931 A PL 352931A PL 35293100 A PL35293100 A PL 35293100A PL 198185 B1 PL198185 B1 PL 198185B1
- Authority
- PL
- Poland
- Prior art keywords
- cancer
- sarcoma
- hours
- administration
- dose
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 38
- 201000011510 cancer Diseases 0.000 title claims abstract description 37
- 239000000203 mixture Substances 0.000 title claims description 17
- PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 claims abstract description 46
- 238000011282 treatment Methods 0.000 claims abstract description 29
- 239000003814 drug Substances 0.000 claims abstract description 16
- 238000001802 infusion Methods 0.000 claims description 40
- 229960000977 trabectedin Drugs 0.000 claims description 31
- XXPXYPLPSDPERN-UHFFFAOYSA-N Ecteinascidin 743 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(O)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C XXPXYPLPSDPERN-UHFFFAOYSA-N 0.000 claims description 30
- 238000001990 intravenous administration Methods 0.000 claims description 22
- 206010039491 Sarcoma Diseases 0.000 claims description 19
- 206010006187 Breast cancer Diseases 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 11
- 208000026310 Breast neoplasm Diseases 0.000 claims description 10
- 238000002512 chemotherapy Methods 0.000 claims description 10
- 238000009472 formulation Methods 0.000 claims description 10
- 206010006007 bone sarcoma Diseases 0.000 claims description 6
- 201000001441 melanoma Diseases 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 206010027406 Mesothelioma Diseases 0.000 claims description 5
- 206010033128 Ovarian cancer Diseases 0.000 claims description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 5
- 206010055008 Gastric sarcoma Diseases 0.000 claims description 4
- 208000005927 Myosarcoma Diseases 0.000 claims description 4
- 230000006872 improvement Effects 0.000 claims description 4
- 201000002077 muscle cancer Diseases 0.000 claims description 4
- 201000002575 ocular melanoma Diseases 0.000 claims description 4
- 206010027476 Metastases Diseases 0.000 claims description 3
- 201000002660 colon sarcoma Diseases 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 13
- 230000004044 response Effects 0.000 description 10
- 230000001988 toxicity Effects 0.000 description 10
- 231100000419 toxicity Toxicity 0.000 description 10
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 9
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241000798369 Ecteinascidia turbinata Species 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 229940045799 anthracyclines and related substance Drugs 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 102000003929 Transaminases Human genes 0.000 description 4
- 108090000340 Transaminases Proteins 0.000 description 4
- 210000000988 bone and bone Anatomy 0.000 description 4
- 231100000371 dose-limiting toxicity Toxicity 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 206010061289 metastatic neoplasm Diseases 0.000 description 4
- 238000006257 total synthesis reaction Methods 0.000 description 4
- 206010025323 Lymphomas Diseases 0.000 description 3
- 229940123237 Taxane Drugs 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- 230000001093 anti-cancer Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001394 metastastic effect Effects 0.000 description 3
- 208000037819 metastatic cancer Diseases 0.000 description 3
- 208000011575 metastatic malignant neoplasm Diseases 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 206010065553 Bone marrow failure Diseases 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 241000798368 Ecteinascidia Species 0.000 description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 description 2
- 208000001382 Experimental Melanoma Diseases 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LMKHFHFSEWJQID-UHFFFAOYSA-N Saframycin B Natural products COC1=C(C)C(=O)C2=C(CC3C4N(C)C(CN3C2CNC(=O)C(=O)C)CC5=C4C(=O)C(=C(C)C5=O)OC)C1=O LMKHFHFSEWJQID-UHFFFAOYSA-N 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 206010003549 asthenia Diseases 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 231100000026 common toxicity Toxicity 0.000 description 2
- 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 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000003978 infusion fluid Substances 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 208000004235 neutropenia Diseases 0.000 description 2
- 208000011932 ovarian sarcoma Diseases 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 208000037821 progressive disease Diseases 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 206010043554 thrombocytopenia Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 210000001944 turbinate Anatomy 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 206010051779 Bone marrow toxicity Diseases 0.000 description 1
- 206010055113 Breast cancer metastatic Diseases 0.000 description 1
- OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 206010024612 Lipoma Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 229930190585 Saframycin Natural products 0.000 description 1
- 101100537665 Trypanosoma cruzi TOR gene Proteins 0.000 description 1
- 241000251555 Tunicata Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 231100000366 bone marrow toxicity Toxicity 0.000 description 1
- 201000007455 central nervous system cancer Diseases 0.000 description 1
- 208000025997 central nervous system neoplasm Diseases 0.000 description 1
- 201000008208 central nervous system sarcoma Diseases 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 201000010387 gastric liposarcoma Diseases 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 206010024627 liposarcoma Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 201000010893 malignant breast melanoma Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 210000003716 mesoderm Anatomy 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- JNEGMBHBUAJRSX-SHUHUVMISA-N saframycin a Chemical compound C([C@H](N1C)[C@@H]2C#N)C(C(C(C)=C(OC)C3=O)=O)=C3[C@@H]1[C@H](C1)N2[C@@H](CNC(=O)C(C)=O)C2=C1C(=O)C(C)=C(OC)C2=O JNEGMBHBUAJRSX-SHUHUVMISA-N 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 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 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical class C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 208000007631 thrombocytopenia 4 Diseases 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- MEYZYGMYMLNUHJ-UHFFFAOYSA-N tunicamycin Natural products CC(C)CCCCCCCCCC=CC(=O)NC1C(O)C(O)C(CC(O)C2OC(C(O)C2O)N3C=CC(=O)NC3=O)OC1OC4OC(CO)C(O)C(O)C4NC(=O)C MEYZYGMYMLNUHJ-UHFFFAOYSA-N 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
-
- 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
- A61K31/4995—Pyrazines or piperazines forming part of bridged ring systems
-
- 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
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9911183.3A GB9911183D0 (en) | 1999-05-13 | 1999-05-13 | Treatment of cancers |
| GBGB9911346.6A GB9911346D0 (en) | 1999-05-14 | 1999-05-14 | Treatment of cancers |
| GBGB9918534.0A GB9918534D0 (en) | 1999-08-05 | 1999-08-05 | Treatment of cancers |
| GBGB9927005.0A GB9927005D0 (en) | 1999-11-15 | 1999-11-15 | Treatment of cancers |
| GBGB9927106.6A GB9927106D0 (en) | 1999-11-16 | 1999-11-16 | Cancer treatment |
| GB0007637A GB0007637D0 (en) | 2000-03-29 | 2000-03-29 | Antitumour compound |
| PCT/GB2000/001857 WO2000069441A1 (en) | 1999-05-13 | 2000-05-15 | Compositions and uses of et743 for treating cancer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL352931A1 PL352931A1 (en) | 2003-09-22 |
| PL198185B1 true PL198185B1 (pl) | 2008-06-30 |
Family
ID=27546594
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL352931A PL198185B1 (pl) | 1999-05-13 | 2000-05-15 | Zastosowanie Ekteinascydyny 743 do wytwarzania kompozycji farmaceutycznej |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US8119638B2 (enExample) |
| EP (3) | EP1716853B9 (enExample) |
| JP (2) | JP2002544231A (enExample) |
| KR (1) | KR20020019914A (enExample) |
| CN (2) | CN1360503A (enExample) |
| AR (1) | AR028476A1 (enExample) |
| AT (3) | ATE500830T1 (enExample) |
| AU (2) | AU777417B2 (enExample) |
| BG (1) | BG65680B1 (enExample) |
| BR (1) | BR0010531A (enExample) |
| CA (1) | CA2373794C (enExample) |
| CY (4) | CY1105818T1 (enExample) |
| CZ (1) | CZ301482B6 (enExample) |
| DE (4) | DE122008000013I1 (enExample) |
| DK (3) | DK1176964T3 (enExample) |
| ES (2) | ES2272279T3 (enExample) |
| FR (1) | FR08C0013I2 (enExample) |
| HU (2) | HU229866B1 (enExample) |
| IL (2) | IL146434A0 (enExample) |
| LU (1) | LU91418I2 (enExample) |
| MX (1) | MXPA01011562A (enExample) |
| MY (1) | MY164077A (enExample) |
| NL (1) | NL300337I2 (enExample) |
| NO (2) | NO324564B1 (enExample) |
| NZ (1) | NZ515423A (enExample) |
| PL (1) | PL198185B1 (enExample) |
| PT (3) | PT1176964E (enExample) |
| SI (3) | SI1176964T1 (enExample) |
| SK (1) | SK287580B6 (enExample) |
| TR (1) | TR200103819T2 (enExample) |
| UA (1) | UA74782C2 (enExample) |
| WO (1) | WO2000069441A1 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MY164077A (en) | 1999-05-13 | 2017-11-30 | Pharma Mar Sa | Compositions and uses of et743 for treating cancer |
| MXPA02011319A (es) | 2000-05-15 | 2003-06-06 | Pharma Mar Sa | Analogos antitumorales de ecteinascidina 743. |
| EA005564B1 (ru) * | 2000-11-06 | 2005-04-28 | Π€Π°ΡΠΌΠ° ΠΠ°Ρ, Π‘.Π. | ΠΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠ΅ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΡΠ΅ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠ΅ ΡΡΠ΅Π΄ΡΡΠ²Π° |
| GB0117402D0 (en) * | 2001-07-17 | 2001-09-05 | Pharma Mar Sa | New antitumoral derivatives of et-743 |
| KR20050038578A (ko) * | 2001-10-19 | 2005-04-27 | νλ₯΄λ§ λ§λ₯΄, μμ€.μμ΄. | νμ’ μμ± νν©λ¬Όμ μμΉλ£μ μμ΄μμ ν₯μλ μ©λ |
| GB0202544D0 (en) | 2002-02-04 | 2002-03-20 | Pharma Mar Sa | The synthesis of naturally occuring ecteinascidins and related compounds |
| 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 |
| SI1689404T1 (sl) * | 2003-11-13 | 2009-02-28 | Pharma Mar Sau | Kombinacija et-743 s 5-fluorouracil pro zdravili za zdravljenje raka |
| CN1897949A (zh) * | 2003-11-14 | 2007-01-17 | 马ε°θ―εε ¬εΈ | ε ε«δ½Ώη¨etοΌ743εη΄«ζιζ₯ζ²»ηηηηθεηζ³ |
| GB0326486D0 (en) * | 2003-11-14 | 2003-12-17 | Pharma Mar Sau | Combination treatment |
| AU2005261860A1 (en) * | 2004-07-09 | 2006-01-19 | Pharma Mar, S.A. | Use of ecteinascidin in the treatment of cancer in patients with low level of BRCA1 |
| RU2359700C2 (ru) * | 2004-10-26 | 2009-06-27 | Π€Π°ΡΠΌΠ° ΠΠ°Ρ Π‘.Π., Π‘ΠΎΡΡΠ΅Π΄Π°Π΄ Π£Π½ΠΈΠΏΠ΅ΡΡΠΎΠ½Π°Π»Ρ | ΠΠ΅Π³ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ Π»ΠΈΠΏΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΡΠΉ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½ Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΡΠΊΡΠ΅ΠΈΠ½Π°ΡΡΠΈΠ΄ΠΈΠ½ΠΎΠΌ 743 (ecteinescidin 743) |
| KR101188691B1 (ko) * | 2004-10-29 | 2012-10-09 | νλ₯΄λ§ λ§λ₯΄ μμ€.μμ΄. | μν°λμλ λ° λμ¬μΉ΄λΌμ΄λλ₯Ό ν¬ν¨νλ μ μ |
| GB0522082D0 (en) * | 2005-10-31 | 2005-12-07 | Pharma Mar Sa | Formulations |
| MX2008014404A (es) * | 2006-05-12 | 2008-11-27 | Pharma Mar Sa | Tratamientos anticancer con combinacion de docetaxel y ecteinascidin. |
| CA2703026A1 (en) * | 2007-10-19 | 2009-04-23 | Rafael Rosell Costa | Prognostic molecular markers for et-743 treatment |
| AU2017215603A1 (en) * | 2016-02-04 | 2018-08-09 | Jiangsu Hengrui Medicine Co., Ltd. | Trabectedin-inclusive injectable pharmaceutical composition for gastrointestinal external use and method for manufacturing the same |
| US11332480B2 (en) | 2017-04-27 | 2022-05-17 | Pharma Mar, S.A. | Antitumoral compounds |
| WO2020239478A1 (en) | 2019-05-28 | 2020-12-03 | Pharma Mar, S.A. | Trabectedin for treating sarcomas based on genomic markers |
| CN112574234B (zh) * | 2019-09-27 | 2022-05-24 | ζ±θζηε»θ―θ‘δ»½ζιε ¬εΈ | δΈη§ζ΅·ιη΄ θ‘ηη©ηεΆε€ζΉζ³ |
| BR112022020812A2 (pt) | 2020-04-15 | 2022-11-29 | Ever Valinject Gmbh | Composição farmacΓͺutica compreendendo trabectedina e um aminoacido, formulação liofilizada e uma solução de injeção intravenosa compreendendo dita composição |
| EP3960177A1 (en) * | 2020-08-26 | 2022-03-02 | Anturec Pharmaceuticals GmbH | Composition comprising ttf-ngr for use in treating soft-tissue sarcoma |
| AU2022277799A1 (en) * | 2021-05-19 | 2023-12-21 | Pharma Mar, S.A. | Dosage regimens for ecubectedin |
| US12303506B2 (en) | 2022-01-20 | 2025-05-20 | Extrovis Ag | Trabectedin composition |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5089273A (en) | 1986-06-09 | 1992-02-18 | Board Of Trustees Of The University Of Illinois | Ecteinascidins 729, 743, 745, 759A, 759B and 770 |
| US5149804A (en) * | 1990-11-30 | 1992-09-22 | The Board Of Trustees Of The University Of Illinois | Ecteinascidins 736 and 722 |
| US5256663A (en) * | 1986-06-09 | 1993-10-26 | The Board Of Trustees Of The University Of Illinois | Compositions comprising ecteinascidins and a method of treating herpes simplex virus infections therewith |
| AU589282B2 (en) * | 1986-06-09 | 1989-10-05 | University Of Illinois | Ecteinascidins 729, 743, 745, 759a, 759b and 770 |
| DE3635711A1 (de) | 1986-10-21 | 1988-04-28 | Knoll Ag | 5-nitrobenzo(de)isochinolin-1,3-dione, ihre herstellung und verwendung |
| GB8805268D0 (en) * | 1988-03-04 | 1988-04-07 | Glaxo Group Ltd | Medicaments |
| GB9101221D0 (en) * | 1991-01-19 | 1991-02-27 | Smithkline Beecham Plc | Pharmaceuticals |
| US5721352A (en) | 1991-02-19 | 1998-02-24 | University Of Florida Research Foundation | Entomopoxvirus expression system |
| FR2697752B1 (fr) | 1992-11-10 | 1995-04-14 | Rhone Poulenc Rorer Sa | Compositions antitumorales contenant des dΓ©rivΓ©s du taxane. |
| US5891704A (en) * | 1992-11-19 | 1999-04-06 | Anticancer, Inc. | Method to produce high levels of methioninase |
| WO1994026250A1 (en) * | 1993-05-14 | 1994-11-24 | Depotech Corporation | Method for treating neurological disorders |
| US5478932A (en) * | 1993-12-02 | 1995-12-26 | The Board Of Trustees Of The University Of Illinois | Ecteinascidins |
| US20040059112A1 (en) | 1994-02-18 | 2004-03-25 | Rinehart Kenneth L. | Ecteinascidins |
| US5919816A (en) * | 1994-11-14 | 1999-07-06 | Bionumerik Pharmaceuticals, Inc. | Formulations and methods of reducing toxicity of antineoplastic agents |
| GB9508195D0 (en) | 1995-04-20 | 1995-06-07 | Univ British Columbia | Novel biologically active compounds and compositions,their use and derivation |
| US5721362A (en) * | 1996-09-18 | 1998-02-24 | President And Fellows Of Harvard College | Process for producing ecteinascidin compounds |
| DE69734290T2 (de) * | 1996-11-05 | 2006-07-06 | The Children's Medical Center Corp., Boston | Mittel zur hemmung von angiogenese enthaltend thalodomid und einen nsaid |
| IL123740A0 (en) * | 1997-03-28 | 1998-10-30 | Pfizer | NK-1 receptor antagonists for the treatment of delayed emesis |
| US5985876A (en) | 1997-04-15 | 1999-11-16 | Univ Illinois | Nucleophile substituted ecteinascidins and N-oxide ecteinascidins |
| DE19720312A1 (de) * | 1997-05-15 | 1998-11-19 | Hoechst Ag | Zubereitung mit erhΓΆhter in vivo VertrΓ€glichkeit |
| GB9801231D0 (en) * | 1997-06-05 | 1998-03-18 | Merck & Co Inc | A method of treating cancer |
| CZ301083B6 (cs) | 1998-04-06 | 2009-11-04 | The Board Of Trustees Of The University Of Illinois | EkteinascidinovΓ‘ sloucenina, farmaceutickΓ½ prostredek ji obsahujΓcΓ a jejΓ pouΕΎitΓ |
| KR100643092B1 (ko) * | 1998-05-11 | 2006-11-10 | νλ₯΄λ§ λ§λ₯΄, μμ€.μμ΄. | μν μΈμμλ 743μ λμ¬μ°λ¬Ό |
| US6124292A (en) | 1998-09-30 | 2000-09-26 | President And Fellows Of Harvard College | Synthetic analogs of ecteinascidin-743 |
| MY164077A (en) | 1999-05-13 | 2017-11-30 | Pharma Mar Sa | Compositions and uses of et743 for treating cancer |
| AR035842A1 (es) | 1999-05-14 | 2004-07-21 | Pharma Mar Sa | Metodo de hemisintesis para la formacion de compuestos intermediarios y derivados y de estructuras relacionadas con la ecteinascidina y de tetrahidroisoquinolinfenoles y compuestos intermediarios de aplicacion en dicho metodo |
| JP5219323B2 (ja) | 2000-04-12 | 2013-06-26 | γγ‘γ«γγ»γγΌγ«γ»γ½γ·γ¨γγΌγγ»γ’γγγ | ζθ «ηζ§γ¨γ―γγγ΅γ€γΈγ³θͺε°δ½ |
| US7247892B2 (en) | 2000-04-24 | 2007-07-24 | Taylor Geoff W | Imaging array utilizing thyristor-based pixel elements |
| MXPA02011319A (es) | 2000-05-15 | 2003-06-06 | Pharma Mar Sa | Analogos antitumorales de ecteinascidina 743. |
| US7420051B2 (en) | 2000-05-15 | 2008-09-02 | Pharma Mar, S.A. | Synthetic process for the manufacture of an ecteinaschidin compound |
| US20020137663A1 (en) | 2000-08-11 | 2002-09-26 | Forman Barry M. | The anti-neoplastic agent ET-743 inhibits trans activation by SXR |
| EA005564B1 (ru) | 2000-11-06 | 2005-04-28 | Π€Π°ΡΠΌΠ° ΠΠ°Ρ, Π‘.Π. | ΠΡΡΠ΅ΠΊΡΠΈΠ²Π½ΡΠ΅ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΡΠ΅ Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΠ΅ ΡΡΠ΅Π΄ΡΡΠ²Π° |
| EP1360337A1 (en) | 2001-02-09 | 2003-11-12 | The Regents Of The University Of California | Ecteinascidin family compounds: compositions and methods |
| US20030027799A1 (en) | 2001-03-30 | 2003-02-06 | Shire Biochem Inc. | Methods of treating cancer using a combination of drugs |
| GB0121285D0 (en) | 2001-09-03 | 2001-10-24 | Cancer Res Ventures Ltd | Anti-cancer combinations |
| KR20050038578A (ko) | 2001-10-19 | 2005-04-27 | νλ₯΄λ§ λ§λ₯΄, μμ€.μμ΄. | νμ’ μμ± νν©λ¬Όμ μμΉλ£μ μμ΄μμ ν₯μλ μ©λ |
| US20040019027A1 (en) | 2002-04-12 | 2004-01-29 | Barry Forman | Method of treating cerebrotendinous xanthomatosis |
| 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 |
| SI1689404T1 (sl) | 2003-11-13 | 2009-02-28 | Pharma Mar Sau | Kombinacija et-743 s 5-fluorouracil pro zdravili za zdravljenje raka |
| GB0326486D0 (en) | 2003-11-14 | 2003-12-17 | Pharma Mar Sau | Combination treatment |
| CN1897949A (zh) | 2003-11-14 | 2007-01-17 | 马ε°θ―εε ¬εΈ | ε ε«δ½Ώη¨etοΌ743εη΄«ζιζ₯ζ²»ηηηηθεηζ³ |
| AU2005261860A1 (en) | 2004-07-09 | 2006-01-19 | Pharma Mar, S.A. | Use of ecteinascidin in the treatment of cancer in patients with low level of BRCA1 |
| AU2005288696A1 (en) | 2004-09-28 | 2006-04-06 | Pharma Mar S.A., Sociedad Unipersonal | Ecteinascidin compounds as anti -inflammatory agents |
| RU2359700C2 (ru) | 2004-10-26 | 2009-06-27 | Π€Π°ΡΠΌΠ° ΠΠ°Ρ Π‘.Π., Π‘ΠΎΡΡΠ΅Π΄Π°Π΄ Π£Π½ΠΈΠΏΠ΅ΡΡΠΎΠ½Π°Π»Ρ | ΠΠ΅Π³ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΉ Π»ΠΈΠΏΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΡΠΉ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½ Π² ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ Ρ ΡΠΊΡΠ΅ΠΈΠ½Π°ΡΡΠΈΠ΄ΠΈΠ½ΠΎΠΌ 743 (ecteinescidin 743) |
| KR101188691B1 (ko) | 2004-10-29 | 2012-10-09 | νλ₯΄λ§ λ§λ₯΄ μμ€.μμ΄. | μν°λμλ λ° λμ¬μΉ΄λΌμ΄λλ₯Ό ν¬ν¨νλ μ μ |
| DE602006020335D1 (de) | 2005-11-25 | 2011-04-07 | Pharma Mar Sa | Verwendung von parp-1-hemmern |
| MX2008014404A (es) | 2006-05-12 | 2008-11-27 | Pharma Mar Sa | Tratamientos anticancer con combinacion de docetaxel y ecteinascidin. |
-
2000
- 2000-05-13 MY MYPI20002107A patent/MY164077A/en unknown
- 2000-05-15 AR ARP000102321A patent/AR028476A1/es not_active Application Discontinuation
- 2000-05-15 DE DE122008000013C patent/DE122008000013I1/de active Pending
- 2000-05-15 CA CA002373794A patent/CA2373794C/en not_active Expired - Lifetime
- 2000-05-15 IL IL14643400A patent/IL146434A0/xx active IP Right Grant
- 2000-05-15 JP JP2000617900A patent/JP2002544231A/ja not_active Withdrawn
- 2000-05-15 EP EP06014005A patent/EP1716853B9/en not_active Expired - Lifetime
- 2000-05-15 DE DE60030554T patent/DE60030554T8/de active Active
- 2000-05-15 AU AU45975/00A patent/AU777417B2/en not_active Expired
- 2000-05-15 CN CN00809976A patent/CN1360503A/zh active Pending
- 2000-05-15 PT PT00927584T patent/PT1176964E/pt unknown
- 2000-05-15 SK SK1644-2001A patent/SK287580B6/sk not_active IP Right Cessation
- 2000-05-15 MX MXPA01011562A patent/MXPA01011562A/es active IP Right Grant
- 2000-05-15 EP EP06011784A patent/EP1702618B1/en not_active Expired - Lifetime
- 2000-05-15 CZ CZ20014081A patent/CZ301482B6/cs not_active IP Right Cessation
- 2000-05-15 DK DK00927584T patent/DK1176964T3/da active
- 2000-05-15 DE DE60045720T patent/DE60045720D1/de not_active Expired - Lifetime
- 2000-05-15 EP EP00927584A patent/EP1176964B8/en not_active Expired - Lifetime
- 2000-05-15 DK DK06011784T patent/DK1702618T3/da active
- 2000-05-15 KR KR1020017014479A patent/KR20020019914A/ko not_active Ceased
- 2000-05-15 ES ES00927584T patent/ES2272279T3/es not_active Expired - Lifetime
- 2000-05-15 PL PL352931A patent/PL198185B1/pl unknown
- 2000-05-15 CN CNB2005100091622A patent/CN100477993C/zh not_active Expired - Lifetime
- 2000-05-15 TR TR2001/03819T patent/TR200103819T2/xx unknown
- 2000-05-15 SI SI200030905T patent/SI1176964T1/sl unknown
- 2000-05-15 NZ NZ515423A patent/NZ515423A/en not_active IP Right Cessation
- 2000-05-15 PT PT06011784T patent/PT1702618E/pt unknown
- 2000-05-15 SI SI200030977T patent/SI1702618T1/sl unknown
- 2000-05-15 AT AT06014005T patent/ATE500830T1/de active
- 2000-05-15 AT AT00927584T patent/ATE338552T1/de active
- 2000-05-15 AT AT06011784T patent/ATE375795T1/de active
- 2000-05-15 BR BR0010531-7A patent/BR0010531A/pt not_active Application Discontinuation
- 2000-05-15 DK DK06014005.0T patent/DK1716853T3/da active
- 2000-05-15 HU HU0201187A patent/HU229866B1/hu active Protection Beyond IP Right Term
- 2000-05-15 UA UA2001128559A patent/UA74782C2/uk unknown
- 2000-05-15 WO PCT/GB2000/001857 patent/WO2000069441A1/en not_active Ceased
- 2000-05-15 DE DE60036826T patent/DE60036826T2/de not_active Expired - Lifetime
- 2000-05-15 ES ES06011784T patent/ES2294756T3/es not_active Expired - Lifetime
- 2000-05-15 PT PT06014005T patent/PT1716853E/pt unknown
- 2000-05-15 SI SI200031067T patent/SI1716853T1/sl unknown
-
2001
- 2001-11-11 IL IL146434A patent/IL146434A/en active Protection Beyond IP Right Term
- 2001-11-12 NO NO20015516A patent/NO324564B1/no not_active IP Right Cessation
- 2001-12-03 BG BG106171A patent/BG65680B1/bg unknown
-
2005
- 2005-01-14 AU AU2005200180A patent/AU2005200180B9/en not_active Expired
-
2006
- 2006-11-30 CY CY20061101734T patent/CY1105818T1/el unknown
-
2007
- 2007-06-28 US US11/769,873 patent/US8119638B2/en not_active Expired - Fee Related
-
2008
- 2008-01-16 CY CY20081100059T patent/CY1107143T1/el unknown
- 2008-02-22 NL NL300337C patent/NL300337I2/nl unknown
- 2008-03-10 LU LU91418C patent/LU91418I2/fr unknown
- 2008-04-07 CY CY200800007C patent/CY2008007I1/el unknown
- 2008-04-16 FR FR08C0013C patent/FR08C0013I2/fr active Active
- 2008-05-16 NO NO2008005C patent/NO2008005I1/no not_active IP Right Cessation
-
2011
- 2011-06-08 CY CY20111100545T patent/CY1112753T1/el unknown
-
2012
- 2012-05-02 JP JP2012105249A patent/JP5777562B2/ja not_active Expired - Lifetime
-
2015
- 2015-01-06 HU HUS1500001C patent/HUS1500001I1/hu unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8119638B2 (en) | Compositions and uses of ET743 for treating cancer | |
| RU2306933C2 (ru) | Π£Π»ΡΡΡΠ΅Π½Π½Π°Ρ ΡΡ Π΅ΠΌΠ° ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ Π² ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΡΠ°ΠΊΠ° | |
| AU2002343548A1 (en) | Improved use of antitumoral compound in cancer therapy | |
| EP1689404B1 (en) | Combination of et-743 with 5-fluorouracil pro-drugs for the treatment of cancer | |
| WO2005049030A1 (en) | Combination therapy comprising the use of et-743 and paclitaxel for treating cancer | |
| RU2266734C2 (ru) | ΠΠΎΠΌΠΏΠΎΠ·ΠΈΡΠΈΠΈ ΠΈ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π΅Ρ743 Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ ΠΎΠΏΡΡ ΠΎΠ»Π΅ΠΉ | |
| ES2363064T3 (es) | Tratamiento de cΓ‘nceres del cuerpo humano utilizando et743. | |
| NZ529801A (en) | Compositions and uses of ET743 for treating cancer |