TWI791430B - 針對具有重度腎功能障礙之癌症患者之治療方法 - Google Patents
針對具有重度腎功能障礙之癌症患者之治療方法 Download PDFInfo
- Publication number
- TWI791430B TWI791430B TW106103736A TW106103736A TWI791430B TW I791430 B TWI791430 B TW I791430B TW 106103736 A TW106103736 A TW 106103736A TW 106103736 A TW106103736 A TW 106103736A TW I791430 B TWI791430 B TW I791430B
- Authority
- TW
- Taiwan
- Prior art keywords
- cancer
- ftd
- day
- patients
- days
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract description 47
- 201000011510 cancer Diseases 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title abstract description 19
- 206010062237 Renal impairment Diseases 0.000 title description 15
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229940109239 creatinine Drugs 0.000 claims abstract description 17
- KGHYQYACJRXCAT-UHFFFAOYSA-N tipiracil hydrochloride Chemical compound Cl.N1C(=O)NC(=O)C(Cl)=C1CN1C(=N)CCC1 KGHYQYACJRXCAT-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 16
- 229940124597 therapeutic agent Drugs 0.000 claims description 14
- 206010009944 Colon cancer Diseases 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 206010006187 Breast cancer Diseases 0.000 claims description 8
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- 208000002699 Digestive System Neoplasms Diseases 0.000 claims description 8
- 239000012830 cancer therapeutic Substances 0.000 claims description 8
- 208000024558 digestive system cancer Diseases 0.000 claims description 8
- 201000010231 gastrointestinal system cancer Diseases 0.000 claims description 8
- 239000002131 composite material Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 3
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims 3
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims 1
- 229940104230 thymidine Drugs 0.000 claims 1
- VSQQQLOSPVPRAZ-RRKCRQDMSA-N trifluridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 VSQQQLOSPVPRAZ-RRKCRQDMSA-N 0.000 abstract description 9
- 229940000425 combination drug Drugs 0.000 abstract 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 73
- 230000008085 renal dysfunction Effects 0.000 description 22
- 230000003907 kidney function Effects 0.000 description 15
- 230000000694 effects Effects 0.000 description 9
- -1 2-iminopyrrolidin-1-yl Chemical group 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 238000004364 calculation method Methods 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 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
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 101710132082 Pyrimidine/purine nucleoside phosphorylase Proteins 0.000 description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 102000013537 Thymidine Phosphorylase Human genes 0.000 description 2
- 238000011226 adjuvant chemotherapy Methods 0.000 description 2
- 239000003463 adsorbent Substances 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 239000002781 deodorant agent Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 201000004101 esophageal cancer Diseases 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 229960003943 hypromellose Drugs 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 206010038038 rectal cancer Diseases 0.000 description 2
- 201000001275 rectum cancer Diseases 0.000 description 2
- 230000000306 recurrent effect Effects 0.000 description 2
- 201000000849 skin cancer Diseases 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 1
- PLIXOHWIPDGJEI-OJSHLMAWSA-N 5-chloro-6-[(2-iminopyrrolidin-1-yl)methyl]-1h-pyrimidine-2,4-dione;1-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)pyrimidine-2,4-dione;hydrochloride Chemical compound Cl.N1C(=O)NC(=O)C(Cl)=C1CN1C(=N)CCC1.C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 PLIXOHWIPDGJEI-OJSHLMAWSA-N 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010004593 Bile duct cancer Diseases 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- SGHZXLIDFTYFHQ-UHFFFAOYSA-L Brilliant Blue Chemical compound [Na+].[Na+].C=1C=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C(=CC=CC=2)S([O-])(=O)=O)C=CC=1N(CC)CC1=CC=CC(S([O-])(=O)=O)=C1 SGHZXLIDFTYFHQ-UHFFFAOYSA-L 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- CIWBSHSKHKDKBQ-DUZGATOHSA-N D-araboascorbic acid Natural products OC[C@@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-DUZGATOHSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010061825 Duodenal neoplasm Diseases 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 206010054184 Small intestine carcinoma Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004376 Sucralose Substances 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 238000000418 atomic force spectrum Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 208000026900 bile duct neoplasm Diseases 0.000 description 1
- 201000009036 biliary tract cancer Diseases 0.000 description 1
- 208000020790 biliary tract neoplasm Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 229950008138 carmellose Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- GYOZYWVXFNDGLU-XLPZGREQSA-N dTMP Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)C1 GYOZYWVXFNDGLU-XLPZGREQSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 201000000312 duodenum cancer Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 235000010350 erythorbic acid Nutrition 0.000 description 1
- 239000004318 erythorbic acid Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000009760 functional impairment Effects 0.000 description 1
- 210000000232 gallbladder Anatomy 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N iron oxide Inorganic materials [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 1
- 229940026239 isoascorbic acid Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 229940024740 lonsurf Drugs 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 229960000869 magnesium oxide Drugs 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000008368 mint flavor Substances 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- NDLPOXTZKUMGOV-UHFFFAOYSA-N oxo(oxoferriooxy)iron hydrate Chemical compound O.O=[Fe]O[Fe]=O NDLPOXTZKUMGOV-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 201000002314 small intestine cancer Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 229940023144 sodium glycolate Drugs 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 229960003962 trifluridine Drugs 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Images
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
- A61K31/495—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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本發明提供一種具有重度腎功能障礙之癌症患者之癌症治療方法。 本發明之治療方法係對肌酸酐清除率為15 mL/min以上未達30 mL/min之患者之癌症治療方法,其包括:對於以莫耳比1:0.5含有α,α,α-三氟胸苷(FTD)及5-氯-6-[(2-亞胺基吡咯啶-1-基)甲基]嘧啶-2,4(1H,3H)-二酮鹽酸鹽之複合劑,將以FTD換算量計為30~50 mg/m2
/天之用量分為1天2~4次經口投予至上述患者。
Description
本發明係關於一種針對具有重度腎功能障礙之癌症患者之治療方法。
三氟尿苷(別名:α,α,α-三氟胸苷。以下,亦稱為「FTD」)藉由利用胸苷酸生成抑制作用獲得之DNA合成抑制及由向DNA中之取入獲得之DNA功能障礙而發揮抗腫瘤效果。另一方面,地匹福林鹽酸鹽(化學名:5-氯-6-[(2-亞胺基吡咯啶-1-基)甲基]嘧啶-2,4(1H,3H)-二酮鹽酸鹽。以下,亦稱為「TPI」)具有胸苷磷酸化酶抑制作用。已知有藉由TPI抑制因胸苷磷酸化酶引起之FTD於活體內之分解,而增強FTD之抗腫瘤效果(專利文獻1)。目前,以莫耳比1:0.5含有FTD及TPI之複合劑(以下,亦稱為「FTD-TPI複合劑」)正作為實體癌之治療劑進行開發,在美國,作為進展、復發之結腸直腸癌之治療劑,作為商品名Lonsurf之複合錠得到批准(非專利文獻1及2)。臨床中之FTD-TPI複合劑之用法用量被定義為:通常對於成人而言,以體表面積為基準,將以FTD計為70 mg/m2
/天按1天2次,連續經口投予5天之後停藥2天。將此重複2次之後停藥14天。將此作為1週期反覆投予。 FTD-TPI複合劑由於TPI係腎排泄型藥劑,因此理論上認為於向腎功能降低之患者投予之情形時,有使FTD之暴露增加之可能性。即使於臨床試驗中,以FTD-TPI複合劑投予患者之肌酸酐清除率(以下,亦稱為「CLcr」)值為基礎來比較腎功能障礙之外之有害現象表現率,結果確認,關於與骨髄抑制相關之副作用(血小板數減少、紅血球數減少、血紅蛋白減少、嗜中性球數減少)之表現率,與腎功能正常(CLcr:≧90 mL/min)相比,輕度腎功能障礙(CLcr:60-89 mL/min)及中度腎功能障礙(CLcr:30-59 mL/min)有更高之傾向。該患者之肌酸酐清除率(CLcr)值係使用Cockcroft-Gault式算出,且根據美國食品及藥物管理局(FDA;Food and Drug Administration)之手冊(針對具有腎功能障礙之患者中工業藥物動力學指導原則-研究設計、資料分析以及對劑量及標記之影響,Guidance for Industry Pharmacokinetics in Patients with Impaired Renal Function-Study Design, Data Analysis, and Impact on Dosing and Labeling)之腎功能分類基準而分類者。因此,關於具有重度腎功能障礙之患者(CLcr:15~29 mL/min)被視為藥品仿單標示外,即使於迄今進行之臨床試驗中仍未對該患者投予FTD-TPI複合劑,完全未有關於安全性、有效性之資訊。 一般而言,對腎功能障礙患者之藥物投予必須根據腎功能之程度調節投予量或投予間隔,推薦根據上述FDA手冊,基於藥物動力學(PK)而選擇用量。 然而,針對具有重度腎功能障礙之癌症患者,難以進行更安全、且有效性更高之癌症治療。 [先前技術文獻][專利文獻] [專利文獻1]國際公開第1996/30346號 [非專利文獻] [非專利文獻1]Invest New Drugs 26 (5): 445 - 54, 2008 [非專利文獻2]Lancet Oncol.13 (10): 993 - 1001, 2012
[發明所欲解決之問題] 本發明係關於提供一種具有重度腎功能障礙之癌症患者之癌症治療方法。 [解決問題之技術手段] 本發明人針對CLcr為15~29 mL/min之具有重度腎功能障礙之癌症患者嘗試利用FTD-TPI複合劑進行癌症治療,結果發現:若將以FTD換算量計為1天30~50 mg/m2
之用量分為1天2~4次經口投予,則避免嚴重之副作用,並且確認出顯著之抗癌效果。 即,本發明係提供以下之發明[1]~[28]者。 [1]一種治療方法,其係對肌酸酐清除率未達30 mL/min之患者之癌症治療方法,其包括:對於以莫耳比1:0.5含有α,α,α-三氟胸苷(FTD)及5-氯-6-[(2-亞胺基吡咯啶-1-基)甲基]嘧啶-2,4(1H,3H)-二酮鹽酸鹽之複合劑,將以FTD換算量計為30~50 mg/m2
/天之用量分為1天2~4次經口投予至上述患者。 [2]如[1]記載之癌症治療方法,其中患者係肌酸酐清除率為15 mL/min以上且29 mL/min以下之患者。 [3]如[1]或[2]記載之癌症治療方法,其中將以FTD換算量計為40 mg/m2
/天之用量分為1天2次經口投予。 [4]如[1]至[3]中任一項記載之癌症治療方法,其中投予排程係每週連續經口投予5天並停藥2天。 [5]如[1]至[4]中任一項記載之癌症治療方法,其中投予排程係將連續經口投予5天並停藥2天重複2次之後停藥14天。 [6]如[1]至[5]中任一項記載之癌症治療方法,其中癌症為消化系統癌或乳腺癌。 [7]如[1]至[6]中任一項記載之癌症治療方法,其中癌症為大腸癌。 [8]一種治療劑,其係對肌酸酐清除率未達30 mL/min之患者之癌症治療劑,且對於以莫耳比1:0.5含有α,α,α-三氟胸苷(FTD)及5-氯-6-[(2-亞胺基吡咯啶-1-基)甲基]嘧啶-2,4(1H,3H)-二酮鹽酸鹽之複合劑,將以FTD換算量計為30~50 mg/m2
/天之用量分為1天2~4次經口投予至上述患者。 [9]如[8]記載之癌症治療劑,其中患者係肌酸酐清除率為15 mL/min以上且29 mL/min以下之患者。 [10]如[8]或[9]記載之癌症治療劑,其中將以FTD換算量計為40 mg/m2
/天之用量分為1天2次經口投予。 [11]如[8]至[10]中任一項記載之癌症治療劑,其中投予排程係每週連續經口投予5天並停藥2天。 [12]如[8]至[11]中任一項記載之癌症治療劑,其中投予排程係將連續經口投予5天並停藥2天重複2次之後停藥14天。 [13]如[8]至[12]中任一項記載之癌症治療劑,其中癌症為消化系統癌或乳腺癌。 [14]如[8]至[13]中任一項記載之癌症治療劑,其中癌症為大腸癌。 [15]一種複合劑之用途,該複合劑係用於製造肌酸酐清除率未達30 mL/min之患者之癌症治療劑,且以莫耳比1:0.5含有α,α,α-三氟胸苷(FTD)及5-氯-6-[(2-亞胺基吡咯啶-1-基)甲基]嘧啶-2,4(1H,3H)-二酮鹽酸鹽;並且對於上述複合劑,將以FTD換算量計為30~50 mg/m2
/天之用量分為1天2~4次經口投予至上述患者。 [16]如[15]記載之用途,其中患者係肌酸酐清除率為15 mL/min以上且29 mL/min以下之患者。 [17]如[15]或[16]記載之用途,其中將以FTD換算量計為40 mg/m2
/天之用量分為1天2次經口投予。 [18]如[15]至[17]中任一項記載之用途,其中投予排程係每週連續經口投予5天並停藥2天。 [19]如[15]至[18]中任一項記載之用途,其中投予排程係將連續經口投予5天並停藥2天重複2次之後停藥14天。 [20]如[15]至[19]中任一項記載之用途,其中癌症為消化系統癌或乳腺癌。 [21]如[15]至[20]中任一項記載之用途,其中癌症為大腸癌。 [22]一種複合劑,其用於肌酸酐清除率未達30 mL/min之患者之癌症治療,且以莫耳比1:0.5含有α,α,α-三氟胸苷(FTD)及5-氯-6-[(2-亞胺基吡咯啶-1-基)甲基]嘧啶-2,4(1H,3H)-二酮鹽酸鹽,並且將以FTD換算量計為30~50 mg/m2
/天之用量分為1天2~4次經口投予至上述患者。 [23]如[22]記載之複合劑,其中患者係肌酸酐清除率為15 mL/min以上且29 mL/min以下之患者。 [24]如[22]或[23]記載之複合劑,其中將以FTD換算量計為40 mg/m2
/天之用量分為1天2次經口投予。 [25]如[22]至[24]中任一項記載之複合劑,其中投予排程係每週連續經口投予5天並停藥2天。 [26]如[22]至[25]中任一項記載之複合劑,其中投予排程係將連續經口投予5天並停藥2天重複2次之後停藥14天。 [27]如[22]至[26]中任一項記載之複合劑,其中癌症為消化系統癌或乳腺癌。 [28]如[22]至[27]中任一項記載之複合劑,其中癌症為大腸癌。 [發明之效果] 根據本發明之治療方法,在不使嚴重之副作用發作之情況下,獲得具有重度腎功能障礙之癌症患者之優異之癌症治療效果。
於本發明中,使用以莫耳比1:0.5含有α,α,α-三氟胸苷及5-氯-6-[(2-亞胺基吡咯啶-1-基)甲基]嘧啶-2,4(1H,3H)-二酮鹽酸鹽之複合劑。 FTD及TPI分別為公知之化合物,例如能夠按照國際公開第1996/30346號說明書所記載之方法合成。又,FTD-TPI複合劑亦為公知(非專利文獻1及2)。又,在美國,錠劑形態之FTD-TPI複合劑作為進展、復發之結腸直腸癌之治療劑得到批准。 於本發明所使用之FTD-TPI複合劑只要為能夠經口投予之形態即可。例如,可列舉錠劑、包衣錠劑、丸劑、散劑、顆粒劑、膠囊劑、液劑、懸浮劑、乳劑等。該等製劑可使用藥學上容許之載體等,藉由該領域中通常已知之慣用製劑化方法而進行製劑化。 又,FTD-TPI複合劑亦可以將30~50 mg/m2
/天之用量分為1天2~4次投予之方式進行適當分割而包裝。作為包裝方法,只要為該領域中通常已知之慣用包裝方法則無特別限制,例如,若為錠劑,則可將其包裝於保護其免受濕氣及氧影響之包裝用材料中。 作為藥學上容許之載體,例如可例示於通常之藥劑所通用之各種載體,例如賦形劑、黏結劑、崩解劑、潤滑劑、崩解防止劑、吸收促進劑、保濕劑、吸附劑、塗佈劑、溶劑、助溶劑、懸浮劑、等張劑、pH值調整劑、緩衝劑、穩定劑、著色劑、矯味劑、除臭劑等。 作為賦形劑,可列舉:乳糖、白糖、D-甘露醇、澱粉、結晶纖維素、矽酸鈣等。作為黏結劑,可列舉:羥丙基纖維素、甲基纖維素、聚乙烯吡咯啶酮、飴粉、羥丙甲纖維素等。作為崩解劑,可列舉澱粉、乙醇酸鈉、羧甲基纖維素鈣、交聯羧甲基纖維素鈉、交聯聚維酮、低取代羥丙基纖維素、部分α化澱粉等。作為潤滑劑,可列舉:滑石、硬脂酸鎂、蔗糖脂肪酸酯、硬脂酸、反丁烯二酸硬脂酯鈉等。作為崩解防止劑,可列舉:白糖、硬脂酸、可可脂、氫化油等。作為吸收促進劑,可列舉:四級銨鹽基、月桂基硫酸鈉等。作為保濕劑,可列舉:甘油、澱粉等。作為吸附劑,可列舉:澱粉、乳糖、高嶺土、膨潤土、膠體狀矽酸等。作為塗佈劑,可列舉:乙基纖維素、甲基丙烯酸胺基烷基酯共聚物RS、羥丙甲纖維素、白糖等。作為溶劑,可列舉:水、丙二醇、生理鹽水。作為助溶劑,可列舉:聚乙二醇、乙醇、α-環糊精、聚乙二醇400、聚山梨糖醇酯80等。作為懸浮劑,可列舉:鹿角菜膠、結晶纖維素-羧甲基纖維素鈉、聚氧乙烯氫化蓖麻油。作為等張劑,可列舉:氯化鈉、甘油、氯化鉀等。作為pH值調整劑、緩衝劑,可列舉:檸檬酸鈉、鹽酸、乳酸、磷酸、磷酸二氫鈉等。作為穩定劑,可列舉:焦亞硫酸鈉、乙二胺四乙酸鈉、異抗壞血酸、氧化鎂、二丁基羥基甲苯等。作為著色劑,可列舉:氧化鈦、三氧化二鐵、食用藍色1號、葉綠素銅等。作為矯味、除臭劑,可列舉:阿斯巴甜、糖精、蔗糖素、1-薄荷腦、薄荷香料等。 於本發明中,FTD-TPI複合劑係將以FTD換算量計為30~50 mg/m2
/天之用量分為1天2~4次經口投予。 FTD-TPI複合劑之用量以FTD換算量計為30~50 mg/m2
/天,較佳為30~48 mg/m2
/天,較佳為35~45 mg/m2
/天,較佳為40 mg/m2
/天。 又,每天之投予次數為2~4次,較佳為2~3次,更佳為2次。 投予與投予之間隔較佳為間隔6小時以上。 此處,對患者之投予量係根據由患者之身高及體重算出之體表面積(BSA)所決定。作為體表面積之計算方法,根據患者之種族、性別、健康狀態、症狀等適當使用慣用之方法,例如可列舉如下述1~6之計算式,較佳為下述1或2(a)。 1. Mosteller公式(參照N Engl J Med 1987 Oct 22; 317(17): 1098(letter)) BSA(m2
)=([身高(cm)×體重(kg)]/3600)1/2
2. DuBois及DuBois公式(參照Arch Int Med 1916 17:863-71; J Clin Anesth.1992; 4(1):4-10) (a) BSA(m2
)=0.20247×身高(m)0.725
×體重(kg)0.425
(b) BSA(m2
)=0.007184×身高(cm)0.725
×體重(kg)0.425
3. Haycock公式(參照The Journal of Pediatrics 1978 93: 1: 62-66) BSA(m2
)=0.024265×身高(cm)0.3964
×體重(kg)0.5378
4. Gehan及George公式(參照Cancer Chemother Rep 1970 54:225-35) BSA(m2
)=0.0235×身高(cm)0.42246
×體重(kg)0.51456
5. Boyd公式(參照Minneapolis : university of Minnesota Press, 1935) BSA(m2
)=0.0003207×身高(cm)0.3
×體重(grams)(0.7285 - (0.0188 x LOG (grams))
6. Fujimoto公式(參照日本醫學雜誌,1968 23(5):443-450) BSA(m2
)=0.008883×身高(cm)0.663
×體重(kg)0.444
例如,於使用上述1之計算式計算身高175 cm、體重70 kg之癌症患者之體表面積之情形時,體表面積算出為([175(cm)×70(kg)]/ 3600)1/2
=1.84(m2
)。於對於該患者將投予量以FTD換算量計設為50 mg/m2
/天之情形時,成為1.84×50=92 mg,1天共計投予量被設定為92 mg。 於本發明中,投予對象者為CLcr未達30 mL/min之癌症患者。更佳為15 mL/min以上、未達30 mL/min之癌症患者。特佳為15 mL/min以上且29 mL/min以下之癌症患者。 患者之CLcr值係腎功能之指標,CLcr為15~29 mL/min之患者包括具有重度腎功能障礙之患者(重度腎功能障礙患者)。重度腎功能障礙患者亦指高度腎功能障礙患者。 於本發明中,CLcr係使用如下所示之Cockcroft-Gault式而算出。 [Cockcroft-Gault式] 男性:CLcr(mL/min)={(140-年齡)×體重(kg)}÷{血清肌酸酐值(mg/dL)×72} 女性:CLcr(mL/min)={(140-年齡)×體重(kg)}÷{血清肌酸酐值(mg/dL)×72}×0.85 再者,血清肌酸酐值能夠藉由慣例進行測定。 於本發明中,投予排程較佳為每週連續經口投予5天之後停藥2天。又,較佳為將連續經口投予5天並停藥2天重複2次之後停藥14天,將此作為1週期反覆投予。 關於成為本發明之治療方法之對象之癌症,例如可列舉:頭頸部癌、消化系統癌(食道癌、胃癌、十二指腸癌、肝癌、膽道癌(膽囊、膽管癌等)、胰腺癌、小腸癌、大腸癌(結腸直腸癌、結腸癌、直腸癌等)等)、肺癌(非小細胞肺癌、小細胞肺癌)、乳腺癌、卵巢癌、子宮癌(子宮頸癌、子宮體癌等)、腎癌、膀胱癌、前列腺癌、皮膚癌等。再者,其中於癌症中不僅包括原發病灶,亦包括轉移至其他器官(肝等)之癌症。其中,就抗腫瘤效果及副作用之觀點而言,較佳為頭頸部癌、消化系統癌、肺癌、乳腺癌、腎癌、皮膚癌,更佳為消化系統癌或乳腺癌,更佳為食道癌、大腸癌、胃癌,特佳為大腸癌。又,本發明之治療方法可為利用外科手段摘除腫瘤後旨在防止復發而進行之術後輔助化學療法,亦可為旨在利用外科手段摘除腫瘤而預先進行之術前輔助化學療法。 [實施例]繼而列舉實施例進一步詳細地說明本發明,但本發明並不受該等實施例任何限定,在本發明之技術思想內於本領域具有通常之知識者能夠進行大量之變化。(實施例1)對具有重度腎功能障礙之癌症患者之投予量之推定研究了以包含結腸/直腸癌之實體癌之患者為對象進行治療時之FTD之藥物動力學,該治療如下:將FTD-TPI複合劑(FTD與TPI之莫耳比為1:0.5之混合物)以1次35 mg/m2
(以FTD計,以下相同)1天2次連續經口投予5天並停藥2天,將此投予排程重複2次之後停藥14天,將此作為1週期反覆進行。患者於投予開始前藉由上述Cockcroft-Gault式算出CLcr之值而評估腎功能,按對照組(正常,CLcr:≧90 mL/min)、輕度(CLcr:60~89 mL/min)、中度(CLcr:30~59 mL/min)進行分組。於FTD-TPI複合劑投予後第1天及第12天之投予前及投予後0.5、1、2、4、6、8、10、12小時實施採血,測定血漿中FTD及TPI濃度。使用所得之血漿中濃度算出FTD及TPI之藥物動力學參數,將結果於表1表示。[表1]FTD及TPI之藥物動力學參數(群0:正常,群1:輕度腎功能障礙,群2:中度腎功能障礙)
於FTD-TPI複合劑中FTD係顯現抗癌活性之活性本體,TPI係使FTD之血漿中濃度上升之調節物。因此,反覆投予後之FTD血漿中濃度與FTD-TPI複合劑之效果及安全性有最強關聯。與腎功能正常患者相比,於輕度腎功能障礙患者(群1)中FTD之AUC0-12
高約16%,於中度腎功能障礙患者(群2)中高約51%,因此提示出,由於與腎功能之降低之同時FTD之AUC上升,故而必須對重度腎功能障礙患者減少FTD-TPI複合劑之投予量。FTD之消失半衰期於輕度腎功能障礙患者為2.40小時,於中度腎功能障礙患者為3.22小時,與腎功能正常患者之2.09小時相比,未見有較大之延長。由於FTD之半衰期之長度與一天投予兩次時之投予間隔12小時相比足夠短,因此能夠在不變更投予間隔之情況下,藉由減量至適當之投予量而維持FTD-TPI複合劑之效果。 為了決定對於重度腎功能障礙患者之適當之投予量,進行投予後第12天之FTD之經口清除率(CL/F)與肌酸酐清除率(CLcr)之回歸分析。將結果示於圖1。 如圖1,兩參數之關係能夠藉由以下之檢定力曲線而近似。 FTD CL/F (L/hr)=0.3432×CLcr(mL/min)0.4870
使用本回歸方程式,根據CLcr算出各腎功能障礙等級中之FTD之CL/F,進一步算出FTD之AUC相對於腎功能正常患者之比率,將該等之結果示於表2。此時,將腎功能正常患者之CLcr之中央值(109 mL/min)作為對照(1.00)算出比率。提示如下:向重度腎功能障礙患者以15 mg/m2
、20 mg/m2
及25 mg/m2
投予FTD-TPI複合劑時之FTD之AUC與分別向腎功能正常患者、輕度腎功能障礙患者、中度腎功能障礙患者投予35 mg/m2
時之AUC類似。另一方面,認為於向重度腎功能障礙患者直接以35 mg/m2
投予FTD-TPI複合劑之情形時FTD之AUC上升至腎功能正常患者之2倍以上。[表2]由檢定力回歸方程式所推定之FTD經口清除率之範圍及各用量中之AUC之範圍
於本試驗之安全性效果中,腎功能正常患者、輕度腎功能障礙患者、中度腎功能障礙患者均能夠容許FTD-TPI複合劑之35 mg/m2
。因此,向重度腎功能障礙患者以15 mg/m2
、20 mg/m2
及25 mg/m2
投予FTD-TPI複合劑時之FTD之AUC均為能夠容許之等級。但是,投予15 mg/m2
時之FTD之AUC低於腎功能正常患者之AUC,而有效果減弱之可能性。另一方面,由於重度腎功能障礙患者之腎功能不穩定,因此於投予25 mg/m2
之情形時有FTD之AUC超出預測之可能性。根據該等情況,對於重度腎功能障礙患者(CLcr:15~29 mL/min),FTD-TPI複合劑最佳為以20 mg/m2
進行投予。 藉由對於重度腎功能障礙患者將FTD-TPI複合劑減量至以FTD換算量計為30~50 mg/m2
/天之投予量,尤其減量至以FTD換算量計為40 mg/m2
/天之投予量,從而能夠維持安全性之同時期待奏效。
圖1係表示投予後第12天之肌酸酐清除率與FTD之經口清除率之關係之圖。
Claims (6)
- 一種複合劑之用途,該複合劑用於製造肌酸酐清除率為15mL/min以上且29mL/min以下之患者之癌症治療劑,且以莫耳比1:0.5含有α,α,α-三氟胸苷(FTD)及5-氯-6-[(2-亞胺基吡咯啶-1-基)甲基]嘧啶-2,4(1H,3H)-二酮鹽酸鹽;並且對於上述複合劑,將以FTD換算量計為30~50mg/m2/天之用量分為1天2~4次經口投予至上述患者。
- 如請求項1之用途,其中將以FTD換算量計為40mg/m2/天之用量分為1天2次經口投予。
- 如請求項1之用途,其中投予排程係每週連續經口投予5天並停藥2天。
- 如請求項1之用途,其中投予排程係將連續經口投予5天並停藥2天重複2次之後停藥14天。
- 如請求項1至4中任一項之用途,其中癌症為消化系統癌或乳腺癌。
- 如請求項1至4中任一項之用途,其中癌症為大腸癌。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662291799P | 2016-02-05 | 2016-02-05 | |
US62/291,799 | 2016-02-05 |
Publications (2)
Publication Number | Publication Date |
---|---|
TW201728328A TW201728328A (zh) | 2017-08-16 |
TWI791430B true TWI791430B (zh) | 2023-02-11 |
Family
ID=59501005
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
TW106103736A TWI791430B (zh) | 2016-02-05 | 2017-02-03 | 針對具有重度腎功能障礙之癌症患者之治療方法 |
Country Status (12)
Country | Link |
---|---|
US (4) | US10456399B2 (zh) |
EP (1) | EP3412295A4 (zh) |
JP (3) | JP6882205B2 (zh) |
KR (2) | KR102298144B1 (zh) |
AU (1) | AU2017215825B9 (zh) |
MA (1) | MA43977A (zh) |
NZ (1) | NZ745113A (zh) |
RU (1) | RU2727598C2 (zh) |
TW (1) | TWI791430B (zh) |
UA (1) | UA123403C2 (zh) |
WO (1) | WO2017135412A1 (zh) |
ZA (1) | ZA201805245B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017135412A1 (ja) * | 2016-02-05 | 2017-08-10 | 大鵬薬品工業株式会社 | 重度腎機能障害を有する癌患者に対する治療方法 |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100424934B1 (ko) | 1995-03-29 | 2004-07-27 | 다이호야쿠힌고교 가부시키가이샤 | 우라실유도체및이를함유하는항종양효과증강제및항종양제 |
US7799783B2 (en) * | 2005-01-26 | 2010-09-21 | Taiho Pharmaceutical Co., Ltd. | Method of administrating an anticancer drug containing α, α, α-trifluorothymidine and thymidine phosphorylase inhibitor |
AU2006209547C1 (en) * | 2005-01-26 | 2022-04-07 | Taiho Pharmaceutical Co., Ltd. | Anticancer drug containing alpha,alpha,alpha-trifluorothymidine and thymidine phosphorylase inhibitor |
KR101693090B1 (ko) * | 2011-08-16 | 2017-01-04 | 다이호야쿠힌고교 가부시키가이샤 | Kras 유전자 변이형의 결장 직장암 환자에 대한 항종양제 및 치료 효과 예측 방법 |
JP5976923B2 (ja) * | 2013-03-27 | 2016-08-24 | 大鵬薬品工業株式会社 | イリノテカン塩酸塩水和物を含有する抗腫瘍剤 |
KR101928618B1 (ko) * | 2013-05-17 | 2018-12-12 | 다이호야쿠힌고교 가부시키가이샤 | Tk1 단백질의 발현이 항진된 결장직장암 환자에 대한 치료효과 예측 방법 |
CN106333952A (zh) | 2014-02-19 | 2017-01-18 | 齐鲁制药有限公司 | 一种胸苷磷酸化酶抑制剂的结晶形式及其制备方法 |
WO2017135412A1 (ja) * | 2016-02-05 | 2017-08-10 | 大鵬薬品工業株式会社 | 重度腎機能障害を有する癌患者に対する治療方法 |
-
2017
- 2017-02-03 WO PCT/JP2017/003994 patent/WO2017135412A1/ja active Application Filing
- 2017-02-03 JP JP2017565650A patent/JP6882205B2/ja active Active
- 2017-02-03 KR KR1020187025365A patent/KR102298144B1/ko active IP Right Grant
- 2017-02-03 TW TW106103736A patent/TWI791430B/zh active
- 2017-02-03 RU RU2018131573A patent/RU2727598C2/ru active
- 2017-02-03 KR KR1020217027596A patent/KR102412690B1/ko active IP Right Grant
- 2017-02-03 MA MA043977A patent/MA43977A/fr unknown
- 2017-02-03 NZ NZ745113A patent/NZ745113A/en unknown
- 2017-02-03 UA UAA201809086A patent/UA123403C2/uk unknown
- 2017-02-03 AU AU2017215825A patent/AU2017215825B9/en active Active
- 2017-02-03 EP EP17747563.9A patent/EP3412295A4/en active Pending
-
2018
- 2018-08-03 US US16/054,073 patent/US10456399B2/en active Active
- 2018-08-03 ZA ZA201805245A patent/ZA201805245B/en unknown
-
2019
- 2019-09-18 US US16/574,180 patent/US10960004B2/en active Active
-
2021
- 2021-03-02 US US17/190,068 patent/US20210177850A1/en not_active Abandoned
- 2021-05-06 JP JP2021078476A patent/JP2021113228A/ja active Pending
-
2023
- 2023-03-03 JP JP2023032977A patent/JP2023065622A/ja active Pending
-
2024
- 2024-01-09 US US18/407,514 patent/US20240148730A1/en active Pending
Also Published As
Publication number | Publication date |
---|---|
EP3412295A4 (en) | 2019-09-25 |
RU2018131573A3 (zh) | 2020-03-05 |
KR102298144B1 (ko) | 2021-09-03 |
JP6882205B2 (ja) | 2021-06-02 |
EP3412295A1 (en) | 2018-12-12 |
US20200030329A1 (en) | 2020-01-30 |
AU2017215825B9 (en) | 2020-11-26 |
JPWO2017135412A1 (ja) | 2018-12-06 |
RU2727598C2 (ru) | 2020-07-22 |
US20180338976A1 (en) | 2018-11-29 |
US10456399B2 (en) | 2019-10-29 |
ZA201805245B (en) | 2019-10-30 |
US20210177850A1 (en) | 2021-06-17 |
RU2018131573A (ru) | 2020-03-05 |
US10960004B2 (en) | 2021-03-30 |
KR20210111348A (ko) | 2021-09-10 |
JP2023065622A (ja) | 2023-05-12 |
JP2021113228A (ja) | 2021-08-05 |
AU2017215825B2 (en) | 2020-09-10 |
WO2017135412A1 (ja) | 2017-08-10 |
TW201728328A (zh) | 2017-08-16 |
NZ745113A (en) | 2021-12-24 |
KR102412690B1 (ko) | 2022-06-23 |
UA123403C2 (uk) | 2021-03-31 |
AU2017215825A1 (en) | 2018-08-23 |
US20240148730A1 (en) | 2024-05-09 |
MA43977A (fr) | 2018-12-12 |
KR20180104744A (ko) | 2018-09-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5576591B2 (ja) | α,α,α−トリフルオロチミジンとチミジンホスホリラーゼ阻害剤とを配合した抗癌剤 | |
US7799783B2 (en) | Method of administrating an anticancer drug containing α, α, α-trifluorothymidine and thymidine phosphorylase inhibitor | |
US20240148730A1 (en) | Method for treating cancer patients with severe renal impairment | |
JP2010106019A (ja) | リマプロストを含有してなる癌化学療法に起因する末梢神経障害予防、治療および/または症状軽減剤 | |
JP6458007B2 (ja) | 抗腫瘍性白金錯体を含有する抗腫瘍剤及び抗腫瘍効果増強剤 | |
JP4091639B2 (ja) | チロシンキナーゼ阻害剤が惹起する皮膚障害の予防剤および/または処置剤 | |
US20240122937A1 (en) | Treating cancer in patient with pten inactivating mutation | |
TW202245780A (zh) | 用於治療神經膠質母細胞瘤之方法 | |
JP2015199676A (ja) | レゴラフェニブを含有する抗腫瘍剤及び抗腫瘍効果増強剤 | |
WO2012105486A1 (ja) | 1日1回隔日投与を特徴とするテガフール含有組成物 | |
JP2003300888A (ja) | 抗腫瘍効果増強剤 |