药剂科 药物 Other Alkylating agents 达卡巴嗪/ Dacarbazine(DTC) Melanoma, Hodgkins disease, soft tissue sarcoma requires activation by liver microsomal system >铂类/ Platinum compounds DNA交联,抑制合成; iA/synergistic with other anticancer agents 卡铂/ Carboplatin( (less Gi and renal toxicity);可替代顺铂/ alternative to cisplatin 奥沙利铂/ oxaliplatin
药物 Other Alkylating agents ➢ 达卡巴嗪/Dacarbazine (DTIC) • Melanoma, Hodgkin's disease, soft tissue sarcoma • requires activation by liver microsomal system ➢ 铂类/Platinum compounds • DNA交联，抑制合成； • 联用/synergistic with other anticancer agents • 卡铂/Carboplatin (less GI and renal toxicity); 可替代顺铂/alternative to cisplatin • 奥沙利铂/oxaliplatin 11
药剂科 药物 抗代谢剂/ Antimetabolites 多为干扰核酸/核苷酸合成; 氨甲喋呤/ Methotrexate(MTX) 叶酸拮抗剂/ Folic acid antagonist;干扰二氢叶酸还原酶/ dihydrofolate reductase; 毒性:GI粘膜;骨髓抑制;皮肤;→解救:亚叶酸钙/ Leucovorin 嘌呤拮抗剂/ Purine antagonists 白血病/l eukemI 氟达拉滨/ Fludarabine 淋巴癌/ ymphoma; 吡啶拮抗剂/ Pyrimidine antagonists 氟尿嘧啶/ Flurouracil(5-FU; n;口腔粘膜炎/ mucositis 阿糖胞苷/ Cytarabine: almost exclusively for acute myelogenous leukemia o S phase-specific antimetabolite o Blocks DNA synthesis; no effect on RNA or protein synthesis 12 o严重的骨髓抑制;
药物 抗代谢剂/Antimetabolites ➢ 多为干扰核酸/核苷酸合成; ➢ 氨甲喋呤/Methotrexate (MTX) • 叶酸拮抗剂/Folic acid antagonist; 干扰二氢叶酸还原酶/dihydrofolate reductase; • 毒性：GI粘膜；骨髓抑制；皮肤；解救：亚叶酸钙/Leucovorin ➢ 嘌呤拮抗剂/Purine Antagonists • 白血病/leukemia; • 氟达拉滨/Fludarabine o 淋巴癌/lymphoma; ➢ 吡啶拮抗剂/Pyrimidine Antagonists • 氟尿嘧啶/Flurouracil (5-FU); o Myelosuppression；口腔粘膜炎/mucositis • 阿糖胞苷/Cytarabine：almost exclusively for acute myelogenous leukemia o S phase-specific antimetabolite； o Blocks DNA synthesis; no effect on RNA or protein synthesis o 严重的骨髓抑制； 12
药剂科 药物 植物生物碱/ Plant Alkaloids >长春花碱/ Vinblastine; 微管解聚/ microtubule depolymerization; arrest at M- phase 淋巴癌/ Lymphomas Nausea/vomiting BE#/alopecia; bone marrow suppression 长春新碱/ incristine 机制类 vinblastin; 联合强的松/ prednisone, acute leukemia〔 children) rapidly proliferating neoplasms 神经毒性反应 neurotoxic reactions;偶尔 bone marrow depression 白血病/ eukemia; 鬼臼毒素类/ Podophyllotoxins 依托泊苷/ Etoposide(P-16);替尼泊苷/ teniposide (vm-26 inhibition of topoisomerase II; arrest at late S-G2-phase; 13
药物 植物生物碱/Plant Alkaloids ➢ 长春花碱/Vinblastine; • 微管解聚/microtubule depolymerization；arrest at M-phase • 淋巴癌/Lymphomas • Nausea/vomiting；脱发/alopecia；bone marrow suppression ➢ 长春新碱/Vincristine • 机制类vinblastin; • 联合强的松/prednisone，acute leukemia (children) • rapidly proliferating neoplasms • 神经毒性反应neurotoxic reactions；偶尔bone marrow depression • 白血病/leukemia; ➢ 鬼臼毒素类/Podophyllotoxins • 依托泊苷/Etoposide (VP- 16); 替尼泊苷/teniposide (VM-26) • inhibition of topoisomerase II ；arrest at late S-G2-phase; 13
药剂科 药物 植物生物碱/ Plant Alkaloids >喜树碱/ Camptothecins; interfere with activity of topoisomerase i 拓扑替康/ Topotecan: 转移性卵巢癌 metastatic ovarian cancer 粒缺/ Neutropenia,血小板降低/ thrombocytopenia,贫血/ anemla 伊立替康/ Irinotecan: prodrug o colon and rectal cancer o R E/diarrhea; nausea/vomiting; DLT: myelosuppression 紫杉类/ Taxans Mitotic spindle inhibitor: enhances tubulin polymerization 紫杉醇/ paclitaxel 淋巴结阳性, o Ovarian, advanced breast cancer 阴性患者中使用存争议 Neutropenia, thrombocytopenia,外周神经毒性/ peripheral neuropathy 多西他赛/ docetaxel o bone marrow suppression
药物 植物生物碱/Plant Alkaloids ➢ 喜树碱/Camptothecins; • interfere with activity of topoisomerase I • 拓扑替康/Topotecan: o 转移性卵巢癌metastatic ovarian cancer o 粒缺/Neutropenia，血小板降低/thrombocytopenia，贫血/anemia • 伊立替康/Irinotecan: prodrug o colon and rectal cancer o 腹泻/diarrhea；nausea/vomiting；DLT: myelosuppression ➢ 紫杉类/Taxans • Mitotic spindle inhibitor: enhances tubulin polymerization ; • 紫杉醇/paclitaxel o Ovarian, Advanced breast cancer o Neutropenia, thrombocytopenia, 外周神经毒性/peripheral neuropathy • 多西他赛/docetaxel o bone marrow suppression 淋巴结阳性， 阴性患者中使用存争议 14
药剂科 药物 抗肿瘤抗生素/ Antibiotics 链霉素/ Streptomyces衍生物 DNA intercalation, blocking synthesis of DNA and rna 多柔比星,柔红霉素/ Doxorubicin, Daunorubicin hepatic metabolism; biliary excretion; enterohepatic recirculation Semiquinone free radical (may responsible for myocardial damage) 联用CTX,紫杉类,铂类; 乳腺癌,卵巢癌,淋巴癌等等 Bone marrow depression, irreversible cardiotoxicity. severe alopecia 丝裂霉素/ Mitomycin 代谢后激活产生烷化剂 宫颈鳞癌/ squamous cell carcinoma of the cerviⅸx;腺癌(肺、胃、胰腺) 多次给药后 severe myelosuppression,CINV,偶尔肾毒性/ nephrotoxicity 博莱霉素/ Bleomycin free radical formation; arrests division in G2; E* Vinblastine and cisplatin; 15
药物 抗肿瘤抗生素/Antibiotics ➢ 链霉素/Streptomyces衍生物 • DNA intercalation, blocking synthesis of DNA and RNA ➢ 多柔比星，柔红霉素/Doxorubicin, Daunorubicins • hepatic metabolism; biliary excretion; enterohepatic recirculation • Semiquinone free radical (may responsible for myocardial damage) • 联用CTX，紫杉类，铂类； • 乳腺癌，卵巢癌，淋巴癌等等 • Bone marrow depression, irreversible cardiotoxicity. severe alopecia ➢ 丝裂霉素/Mitomycin • 代谢后激活产生烷化剂 • 宫颈鳞癌/squamous cell carcinoma of the cervix；腺癌（肺、胃、胰腺） • 多次给药后severe myelosuppression, CINV，偶尔肾毒性/nephrotoxicity ➢ 博莱霉素/Bleomycin • free radical formation；arrests division in G2 ；联合vinblastine and cisplatin； 15