Cisplatin Bleomycin

Cisplatin has major antitumor activity in a broad range of solid tumors, including non-small cell and small cell lung cancer, esophageal and gastric cancer, head and neck cancer, and genitourinary cancers, particularly testicular, ovarian, and bladder cancer. When used in combination regimens with vinblastine and bleomycin or etoposide and bleomycin, cisplatin-based therapy has led to the cure of nonseminomatous testicular cancer. 

Production of reactive chemicals that trap the anticancer drug Alkylators, bleomycin, cisplatin, doxorubicin... 

Some evidence su ests ondansetron may modestly affect the pharmacokinetics of cyclophosphamide and cisplatin but it does not appear to affect those of carmustine. Ondansetron did not affect the in vitro activity of epirubicin, bleomycin, cisplatin or es-tramustine. Cisplatin and fluorouracil do not affect the pharmacokinetics of ondansetron. In in vitro studies granisetron potentiated the cytotoxic effects of epirubicin, had an additive effect on bleomycin and estramustine activity and appeared not to affect the metabolism of docetaxel and paclitaxel. 

Renal excretion accounts for almost half of the total body clearance of bleomycin. Cisplatin is nephrotoxic and reduces the glomerular filtration rate so that the clearance of bleomycin is reduced. The accumulating bleomycin apparently causes the pulmonary toxicity. 

Five patients (aged 23 to 58) treated for germ cell tumours died from unexpected acute life-threatening vascular events (myocardial infarction, rectal infarction, cerebrovascular accident) after treatment with VBP (vinblastine, bleomycin, cisplatin). A survey of the literature by the authors of this paper revealed 14 other cases of both acute and long-term cardiovascular problems (myocardial infarction, coronary heart disease, cerebrovascular accident) in patients given VBP. ... 

Plasma digoxin levels may decrease when the drug is administered with bleomycin. When bleomycin is used witii cisplatin, there is an increased risk of bleomycin toxicity Pulmonary toxicity may occur when bleomycin is administered with other antineoplastic drugs. Plicamycin, mitomycin, mitoxantrone, and dactino-mycin have an additive bone marrow depressant effect when administered with other antineoplastic drugs. In addition, mitomycin, mitoxantrone, and dactinomycin decrease antibody response to live virus vaccines. Dactinomycin potentiates or reactivates skin or gastrointestinal reactions of radiation therapy There is an increased risk of bleeding when plicamycin is administered witii aspirin, warfarin, heparin, and the NSAIDs. 

Intraperitoneal administration of chemotherapeutic agents has been used for many years as a way of increasing the delivery of drugs to tumors (e.g., ovarian carcinoma) located in the peritoneal cavity (Markman, 1986 Howell and Zimra, 1988). Cisplatin (Casper et al., 1983 Markman et al., 1985), cytosine arabinoside (Ara-C) (King et al., 1984 Markman et al., 1985, 1986), and bleomycin (Markman et al., 1986) are examples of intraperitoneally administered drugs which were already successfully applied in clinical settings. 

C = Cisplatin, B = bleomycin, V = vindesine, F = 5-fluorouracil, S = surgery, See = squamous cell carcinoma, A = adenocarcinoma. 

Roth JA, Pass HI, Flanagan MM, Graeber GM, Rosenberg JC, Steinberg S. Randomized clinical trial of preoperative and postoperative adjuvant chemotherapy with cisplatin, vindesine, and bleomycin for carcinoma of the esophagus. J Thorac Cardiovasc Surg 1988 96(2) 242-248. 

B = bleomycin, C = chlorambucil, CT = chemotherapy, DFS = disease-free survival, Ep = epirubicin, F = fluorouracil, I = ifosfamide, M = mitomycin C, Mtx = methotrexate, O = vincristine, OS = overall survival, P = cisplatin, RT = radiation therapy, V = vinblastine. 

Intracavitary administration of various agents has been used for patients with malignant pleural or peritoneal effusions. Intraperitoneal instillations of cisplatin, etoposide, bleomycin, 5-fluorouracil, and interferon are well tolerated and are being evaluated in patients with ovarian carcinomas, in whom the tumor is frequently restricted to the peritoneal cavity. 

C. The dose-limiting toxicity of bleomycin is pulmonary toxicity and that of cisplatin is renal. Doxorubicin produces cardiotoxicity hematoxicity is dose limiting for methotrexate. 

Bleomycin, in combination with cisplatin or etopo-side, is important as part of the potentially curative combination chemotherapy of advanced testicular carcinomas. Bleomycin is used in some standard regimens for the treatment of Hodgkin s and non-Hodgkin s lymphomas, and it is useful against squamous cell carcinomas of the head and neck, cervix, and skin. 

Cisplatin, combined with bleomycin and vinblastine or etoposide, produces cures in most patients with metastatic testicular cancer or germ cell cancer of the ovary. Cisplatin also shows some activity against carcinomas of the head and neck, bladder, cervix, prostate, and lung. 

PCV Procarbazine, lomustine, vincristine PEB Cisplatin (platinum), etoposide, bleomycin... 

BEP Bleomycin, etoposide, cisplatin (Platinol) Germ cell tumors... 

Oxidative stress reduces the rate of cell proliferation, and that occurring during chemotherapy may interfere with the cytotoxic effects of antineoplastic drugs, which depend on rapid proliferation of cancer cells for optimal activity. Antioxidants detoxify ROS and may enhance the anticancer effects of chemotherapy. For some supplements, activities beyond their antioxidant properties, such as inhibition of topoisomerase II or protein tyrosine kinases, may also contribute. ROS cause or contribute to certain side effects that are common to many anticancer drugs, such as gastrointestinal toxicity and muagenesis. ROS also contribute to side effects that occur only with individual agents, such as doxorubicin-induced cardiotoxicity, cisplatin-induced nephrotoxicity, and bleomycin-induced pulmonary fibrosis. Antioxidants can reduce or prevent many of these side effects, and for some supplements the protective effect results from activities other than their antioxidant properties. Certain side effects, however, such as alopecia and myelosuppression, are not prevented... 

In vitro studies with several tumor cell lines have shown vitamin C to enhance the cytotoxic activity of doxorubicin, cisplatin, paclitaxel, dacarbazine, 5-FU, and bleomycin. Vitamin C has also been shown to increase drug accumulation and to partially reverse vincristine resistance of human nonsmall-cell lung cancer cells. 

P-Carotene has been shown to enhance the cytotoxicity of melphalan and BCNU on human squamous carcinoma cells and of cisplatin and dacarbazine on melanoma cells. In mice with transplanted mammary carcinoma, P-carotene enhanced the antitumor effect of cyclophosphamide, and in mice transplanted with Fsall fibrosarcoma or SCC VII carcinoma, p-carotene enhanced the antitumor effect of melphalan, BCNU, doxorubicin, and etoposide. p-Carotene (5 to 50 mg/kg) has been shown to reduce the genotoxicity of cyclophosphamide in mice and of mitomycin C, methyl methanesulfonate, and bleomycin in cultured cells. P-Carotene also reduced the rate of tumor induction in animals receiving chronic low doses of cyclophosphamide. 

Carcinoma of cervix Radiation plus cisplatin (localized), cisplatin, carboplatin (metastatic) Lomustine, cyclophosphamide, doxorubicin, methotrexate, mitomycin, bleomycin, vincristine, interferon, 13-cA-retinoic acid... 

Carcinoma of ovary Cisplatin or carboplatin plus paclitaxel Cyclophosphamide, doxorubicin, melphalan, fluorouracil, vincristine, altretamine, bleomycin... 

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