Vinblastine bladder cancer

MVAC Methotrexate, vinblastine daunomycin, cyclophosphamide Bladder cancer... 

Roth BJ, Bajorin DF. Advanced bladder cancer the need to identify new agents in the post-M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) world. J Urol 1995 153 894-900. 

Medical Research Council Advanced Bladder Cancer Working Party. Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer a randomised controlled trial. Lancet 1999 354 533-540. 

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. 

Vinblastine is used in combination with other cytotoxic agents for the treatment of disseminated Hodgkin s disease stages III and IV, non-Hodgkin s lymphoma, histiocytic lymphoma, and advanced carcinoma of the testis. It has also been used for the treatment of bladder cancer, melanoma, and renal cell cancer. The usual adult dosage is 3-6 mg/m intravenously for the treatment of testicular germ cell tumors and Hodgkin s disease (1,2). 

It is employed in combination witli vinblastine and bleomycin for the treatment of metastatic testicular tumours. It is also used for the remission of metastaticovarian tumours when given either alone or in combination with doxorubicin. It also exhibits activity against a host of other tumours, such as cervical cancer, neck and head cancer, penile cancer, bladder cancer and small-cell cancer of the lung. 

Soon after clinical impact of these phytochemicals in curative and palliative cancer chemotherapies, a number of studies focused on design of their semisynthetic derivatives were developed. These efforts led to important anticancer agents, including vindesine (21), vinorelbine (22), and vinilunine (23). Vinorelbine has been administered for treating non-smaU ceU lung cancer (NSCLC), metastatic breast cancer, and rhabdomyosarcoma [98], Vindesine is usually used to treat leukemia, lymphoma, melanoma, and breast and lung cancers. Vinflunine is a fluoiinated vinblastine derivative and has been submitted to phase III clinical studies in patients with NSCLC and bladder cancer [99]. 

Vinblastine is another vesicant vinca alkaloid that causes myelo-suppression and less neurotoxicity than vincristine. The pharmacokinetics of vinblastine are best described by a three-compartment model, with an a half-life of 25 minutes, a 3 half-life of 53 minutes, and a terminal half-life of 19 to 25 hours.12 Vinblastine has shown activity in the treatment of bladder, breast, and kidney cancer, as well as some lymphomas. The doses of vinblastine tend to be higher on a milligram per meter squared basis than vincristine. Nausea and vomiting are minimal with vinblastine. Other side effects include mild alopecia, rash, photosensitivity, and stomatitis. 

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. 

An MAA for vinflunine (Javlor ) 43 (Pierre Fabre) has been submitted to the European Medicines Agency (EMEA) for the treatment of various cancers.103 Pierre Fabre had been developing vinflunine 43104 106 in the USA in partnership with Bristol-Myers Squibb for the treatment of breast, bladder and lung cancers but development was halted in late 2007.107 Four Vinca-type alkaloids have been approved for cancer treatment vinblastine 44108 and vincristine... 

EC145 (A5), a folic acid conjugate of desacetyl vinblastine monohydrazide, represents a new generation of receptor-specific targeted chemotherapy and is undergoing Phase I anticancer clinical trials (19). Phase II trials for bladder and kidney cancers are underway with vinflunine (A6), a bifluorinated vinorelbine derivative (20, 21). 

Cisplatin, in combination with bleomycin, etoposide, ifosfamide, or vinblastine, cures 90% of patients with testicular cancer. Used with paclitaxel, cisplatin induces complete response in most patients with carcinoma of the ovary. Cisplatin produces responses in cancers of the bladder, head and neck, cervix, and endometrium all forms of carcinoma of the lung anal and rectal carcinomas and neoplasms of childhood. The drug sensitizes cells to radiation therapy and enhances control of locally advanced lung, esophageal, and head and neck tumors when given with irradiation. 

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