Cisplatin with vinblastine

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. 

Therapeutic applications Cisplatin has found wide application in the treatment of solid tumors such as metastatic testicular carcinoma in combination with vinblastine (see p. 390) and bleomycin (see p. 386), ovarian carcinoma in combination with cyclophosphamide (see p. 388), or alone for bladder carcinoma. Carboplatin is employed when patients cannot be vigorously hydrated as is required for cisplatin treatment, or if they suffer from kidney dysfunction or are prone to neuro- or ototoxicity. 

In a phase III trial in 190 patients with metastatic melanoma, sequential chemotherapy with dacarbazine, cisplatin, and vinblastine plus interferon alfa and aldesleukin modestly increased the response rates and produced considerably more frequent and severe adverse effects than chemotherapy alone (128). In particular, severe episodes of anemia and thrombocytopenia that required blood or platelet transfusions were 2-6 times more frequent in the chemotherapy group. 

Forty patients with lung cancer, treated with a combination of cisplatin, mitomycin, vinblastine, doxorubicin, cyclosphosphamide, and methotrexate, had a significant post-treatment increase in fibrinopeptide A and a fall in fibrinolytic activity, reflected by a fall in functional tissue activator this appeared to be cumulative, depending on the extent of drug exposure (184). 

Samuels BL, Vogelzang NJ, Kennedy BJ. Severe vascular toxicity associated with vinblastine, bleomycin, and cisplatin chemotherapy. Cancer Chemother Pharmacol 1987 19(3) 253-6. 

Bleomycin is highly effective against germ cell tumors of the testis and ovary. In testicular cancer it is curative when used with cisplatin and vinblastine or cisplatin and etoposide. It is used as a component of the standard ABVD regimen for Hodgkin s disease. Bleomycin also is given intrapleurally (60 U)for malignant pleural effusions. 

In an earlier study, digital ischaemia occurred in 41% of patients treated with cisplatin, bleomycin and vinblastine compared with 21% of patients treated with only cisplatin and vinblastine. ... 

Raynaud s phenomenon is common, occurring in one-third to half of those treated with vinblastine and bleomycin or VBP, and there is evidence that blood vessels are pathologically altered. Cisplatin may contribute to the effect. Analysis of late vascular toxicity after chemotherapy for testicular cancer revealed that the use of VBP carried a higher risk of Raynaud s phenomenon than bleomycin with etoposide and cisplatin (BEP). ... 

Intravenous Chemotherapy. The most effective chemotherapeutic agent for bladder carcinoma is cisplatin with objective responses ranging from 26% to 56%, with complete responses seen in 0%-14%. In a study of 121 patients, MVAC (methotrexate, vinblastine, doxorubicin [Adriamycin] and cisplatin) demonstrated an overall response rate of 72% one half of the responses being complete (Sternberg et al. 1989). The median survival was 13 months. CISCA (cisplatin, doxorubicin, and cyclophosphamide) was compared to MVAC MVAC proved to be superior with a difference in median survival of 82 versus 40 weeks (Logothetis... 

Morrell LE, Lee YJ, Hurley J, et al. A Phase II trial of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin in the treatment of patients with locally advanced breast carcinoma. Cancer 1998 82 503-511. 

Loehrer PJ, Einhom LH, Elson PJ, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma a cooperative group study. J Clin Oncol 1992 7 1066-1073. 

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. 

Legha, S.S., S. Ring, O. Eton, A. Bedikian, A.C. Buzaid, C. Plager, and N. Papadopon-los. Development of a biochemotherapy regimen with concurrent administration of cisplatin, vinblastine, dacarbazine, interferon alfa, and interleukin-2 for patients with metastatic melanoma. J Chn Oncol, 1998.16(5) 1752-9. 

Bleomycin is a cytostatic drug that causes double-strand breaks in DNA. It has been used to treat Hodgkin s disease and a variety of solid cancers. It is often used in combination with other anticancer drugs, for example in the regimens known as ABVD (doxorubicin -r bleomycin -r vinblastine-r dacarbazine) and BEP (bleomycin-r etoposide -r cisplatin). It has also been injected intrapleu-rally in the management of malignant effusions. 

Conti JA, Scher HI. Acute arterial thrombosis after escalated-dose methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy with recombinant granulocyte colony-stimulating factor. A possible new recombinant granulocyte colony-stimulating factor toxicity. Cancer 1992 70(ll) 2699-702. 

There have been 21 reports of life-threatening disease affecting large arteries in patients treated with cisplatin, bleomycin, and vinblastine in combination for germ cell tnmors (50,51). Five patients died during or after therapy, three from acnte myocardial infarction, one from rectal infarction, and one from cerebral infarction. Other patients who developed major vascular disease, including coronary artery and cerebrovascnlar disease, have been reported. Symptoms occnrred acntely in some (within 48 honrs of starting therapy), and after months or years had elapsed in others. 

Rednced peripheral circnlation, Raynaud s phenomenon, and polynenropathy have been described after the combined nse of cisplatin, bleomycin, and vinblastine for testicnlar tnmors. Of eight cases with polyneuropathy that were investigated, it was not possible to confirm a cansa-tive association between Rajmand s phenomenon and the chemotherapy (52). 

Vogelzang NJ, Torkelson JL, Kennedy BJ. Hypomagnesemia, renal dysfunction, and Raynaud s phenomenon in patients treated with cisplatin, vinblastine, and bleomycin. Cancer 1985 56(12) 2765-70. 

Hoelzer KL, Harrison BR, Luedke SW, Luedke DW. Vinblastine-associated pulmonary toxicity in patients receiving combination therapy with mitomycin and cisplatin. Drug Intell Clin Pharm 1986 20(4) 287-9. 

TR is a 24-year-old man with testicular cancer who is about to receive a combination of cisplatin, etoposide, and vinblastine. Which factor(s) should be considered prior to administration of the vinblastine ... 

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