Bleomycin with vinblastine

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. 

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 Bleomycin is primarily employed in the treatment of testicular tumors in combination with vinblastine (see p. 390) or etoposide (see p. 397). Response rates are close to... 

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. 

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. 

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). 

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

DIC (NSC 45388) is found to be active against mouse leukemia L 1210, sarcoma 180 and adenocarcinoma. BIC was found to be most potent suggesting thereby that halo-substitution are often more potent in antineoplastic activity. At present DIC is mostly employed in malignant malanoma. It is used in combination with adriamycin, bleomycin and vinblastine in the treatment of Hodgkin s diseases and in sarcomas with adriamycin. 

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). ... 

A common method of minimizing the toxicity of antineoplastic agents is to administer them along with a number of other antineoplastic agents at reduced dose levels. Thus, cis-DDP has been administered in combination with adriamycin (ADM), cyclophosphamide (CTX), bleomycin (BLM), vinblastine (VBL) and actinomycin D (ACD), among other agents. 

Unexplained transient hyperbilirubin-aemia was reported (72) in about 30% of patients receiving bleomycin in combination with vinblastine. Bleomycin was given by continuous i.v. infusion over a 14-hour period for S successive days. Hypertension was a new and unexpected side effect experienced by all patients which was sustained and usually noted by day 6 and lasted for several days. One of these patients developed an acute anterior myocardial infarction. 

Samuels, M. L., Johnson, D. E. and Holoye, P. Y. (1975) Continuous intravenous bleomycin (NSC-125066) therapy with vinblastine (NSC-49842) in stage HI testicular neoplasia. Cancer Chemother. Rep., 59, 563. 

Chemotherapeutic agents are grouped by cytotoxic mechanism. The alkylating agents, such as cyclophosphamide [50-18-0] and melphalan [148-82-3] interfere with normal cellular activity by alkylation deoxyribonucleic acid (DNA). Antimetabohtes, interfering with complex metaboHc pathways in the cell, include methotrexate [59-05-2] 5-fluorouracil [51-21-8] and cytosine arabinoside hydrochloride [69-74-9]. Antibiotics such as bleomycin [11056-06-7] and doxombicin [23214-92-8] h.a.ve been used, as have the plant alkaloids vincristine [57-22-7] and vinblastine [865-21-4]. 

MANAGING ALOPECIA. Alopecia (loss of hair) is a common adverse reaction associated with some of the antineoplastic drugs. Some drugs cause severe hair loss, whereas others cause gradual thinning. Examples of drug commonly associated with severe hair loss are doxorubicin and vinblastine Methotrexate, bleomycin, vincristine, and etoposide are associated with gradual hair loss. 

In an attempt to reduce relapse rate and late toxicity, combined-modality therapy using lower doses of radiation and an abbreviated course of chemotherapy has been evaluated.16 The goal of decreased relapse rate has been achieved, but no overall survival benefit has been documented. A limitation of this approach is exposing patients to the additive toxicities of chemotherapy. Trials that have investigated this approach typically have incorporated between two and four cycles of a standard regimen for HL, such as ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with involved-field radiation. At present, combined-modality therapy is considered to be a standard of care for stage I/II HL. 

JM is a 32-year-old woman who was recently diagnosed with stage IIIB Hodgkin s disease. She comes to the clinic to receive her first dose of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy. She currently does not have a central access device therefore, she will receive her chemotherapy via peripheral vein. 

A 34-year-old male with Hodgkin s disease is treated with the adri-amycin, bleomycin, vinblastine, and decarbazine (ABVD) regimen. What is the mechanism of action of vinblastine ... 

Merlano and colleagues completed a phase III study comparing sequential vs alternating chemoradiotherapy (62). One hundred sixteen patients were randomized to arm A of the sequential regimen of four cycles of Vinblastine (6 mg/m2, h 0), bleomycin (30 mg, h 6), methotrexate (200 mg, h 24-26), and leucovorin (45 mg, h 48) followed within 3 wk by definitive radiotherapy or arm B composed of the same chemotherapy regimen alternating with three courses of daily fractionated therapy for 2 wk. The difference in response rates (52% for arm A vs 64.9% for arm B) was found to be statistically significant, p < 0.03, as well as the median PFS (26 vs 34 wk, p = 0.046) without differences seen in OS (p = 0.64). 

Hodgkin s disease accounts for 1% of all new cancers diagnosed in Western countries and for 15% of all malignant lymphomas. In patients with early stage lA-IIA disease without B-symptoms or bulky adenopathy, therapy consists of either extended field radiotherapy or limited duration chemotherapy, e.g. ABVD (anthracycline, bleomycin, vinblastine, dacarbazine) for 3-4 cycles followed by involved field radiotherapy. Radiation alone results in a 10-year relapse free survival of 70-75% and, because of the efficacy of salvage chemotherapy for those who relapse, an overall survival of 80-85%. The combined modality approach results in fewer relapses but overall survival is similar. In order to reduce the long term morbidity of radiation current trials are exploring combined modality treatment with lower radiation doses versus chemotherapy alone. 

The chemotherapy of advanced Hodgkin s disease is one of the best examples of successful combination chemotherapy. Combination therapy with the MOPP regimen (mechlorethamine, Oncovin [vincristine sulfate], procarbazine, prednisone), alternating with ABVD (Adriamycin [doxorubicin hydrochloride], bleomycin, vinblastine, dacarbazine), has resulted in cure rates of 50 to 60%. 

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. 

AR is a 48-year-old woman who was treated for Hodgkin s disease 15 years ago with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). She now presents with breast cancer and her oncologist feels that chemotherapy with FAC (fluorouracil, doxorubicin [Adriamycin], and cyclophosphamide) is the most appropriate regimen. Her previous chemotherapy included a total of 300 mg/m doxorubicin exposure. Which of the following agents may be utilized to reduce risk of cardiotoxicity associated with the anthracycline therapy she is about to receive ... 

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