Squamous cell carcinoma, bleomycin

Studies on the mechanism of antitumor elfect of bleomycin on squamous cell carcinoma, H. Umezawa, T. Takeuchi, S. Hori, T. Sawa, M. Ishizuka, T. Ichikawa, and T. Komai, J. Antibiot., 25 (1972) 409-420. 

The use of weekly paclitaxel (45 mg/m2) and carboplatin (100 mg/m2) has been reported (135,136). This combination as used to treat 62 patients with stage III and IV squamous cell carcinoma of the head and neck concurrently with radical radiotherapy lead to a clinical complete response rate of 75 % both at the primary and in the neck with a median survival of 33 mo (135). The authors report a retrospective comparison to similar patients treated with concurrent carboplatin alone or concurrent carboplatin and bleomycin and show on multivariate analysis that complete response and treatment with paclitaxel were predictive for survival (136). This result while encouraging is retrospective in nature and is subject to potential bias. 

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

Scheistroen M, Trope C. Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva. Acta Oncol 1992 32 657-661. 

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. 

Bleomycin (Blenoxane) causes chain scission and fragmentation of DNA. With the exception of the skin and lungs, most tissues can enzymatically inactivate bleomycin. Bleomycin is used in the management of squamous cell carcinoma of the head, neck, and esophagus in combination with other drugs in patients with testicular carcinoma, and in the treatment of Hodgkin s disease and other lymphomas. Bleomycin causes stomatitis, ulceration, hyperpigmentation, erythema, and pulmonary fibrosis. 

Bleomycin is used to treat squamous cell carcinoma. 

Systemic vinblastine (velban, others) is approved for use in Kaposi s sarcoma and advanced cutaneous T-cell lymphoma. Intralesional vinblastine also is used to treat Kaposi s sarcoma. Intrale-sional bleomycin (blenoxane, others) is used for recalcitrant warts and has cytotoxic and proin-flammatory effects. Intralesional injection of bleomycin into the digits has been associated with a vasospastic response that mimics Raynaud s phenomenon, local skin necrosis, and flagellate hyperpigmentation. Intralesional bleomycin has been used for palliative treatment of squamous cell carcinoma. Systemic bleomycin has been used for Kaposi s sarcoma (see Chapter 51 for a more complete discussion of these agents). Liposomal anthracyclines [specifically doxorubicin (doxil, CAELYX)] may provide first-line monotherapy for advanced Kaposi s sarcoma. 

Conversely, tumors that are poor in bleomycin hydrase (e.g., squamous cell carcinoma) respond well to this agent. 

Bleomycins glycopeptide antibiotics produced by Streptomyces verticillus and used widely for treatment of squamous cell carcinomas, lymphomas and testicular cancer. About 200 different B. are known, differing mostly in the nature of the C-terminal substituent, which can be varied by adding difierent amines to the bacterial culture medium. The clinically used preparation is a mixture of 11 B., known by the trade name Blenoxane the chief constituents are B.A2 (60-70%) and B.B (20-25%) (Fig.). 

Thatcher et al. (1980) combined weekly intramuscular injections of retinol with adriamycin, bleomycin, S-fluorouracil, and methotrexate for the treatment of 25 patients with advanced squamous cell carcinoma of the head and neck. No effect on response rate or duration by the addition of vitamin A can be determined however, the authors state diat the addition of retinol may have ameliorated drug-induced mucositis. 

Bleomycins are a family of structurally related compounds produced by Streptomyces verticillus (Umezawa et al. 1966). They act through a peculiar mechanism, causing nicks in DNA strands by a complex reaction involving oxygen and metals. A mixture of bleomycins A2 and B2 was introduced in clinics in 1966 for the treatment of squamous cell carcinomas and malignant lymphomas and is still used, mainly in combinations. 

Bleomycins - Complete structures of the bleomycins have not been elucidated. Bleomycin A2 is active against the ascites type of Ehrlich carcinoma and sarcoma 180 in mice, and is clinically useful in the treatment of human epidermoid cancer, squamous cell carcinoma of the head and neck, l3miphosarcoma, Hodgkin s disease, mycosis funoides, Kaposi s sarcoma, carcinoma of the thyroid, and brain tumors.H2-114 it exhibits very... 

Despite the lack of haematological complications associated with the use of bleomycin, alternative toxicities are undoubtedly sigirificant. At the present time bleomycin appears to have some place in the management of a variety of tumours, but predominantly the lymphomas and squamous cell carcinomas. The optimum route and mode of administration has yet to be determined, but the lack of myelotoxicity has encouraged its use in combination with other agents with significant myelotoxicity in the... 

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. 

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