Chemotherapy bleomycin

J.S. Lazo. Bleomycin. In Cancer Chemotherapy and Biological Response Modifiers Vol 18, H.M. Pinedo, D.L. Longo, B.A. Chabner (Eds). Elsevier New York,... 

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. 

Bleomycin (BLM) was first isolated as a copper complex from a culture of Streptomyces verticillus. Since then numerous analogs have been prepared by modifying the conditions of fermentation. Bleomycins (114, bleomycin A2) are used clinically in combination cancer chemotherapy for the treatment of head and neck cancer, certain lymphomas, and testicular cancer (555). 

The current was applied in the form of electrical pulses in order to permeabilize the membranes of the tumor cells for the entry of the chemotherapeutic agent bleomycin which is a very potent cytotoxic molecule. Clinical complete responses were achieved in 56.4% of the tumors and partial responses were observed in 28.9% of the tumors. This work is thus not strictly electrochemical treatment in the sense of Nordenstrom18 and Xin32 but is rather chemotherapy aided by electrochemical-driven movement of ions, molecules and drugs etc. (e.g., by electroosmosis, electrophoresis) into the tissue regions targeted for necrosis, as in several studies28,51,93 94 described earlier within this chapter. 

The Northern California Oncology Group randomized 104 patients with unresectable disease to standard daily radiation therapy with or without concomitant bleomycin (5-FU iv twice weekly) followed by 16 wks of adjuvant chemotherapy (methotrexate 25 mg/m2 weekly) after the completion of radiation therapy (22). A locoregional CR of 67% was seen in the concomitant arm vs 45% in the control arm (p = 0.056). The 2-yr locoregional control rate was 64% vs 26% (p = 0.001) and the development of metastases was 38% vs 24% (p > 0.25), respectively. 

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). 

Fu KK, Phillips TL, Silverberg IJ, et al. Combined radiotherapy and chemotherapy with bleomycin and methotrexate for advanced inoperable head and neck cancer update of a Northern California Oncology Group randomized trial. J Clin Oncol 1987 5 1410-1418. 

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. 

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%. 

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. 

Screening of microbial products has led to the discovery of a number of growth-inhibiting compounds that have proved to be clinically useful in cancer chemotherapy. Many of these antibiotics bind to DNA through intercalation between specific bases and block the synthesis of RNA, DNA, or both cause DNA strand scission and interfere with cell replication. All of the anticancer antibiotics now being used in clinical practice are products of various strains of the soil microbe Streptomyces. These include the anthracyclines, bleomycin, and mitomycin. 

Among these are intercalating agents such as dauno-mycin (Figs. 5-22, 5-23), neocarzinostatin, and bleomycin (Box 5-B). These are alkylating reagents800 or attack DNA in other ways. The fact that such compounds are in use for chemotherapy emphasizes the need for new approaches to cancer treatment. 

Another area in which natural products have had a major impact on longevity and quality of life is in the chemotherapy of cancer (see Chapter 62). In fact, most major anticancer drugs are derived from plants or microorganisms. Important examples include bleomycin, doxorubicin, daunorubicin, vincristine, vinblastine, mitomycin, streptozocin, and most recently, paclitaxel... 

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... 

Hodgkin s disease (stages III and IV) Combination chemotherapy vinblastine, doxorubicin, dacarbazine, bleomycin Lomustine, etoposide, ifosfamide, interferon, mechlorethamine, vincristine, procarbazine, prednisone... 

Non-Hodgkin s lymphoma Combination chemotherapy cyclophosphamide, doxorubicin, vincristine, prednisone Bleomycin, lomustine, carmustine, etoposide, interferon, mitoxantrone, ifosfamide, rituximab... 

Carcinoma of testis Combination chemotherapy cisplatin, bleomycin, and etoposide Methotrexate, dactinomycin, plicamycin, vinblastine, doxorubicin, cyclophosphamide, etoposide, ifosfamide plus mesna1... 

De Wit R, Roberts )T, Wilkinson PM et al. (2001) Equivalence of three or four cycles of bleomycin, etoposide and cisplatin chemotherapy and of a 3- or 5-day schedule in good prognosis germ cell cancer a randomised study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cooperative Group and the Medical Research Council. Journal of Clinical Oncology 19 1629-1640. 

The bleomycin assay has been applied to assess the levels of available, nontransferrin-bound iron in plasma samples in patients with iron overload disease (Peters et al., 1985), with acute leukaemia before and after drug chemotherapy (Halliwell et al., 1988), as well as patients with rheumatoid arthritis (Winyard et al., 1987). 

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