Seminars in oncology
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Seminars in oncology · Dec 2004
ReviewRecent updates in the clinical use of platinum compounds for the treatment of lung, breast, and genitourinary tumors and myeloma.
Platinum compounds have shown activity in a broad spectrum of human tumors in vitro and in vivo. The clinical utility of platinum agents in gynecologic and gastrointestinal cancers (particularly oxaliplatin in colorectal cancer) has been well documented and platinum agents continue to be evaluated in a variety of other cancers. Given preclinical evidence of synergy among some platinum compounds and new anticancer agents, clinical trials exploring platinum-based combination therapies may yield improved treatment for a variety of malignancies. Recent clinical data on new chemotherapeutic strategies for the treatment of lung, breast, and genitourinary cancers and myeloma will be presented in this review.
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Seminars in oncology · Dec 2004
Review Multicenter Study Clinical TrialOpen label multicenter trial of subcutaneous amifostine (Ethyol) in the prevention of radiation induced esophagitis and pneumonitis in patients with measurable, unresectable non-small cell lung cancer.
While concurrent delivery of chemotherapy and radiotherapy (RT) has a synergistic effect on tumor control and improves the median and overall survival in patients with locally advanced non-small cell lung cancer, appreciable acute and late morbidity occur to the esophagus and the lung during treatment (ie, acute radiation esophagitis, pulmonary toxicity). Emerging evidence suggests that the volume of normal lung exposed to certain threshold doses of RT might predict for the incidence of pneumonitis. Clinical data also indicate that amifostine (Ethyol; Medimmune Inc, Gaithersburg, MD), an organic thiophosphate, acts as a selective cytoprotective agent for normal tissues against the toxicities of chemotherapy and RT. ⋯ We are conducting an open-label trial that is accruing patients with locally advanced non-small cell lung cancer, who will receive concurrent chemoradiotherapy (cisplatin/etoposide or carboplatin/paclitaxel plus RT delivered using 3-dimensional conformal radiotherapy treatment planning) and amifostine 500 mg before RT. Incidence and severity of acute radiation esophagitis, acute radiation pneumonitis, chronic radiation pneumonitis, and changes in pulmonary function will be recorded, as will elements of the RT treatment planning (eg, dose volume histogram data for the lung and esophagus). Pre- and post-therapy pulmonary function is a primary endpoint, and others include general safety assessments of subcutaneous amifostine administration.
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Seminars in oncology · Dec 2004
ReviewPreclinical perspectives on the use of platinum compounds in cancer chemotherapy.
Although platinum compounds have long been used in cancer chemotherapy, understanding the biochemistry and specific activity of these agents remains a focus of ongoing research, particularly with regard to next-generation platinum agents. This review will examine current knowledge and recent studies of the molecular mechanisms of platinum DNA damage and repair, including novel platinum DNA targets. Gene expression associated with platinum DNA damage will also be explored, as well as mechanisms of platinum-drug delivery, drug resistance, and future directions in the development of novel platinum agents.