Seminars in oncology
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Animal data and clinical trials document the efficacy of amifostine (WR-2721, Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) in decreasing the effects of radiation on normal tissues without decreasing the cytotoxic effects on malignant tumors. The selection of the optimal dose may depend on the intensity of the regimen to be administered as well as on the normal tissues to be protected. Also of important consideration is the question of how to sequence amifostine infusion. ⋯ Although efforts are currently directed at amifostine-mediated modification of acute or late mucosal reactions associated with radiation therapy, there are many other radiation-induced toxicities. Further randomized studies are necessary to document the effects of amifostine on nonmucosal damage. Amifostine has the potential to protect a broad range of normal tissues from the toxicities of radiation and from certain forms of chemotherapy.
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Seminars in oncology · Feb 1999
ReviewA review of the efficacy and safety of docetaxel as monotherapy in metastatic breast cancer.
To date, although statistically significant, the overall impact of adjuvant chemotherapy on the survival of women with nonmetastatic breast cancer has been disappointing. Hence, new agents that have shown good activity against metastatic disease should be assessed quickly in the adjuvant setting. Docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) is one of the most promising drugs that has emerged in recent years, with phase II studies in previously untreated metastatic breast cancer indicating a high overall response rate of approximately 60%. ⋯ The high activity of docetaxel provides a compelling rationale for its study as a component of adjuvant therapies. Investigators in Brussels and Dublin have recently demonstrated the feasibility of two candidate adjuvant programs. Large phase II adjuvant trials involving docetaxel are now being assessed.
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Seminars in oncology · Feb 1999
Randomized Controlled Trial Multicenter Study Clinical TrialA phase III study of irinotecan (CPT-11) versus best supportive care in patients with metastatic colorectal cancer who have failed 5-fluorouracil therapy. V301 Study Group.
In a prospective multicenter trial, 279 patients with metastatic colorectal cancer who had failed 5-fluorouracil therapy were randomized 2:1 to receive either best supportive care (BSC) plus treatment with the topoisomerase I inhibitor, irinotecan (CPT-11; Rhône-Poulenc Rorer, Antony, France), at a dose of 350 mg/m2 every 3 weeks or BSC alone. Overall survival, the primary end point of the study, was significantly improved in patients receiving the irinotecan treatment. Only 14% of patients receiving BSC alone were alive at 1 year compared with 36% in the irinotecan group. ⋯ Appreciable deterioration in global quality of life (50% reduction from baseline) occurred significantly later in the irinotecan-treated patients than in the controls. Additionally, quality of life analyses of all symptoms, except diarrhea, mean scores were significantly in favor of patients assigned to irinotecan treatment than those assigned to BSC. This is the first time that the benefit of second-line chemotherapy has been demonstrated by a randomized controlled trial in advanced colorectal cancer.
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Seminars in oncology · Feb 1999
ReviewIncorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer.
Combined chemotherapy and thoracic radiation therapy has emerged as a primary treatment option for locally advanced, unresectable non-small cell lung cancer (NSCLC). Randomized trials and subsequent metaanalyses have shown a clear survival benefit with platinum-based combination chemotherapy administered sequentially or concurrently with hyperfractionated thoracic radiation over radiation alone. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin recently have been evaluated in numerous phase 1/11 trials at various doses in both sequential and concurrent schedules with thoracic radiation in patients with locally advanced and unresectable NSCLC. ⋯ Numerous phase II and III trials are currently planned or under way to further define the efficacy of this novel combination of paclitaxel/carboplatin in combined-modality programs in an attempt to determine the optimal administration sequence of chemotherapy and thoracic radiation. These combined-modality programs are now being integrated into trials for early stage, potentially resectable disease. Thus, NSCLC is in fact a systemic disease requiring a multidisciplinary approach for optimal management.
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Seminars in oncology · Feb 1999
ReviewComparing irinotecan with best supportive care and infusional 5-fluorouracil: a critical evaluation of the results of two randomized phase III trials.
Two randomized phase III trials have been conducted in colorectal cancer patients with nonbulky metastatic disease who have failed first-line therapy with 5-fluorouracil (5-FU). In one trial, the use of 350 mg/m2 irinotecan was shown to significantly prolong survival relative to best supportive care. Patients receiving irinotecan also experienced higher quality of life than the controls. ⋯ The results of these trials have implications for everyday clinical practice. When appropriate, irinotecan should be offered to patients who have failed 5-FU. Irinotecan should be the reference arm for future studies of investigational second-line drugs; the potential of irinotecan (alone or in combination) in the first-line and adjuvant treatment of colorectal cancer now needs to be evaluated.