Seminars in oncology
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Seminars in oncology · Jun 1999
Clinical TrialDocetaxel (Taxotere) administered in weekly schedules.
The administration of a weekly low-dose taxane markedly reduces the severity of myelosuppression compared with a once-every-3-week schedule and allows the dose intensity (mg/m2/wk) of treatment to be increased. The dose-limiting toxicity observed in a weekly phase I trial was fatigue/asthenia. The maximum tolerated dose of a weekly docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) phase I study was 43 mg/m2; 36 mg/m2 was recommended for further study. ⋯ Other studies have been conducted to evaluate the efficacy and safety of the weekly schedule. One such study is an ongoing phase II trial in elderly or medically unfit patients with previously untreated advanced non-small cell lung cancer in whom weekly docetaxel appears active and well tolerated. Further investigation of weekly docetaxel alone or in combination is warranted.
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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
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
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialIrinotecan versus infusional 5-fluorouracil: a phase III study in metastatic colorectal cancer following failure on first-line 5-fluorouracil. V302 Study Group.
In a multicenter phase III trial, 267 patients with nonbulky metastatic colorectal cancer who had failed first-line 5-fluorouracil (5-FU) therapy were randomized to receive second-line treatment with either the new topoisomerase agent, irinotecan (Rhône-Poulenc Rorer, Antony, France), or a high-dose infusional 5-FU regimen. Patients treated with irinotecan survived significantly longer than those treated with infusional 5-FU. The 1-year survival rate was 45% for patients receiving irinotecan compared with 32% for patients receiving 5-FU. ⋯ Overall, mean global quality of life scores were similar in the two arms of the study throughout the period of treatment and follow-up, demonstrating that the more effective disease control achieved by irinotecan at least maintains quality of life. Indeed, deterioration in quality of life (defined as >50% decrease from baseline score) occurred significantly later in irinotecan-treated patients. In light of these data, irinotecan should be considered the reference treatment for patients with 5-FU-refractory advanced colorectal cancer.
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Seminars in oncology · Feb 1999
ReviewSetting a new standard--irinotecan (Campto) in the second-line therapy of colorectal cancer: final results of two phase III studies and implications for clinical practice.
The final results of two very important randomized trials of irinotecan (Campto, Rhône-Poulenc Rorer, Antony, France) as second-line treatment for patients with advanced colorectal cancer are presented. In one trial, the new topoisomerase inhibitor was compared with best supportive care; in the other, its use was compared with the strategy of high-dose 5-fluorouracil (5-FU) infusion. ⋯ In the comparison with infusional 5-FU, the more effective antitumor activity of irinotecan may have helped maintain quality of life. These results have implications for clinical practice: following failure on 5-FU, irinotecan must now be considered the best available option for treatment.