Tamoxifen as a single agent for advanced melanoma in postmenopausal women. A phase II study of the EORTC malignant melanoma cooperative group

Between 1983 and 1989 a phase II study was carried out by the EORTC Malignant Melanoma Cooperative Group in which postmenopausal women with advanced melanoma but a good performance status received tamoxifen, 40 mg per day, as a single agent. From 12 centres, 114 patients were registered of whom 107 appeared to be eligible and 102 evaluable. Seven died of progressive disease within 4 weeks, eight others had early progressive disease (of whom seven died within 7 weeks). The response rate was 4.9%, the complete response rate 1%. Without prior chemotherapy three of 58 responded, with prior chemotherapy two of 44. Except for one of 46 patients with lung metastases who experienced a PR of these metastases, all responders were patients with slowly growing small soft tissue metastases. We conclude that, because of the few side effects, tamoxifen can be recommended for (postmenopausal) patients who have only a small number of slowly growing metastases and who are not yet candidates for treatment with toxic drugs. © 1992 Rapid Communications of Oxford Ltd.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer : The European Organisation for Research and Treatment of Cancer Chronotherapy group

Purpose In two previous randomized trials, the adjustment of chemotherapy delivery to circadian rhythms improved tolerability and anticancer activity compared with constant-rate infusion during 5 days in patients with metastatic colorectal cancer. Patients and Methods For this multicenter randomized trial, it was hypothesized that a chronomodulated infusion of fluorouracil, leucovorin, and oxaliplatin for 4 days (chronoFLO4) would improve survival by 10% compared with conventional 2-day delivery of the same drugs (FOLFOX2). Patients were treated every 2 weeks with intrapatient dose escalation. Results Baseline characteristics were similar in both arms for the 564 patients (36 institutions, 10 countries). Median survival was 19.6 months (95% confidence limit [CL] 18.2, 21.2) with chronoFLO4 and 18.7 months with FOLFOX2 (95% CL = 17.7, 21.0; P = .55). The main dose-limiting toxicities were diarrhea for chronoFLO4 and neutropenia for FOLFOX2. The analysis of survival predictors showed that sex was the single most important factor (P = .001). In women, the risk of an earlier death with chronoFLO4 was increased by 38% compared with FOLFOX2, with median survival times of 16.3 and 19.1 months (P = .03), respectively. In men, the risk of death was decreased by 25% with chronoFLO4 compared with FOLFOX2, with median survival times of 21.4 and 18.3 months (P = .02), respectively. Conclusion Both regimens achieved similar median survival times more than 18 months with an acceptable toxicity. The chronomodulated schedule produced a survival advantage over FOLFOX in men. The strong sex dependency of optimal scheduling of fluorouracil, leucovorin, and oxaliplatin calls for translational investigations of determinants related to the patient's molecular clock

Local treatment of unresectable colorectal liver metastases : results of a randomized phase II trial

Background: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. Methods: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n  38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. Results: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. Conclusions: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases