Association between chemotherapy response and rate of disease progression in disseminated melanoma

Abstract

Summary Fifty-five evaluable patients with disseminated malignant melanoma were treated with the combination of dacarbazine (DTIC) 400 mg i.v. on days 1 to 3 and lomustine (CCNU) 50 to 80 mg m-2 orally on day 1 with intervals of 6 weeks as the first line chemotherapy. Three (5%) patients had complete and 6 (11%) partial response, and 7 (13%) patients had stable disease at least for 3 months. The patients with an objective response (n = 9) survived longer than the rest of the patients if the length of survival was calculated from the start of chemotherapy (P = 0.0006). However, the responding patients also had longer time interval from the diagnosis to the detection of distant metastases (P = 0.05), and survival time from disease progression following DTIC and CCNU therapy (P = 0.005). These findings suggest that patients with an objective response to DTIC-CCNU therapy have melanoma with a slow progression rate, and prolonged survival in such patients may in part result from the less aggressive biological nature of their tumours.Combination chemotherapy has in nonrandomised series been reported to increase survival of the responding patients with metastatic melanoma (Seigler et al., 1980), and based on such results combination chemotherapy has been recommended instead of single-agent therapy despite its greater toxicity in this uniformly fatal disease (Young et al., 1985). Subcutaneous, lymph node, and pulmonary melanoma metastases respond to chemotherapy more often than visceral or osseous ones (Joensuu et al., 1986;Mulder et al., 1989;Thatcher et al., 1989). However, disseminated melanoma with subcutaneous, lymph node, or pulmonary metastases may be associated with less aggressive biological behaviour, and, therefore, the longer survival of the responding patients might not merely result from a favourable response to chemotherapy. However, there are currently little data available in the literature indicating that responding melanoma metastases have a slower progression rate than those that do not respond to chemotherapy.In the present retrospective series of 55 patients treated with the combination of dacarbazine (DTIC) and lomustine (CCNU) the progression rate of melanoma was assessed by calculating the time from the diagnosis to the detection of distant metastases, and the length of survival after disease progression following DTIC-CCNU therapy to death, and these estimates of rate of disease progression were correlated with response to chemotherapy. Materials and methodsSixty patients with histologically diagnosed malignant melanoma with distant metastases were treated with DTIC 400 mg i.v. on days 1 to 3 and with CCNU 50-80 mg m-2 p.o. on day 1 with 6 weeks' intervals in the Department of Radiotherapy and Oncology, Turku University Central Hospital, in 1979 to 1987. Dosage was reduced at some stage of treatment because of side-effects only in nine cases (in three responders and in six nonresponders). Fifty-five patients were evaluable and five nonevaluable for response (two patients refused to continue the...

Interim Results of a Phase II Multicenter Clinical Trial Evaluating the Activity of a Therapeutic Allogeneic Melanoma Vaccine (Theraccine) in the Treatment of Disseminated Malignant Melanoma

“…Unfortunately, the correlation of enhanced survival with objective tumor response or disease stabilization was confounded by the fact that patients with single site metastatic disease were more .likely to experience a clinical response or disease stabilization (Table VII), making it difficult to associate survival trends with tumor response. In a similar observation, it has recently been reported in the literature that those disseminated melanoma patients treated with DTIC-CCNU therapy and achieving acomplete or partial response appeared to live longer than those patients failing to achieve an objective clinical response [20]. It was reported that the time from diagno- tion in the context of active-specific immunotherapy of melanoma.…”