Fotemustine

Abstract: One hundred sixty-nine patients with histologic evidence of disseminated malignant melanoma, including patients with cerebral metastases, were entered into a Phase II study of the nitrosourea fotemustine. The treatment regimen consisted of a 100 mg/m2 1 hour IV infusion every week for 3 consecutive weeks, followed by a 4- to 5-week rest period (induction therapy). In responding or stabilized patients, maintenance therapy consisted of 100 mg/m2 every 3 weeks until the disease progressed. One hundred fifty-three patients were evaluable for response. Three complete responses and 34 partial responses were observed (according to the World Health Organization criteria), leading to an objective response rate of 24.2% (95% confidence interval: 17.4% to 31.0%). Responses were also documented on cerebral (25.0%), visceral (19.2%), or nonvisceral (31.8%) metastatic sites. The median duration of response was 22 weeks (range, 7 to 80 weeks). The objective response rate in previously untreated patients was 30.7% (19 of 62 patients). The main toxicity was hematologic with delayed and reversible leukopenia and/or thrombopenia. The objective response rate observed (especially in untreated patients), the activity on cerebral metastases, and the small amount of extra-hematologic toxicity encountered suggest that fotemustine is an effective drug in disseminated malignant melanoma.

Abstract: Artesunate (ART) is a derivative of artemisinin, the active principle of the Chinese herb Artemisia annua L Artesunate is approved for the treatment of multidrug-resistant malaria and has an excellent safety profile It has been shown that Artesunate, apart from its anti-malarial activity, has cytotoxic effects on a number of human cancer cell lines, including leukemia, colon cancer and melanoma We report on the first long-term treatment of two cancer patients with ART in combination with standard chemotherapy These patients with metastatic uveal melanoma were treated on a compassionate-use basis, after standard chemotherapy alone was ineffective in stopping tumor growth The therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone One patient experienced a temporary response after the addition of ART to Fotemustine while the disease was progressing under therapy with Fotemustine alone The second patient first experienced a stabilization of the disease after the addition of ART to Dacarbazine, followed by objective regressions of splenic and lung metastases This patient is still alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a median survival of 2-5 months Despite the small number of treated patients, ART might be a promising adjuvant drug for the treatment of melanoma and possibly other tumors in combination with standard chemotherapy Its good tolerability and lack of serious side effects will facilitate prospective randomized trials in the near future

Abstract: The treatment of advanced cutaneous melanoma remains disappointing. Single-agent cytotoxic drugs usually produce response rates of less than 20%, though newer agents, particularly fotemustine and temozolomide, show some promise, especially in patients with brain metastases. Combination chemotherapy regimens yield response rates of 20% to 40%, but durable complete remissions are uncommon. Interferon-alfa and interleukin-2 alone produce response rates of 10% to 20%, 3% to 5% of which are durable. Vaccines and monoclonal antibodies have low level activity in advanced disease but may play a role in the adjuvant setting. The combinations of cisplatin-based regimens plus IFN-alfa and IL-2 have produced overall response rates of 50% to 60% and complete responses in 20% of patients, about half of which are durable. The toxicity of these regimens is severe, however, and their impact on survival remains to be established.