Sequential interferon-alpha2b, interleukin-2 and fotemustine for patients with metastatic melanoma.

The aim of this study was the evaluation of both the antitumour activity and toxicity of an immunochemotherapeutic regimen consisting of interferon-alpha2b and interleukin-2 in combination with fotemustine for patients with metastatic melanoma. To improve the penetration of fotemustine into the brain, it was given immediately after immunotherapy, when the blood-brain barrier is still disturbed. Of the 19 patients treated, three complete remissions (CRs) and one partial remission (PR) were induced, giving an objective response rate of 21% (95% confidence interval 6-46%). The durations of the CRs were 9, 19 and 44 months; the PR lasted for 59+ months. The overall survival times for the patients with CR were 21, 25 and 70+ months, and 59+ months for the PR. For nine patients (47%, 95% confidence interval 24-71%) disease was stabilized for a median period of 8 months (range 2-18 months), resulting in a median survival of 18 months (range 10-41+ months). No haematological toxicity of World Health Organization grade 3 or more was observed and in general toxicity was low. In summary, this immunochemotherapy regimen led to long-term survival in occasional patients, and about half of the patients achieved stable disease, with prolonged treatment- and progression-free survival compared with nonresponding patients. The occurrence of brain metastases, however, was not prevented, and in fact was the site of recurrence in those patients achieving a CR. Due to its low toxicity, this protocol can be applied at a community hospital level.