Sequential interferon-α2b, interleukin-2 and fotemustine for patients with metastatic melanoma

Abstract

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.

Treatment of disseminated ocular melanoma with sequential fotemustine, interferon α, and interleukin 2

“…Moreover, metastases from human uveal melanoma express both MHC class I as well as a variety of melanoma associated antigens, and cell lines established from metastatic lesions are excellent targets for lysis by tumour-specific CTL in vitro (Blom et al, 1997b;Sutmuller et al, 2000). This is in accordance with the fact that several -though still preliminary -clinical reports indicate a therapeutic effect of different immune stimulatory approaches (Dorval et al, 1992;Terheyden et al, 2000;Woll et al, 1999;Nathan et al, 1997).…”

“…Thus, metastatic uveal melanoma is still considered to be an incurable disease, with complete responses being only anecdotal (Woll et al, 1999;Pyrhonen, 1998). To this end, the most data gained in prospectively designed clinical trials are available for the nitrosurea fotemustine (Leyvraz et al, 1997;Salmon et al, 1998;Terheyden et al, 1998Terheyden et al, , 2000Jackel et al, 2001).…”

“…This spillover may explain the low incidence of subsequent extrahepatic disease manifestations despite the long course of the disease, suggesting the systemic activity of fotemustine. Data on systemic fotemustine in uveal melanoma, however, are scarce (Terheyden et al, 1998(Terheyden et al, , 2000. If indeed active, systemic fotemustine would be more convenient to administer with the lack of side effects associated with intraarterial hepatic catheters like thrombosis and infection.…”

Therapeutic Cancer Vaccination with Ex Vivo RNA-Transfected Dendritic Cells—An Update

“…Like gemcitabine, fotemustine has already been tested in combination with prolonged vaccination with promising results and no added toxicity [145]. Interestingly, the combination with other immunostimulatory agents, namely IFN alpha + IL-2 and anti-CTL-A4 ICB, was also promising and clinical activity was observed again without evidence for enhanced side effects [146,147].…”