Phase II Study of Ilmofosine in Patients with Malignant Melanoma

Abstract

Background: The thioether phospholipid analogue ilmofosine has demonstrated antineoplastic activity in several experimental tumor systems. In a clinical phase I study tumor response was observed in malignant melanoma, so that a disease-oriented phase II study was started. Material and Methods: 43 patients with advanced and progressive malignant melanoma were treated with the alkyllysophospholipid ilmofosine. Patients with and without pretreatment received 75 mg ilmofosine tablets t.i.d. Response evaluation was performed after an 8-week treatment period. Results: 35 patients were evaluable for response, 15 non-pretreated and 20 pretreated. Disease stabilization was achieved in 11 patients (7 pretreated), 4 had an early progression within the first 8 weeks of treatment and 20 had progressive disease thereafter. In 2 patients a documented tumor progression before study entry was stopped during the treatment period. Gastrointestinal side effects were predominant and dose-limiting. Conclusion: In conclusion, oral ilmofosine has shown limited efficacy in this trial.

Phase II Trial of Orally Administered Miltefosine in Advanced Colorectal Cancer

“…Its exact mechanism of action, although not completely clarified, is related to inhibition of protein kinase C. Due to its high tumor-reductive potential in experimental systems, there was some enthusiasm after the observation of tumor reduction in phase I studies that this new group of cytotoxic drugs could play a significant role in cancer treatment. In the meantime this optimism, due to negative results which were also re ported from other analogues of ether lipids [12][13][14][15], has been replaced by a more sceptical view. Only the topical application of MIL has so far yielded clinically meaningful responses [16].…”