PHASE-II TRIAL OF ORALLY-ADMINISTERED MILTEFOSINE IN ADVANCED COLORECTAL-CANCER

Background: Treatment results in advanced colorectal cancer (CC) remain unsatisfactory and palliative, with 5-fluorouracil with or without calcium folinate being the only drug able to induce clinically acceptable response rates. Patients and Methods: A clinical phase II study is presented with an oral formulation of the phospholipid derivative miltefosine (MIL) in patients with advanced colorectal cancer. Patients were stratified according to pretreatment. Only non-pretreated or pretreated patients who had received 5-fluorouracil with or without calcium folinate were accepted. MIL was given as capsule twice daily at a single dose of 50 mg for the lst week with dose escalation to 150 mg (50 mg X 3) in the 2nd week and subsequently in case of good tolerability. Nine weeks were considered the minimal duration of treatment. Results: 54 patients were evaluable for toxicity and 44 were evaluable for response. A short-lived partial response was observed in one pretreated female patient with multiple lung lesions, a 'no change' status in 14 patients, including 8 nonpretreated patients (42%) and 6 pretreated patients (24%). Side effects were distinct, with loss of appetite, nausea and vomiting up to grade 4 WHO and weight loss of more than 5 kg in 3 months in a considerable number of patients. Furthermore, an increase of leukocyte and platelet counts was observed during the first 2 months of treatment. Conclusion: Oral MIL is considerably toxic and has only marginal therapeutic activity in patients with colorectal cancer.