Phase II trial of intravenous melphalan in advanced colorectal carcinoma

Abstract

Background: Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a phase II study to determine the efficacy of administering intravenous melphalan at doses that do not require BMT support in patients with advanced colorectal adenocarcinoma.

Patients and methods: Fifteen patients with histologically proven, bidimensionally measurable disease were treated. The starting dose of melphalan was 30 mg/m2, with dose escalation permitted.

Results: No objective responses were observed. Toxic effects were primarily reversible granulocytopenia and thrombocytopenia. There were no treatment-associated deaths.

Conclusion: Melphalan's lack of efficacy at the doses administered does not disprove the steep chemotherapy dose-response relationship postulated for many solid tumors. However, we feel that it is unlikely that repetitive courses of high dose melphalan with autologous BMT support will be a practical approach to the management of advanced colorectal adenocarcinoma.