D F Moore1, R Pazdur, J L Abbruzzese. 1. Department of Gastrointestinal Oncology and Digestive Diseases, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
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.
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.
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