Phase II trial of perillyl alcohol in patients with metastatic colorectal cancer

Purpose. This is a phase 11 study of perillyl alcohol in the treatment of patients with metastatic colorectal carcinoma. The primary endpoint is time to progression. Secondary objectives are to evaluate objective response rate and toxicity. Patients and Methods. Eligible patients had metastatic adenocarcinoma of the colon or rectum. Patients received perillyl alcohol orally at a dose of 1200 mg/m(2). Dose escalation to 1,600mg/m(2) was allowed. Results. Twenty-seven patients were enrolled. The median time to progression was 1.8 months (range I to 3 mo). Four patients received less than one cycle and were not evaluable for response. Of the remaining 23, all had progressive disease. There were no complete or partial responses. Toxicity was relatively mild, with fatigue, nausea and anemia predominating. Three patients withdrew from therapy for toxicity (grade 3 belching, bloating; grade 2 nausea, fatigue, vomiting, anorexia and increase perspiration; grade I anorexia). Discussion. Despite preclinical evidence of anticancer activity, oral perillyl alcohol administered at this dose and formulation does not appear to have clinical antitumor activity when used for patients with advanced colorectal carcinoma.