37 th Annual Meeting of the American Society of Clinical Oncology; San Francisco, CA May 12–15, 2001

Abstract

5-Fluorouracil (5-FU) is one of the most efficacious agents in colorectal cancer. Capecitabine is an oral 5-FU prodrug that is converted eventually to 5-FU by a series of 3 enzymatic reactions. The final step is catalyzed by thymidine phosphorylase (TP), which is expressed at higher levels within neoplastic cells when compared with normal cells, thus creating a level of specificity of activation for this drug. In addition, capecitabine is administered orally, creating a condition similar to continuous infusion 5-FU. In 2 independent phase III studies in previously untreated patients with advanced colorectal cancer, capecitabine was superior to 5-FU in terms of overall response rate (ORR) (26% versus 17%, P < 0.0002).1,2 The median time to progression and survival were similar for both treatments, but capecitabine had a more favorable toxicity profile, with fewer and less severe treatment-related side effects compared to 5-FU. Given the clinical efficacy of 5-FU and irinotecan in advanced colorectal cancer, it was logical to determine whether capecitabine could be used in combination with irinotecan in place of 5-FU. Dr. Schleucher and colleagues from Germany undertook a phase I trial of capecitabine in combination with irinotecan in patients with advanced colon cancer.3 The results were presented at the 2001 American Society of Clinical Oncology (ASCO) Meeting in San Francisco, California. The inclusion criteria for this study included metastatic colorectal cancer, measurable disease, a World Health Organization (WHO) performance status (PS) of 0-2, no prior chemotherapy or radiation therapy for metastatic disease, and adequate organ function. Patients were treated with escalating doses of capecitabine (1000-1250 mg/m2 b.i.d.) on days 1-14 and 22-36 along with escalating doses of irinotecan (70-90 mg/m2/week) given 6 of every 7 weeks. The dose escalation schema is shown in Table 1. Thirty-seven patients were enrolled. The median age was 60 years (range, 32-71 years), and the median PS was 0 (range, 0-2). Sixteen patients (43%) presented with a primary tumor in the rectum, 22 (59%) presented with a primary tumor within the colon, and 1 patient presented with disease in both the colon and rectum. Fourteen patients had received prior adjuvant treatment with chemotherapy, radiation therapy, or both. 37th Annual Meeting of the American Society of Clinical Oncology San Francisco, CA May 12-15, 2001 Highlights Meeting