OBJECTIVE Tomudex (ZD1694; Zeneca Ltd, Macclesfield, United Kingdom) appears to have a favorable toxicity profile (defined in phase I studies) and antitumor activity in a broad range of epithelial tumors. We report here the results of a large phase II study of Tomudex in advanced colorectal cancer (CRC). METHODS One hundred seventy-seven patients were entered onto the study between October 1992 and September 1993. Patients were required to have advanced CRC without prior chemotherapy (adjuvant chemotherapy was permissible) and at least one measurable lesion. Tomudex (ZD1694) was administered at a dose of 3 mg/m2 intravenously once every 3 weeks in the absence of toxicity or disease progression. Patients were assessed for objective response, progression, and survival. RESULTS Of 177 patients entered onto the study, 5% had received prior adjuvant chemotherapy and 83% had liver metastases. Objective responses were seen in 26% of patients (95% confidence interval, 19% to 33%; four complete responses [CRs] and 41 partial responses [PRs]) while median time to progression was 4.2 months and median survival 9.6 months. All sites were audited, and responses were reviewed by an independent panel. Common toxicities included mild reversible transaminitis, nausea and vomiting, and asthenia or flu-like symptoms, and World Health Organization (WHO) grade 3 and 4 leukopenia and diarrhea were seen in 6% and 9.8% of patients, respectively. Stomatitis and alopecia were common. CONCLUSIONS In this large multicenter phase II study of patients with advanced CRC, interesting activity was seen (objective response rate, 26%). In addition, Tomudex has an acceptable toxicity profile and a convenient dosing schedule (single intravenous injection every 3 weeks) and thus appears to offer real potential as a novel agent for the treatment of patients with advanced CRC.