PHASE-II STUDY WITH IODODOXORUBICIN IN MEASURABLE ADVANCED COLORECTALADENOCARCINOMA - EFFECTIVE RESCUE USING WEEKLY HIGH-DOSE 5-FLUOROURACIL (WFU)

Aims and background: To evaluate a new anthracycline 4'-iodo-4'-deoxyd oxorubicin (I-DOX) in patients with measurable advanced colorectal ade nocarcinoma in a phase II study. Methods: We investigated therapeutic activity and toxicities associated with repeated courses of I-DOX 80 m g/m2 administered every 3 weeks. Eighteen patients entered the trial, all of them evaluable for response and toxicity. Results: A total of 4 7 courses were administered. The median cumulative I-DOX dose was 238 mg/m2 (80-320). Myelosuppression, particularly leukopenia, was the mos t frequent and serious side effect associated with I-DOX treatment; Wo rld Health Organization (WHO) grade 3-4 leukopenia occurred in 4 patie nts (22%). No thrombocytopenia was observed except in 1 patient who pr esented WHO grade 4. Only 1 patient developed febrile neutropenia but recovered uneventfully. Overall, the I-DOX treatment was well tolerate d. Grade 3-4 nausea/vomiting was observed in 2% of the cycles and no o ther severe toxicities were recorded.Echocardiography or multiple gate d scan was performed before treatment and during follow-up in 14 patie nts to measure left ventricular ejection fraction (LVEF), and a decrea se >15% was detected in 3, including 1 whose LVEF fell below normal va lues (48%) (normal range >49%). There were no cases of congestive hear t failure or treatment-related deaths. No complete or partial response (PR) was observed. Twelve patients received weekly high-dose 5-fluoro uracil (WFU) as rescue. Four patenties had PR, 5 no change and 3 progr essive disease (PD). The median time to PD of the whole group from stu dy entry to failure after WFU was 30 weeks and the overall median surv ival was 11 months. Conclusions: As reported for other anthracyclines, I-DOX showed no activity in colorectal adenocarcinoma; however, the u se of an investigational agent as front-line chemotherapy for colorect al adenocarcinoma does not compromise further response to 5-FU.