Patients with metastatic breast cancer (MBC) are often treated with multiple regimens, and viable options may soon be exhausted. Irinotecan (CPT-11), a topoisomerase 1 inhibitor, is rarely used in this setting, however. Approved for advanced breast cancer in Japan, S-1 is a pyrimidine derivative comprising the combination of tegafur, gimeracil and oteracil. Irinotecan is combined with S-1 (IRIS) to obtain an additive effect, even in the presence of high thymidylate synthase in breast cancer cells. This combination has also been successfully used for gastro-intestinal malignancies in Japan. Method: This study was divided into two steps: step 1, in which the safety profile of the regimen was determined; and step 2, in which tumor response was evaluated if the safety profile was considered acceptable. Irinotecan was given intravenously at a dose of 80 mg/m2 on days 1 and 8 and S-1 orally at 80-120 mg/day depending on body surface area for 2 weeks. The cycle was repeated every 3 weeks.

Results: A total of 21 patients were registered in the study. Median age was 50 years (range, 26 -69 years). Performance status was 0 and 1 in 20 and 1 patients, respectively. Six patients were enrolled in step 1. Grade (G) 3 fatigue and vomiting were observed in 1 patients, G 3-4 neutropenia in 4 and G 3 anemia in 1. The toxicity profile in step 1 was determined acceptable to move on to step 2. Step 2 included 15 patients treated with IRIS. Grade 3-4 neutropenia occurred in 7 out of these 15 patients, fatigue in 1, diarrhea in 3 and anorexia in 1. All patients had previously received anthracyclines and taxanes. Eighteen patients, including 3 patients in step 1, were evaluable for response. A partial response was obtained in 5 patients (27.8%), including in 1 patient who had a history of 4 previous treatments. Progression-free survival in these patients was 137+, 147, 168+, 304+ and 364+ days; no progressive disease was observed in 4 of them. In addition, stable disease was obtained in 5 patients (27.8%) in whom 2 patients experienced SD for longer than 6 months. Conclusion: These results indicate that the IRIS regimen has an acceptable safety profile and modest activity against breast cancer in patients who have been heavily treated with chemotherapy for MBC. We believe the patients responded to the IRIS regimen because irinotecan has a different mechanism of action as compared to other drugs commonly used for breast cancer and complete cross-resistance may not exist between S-1 and capecitabine. This regimen is commonly used for gastric or colorectal cancer in Japan and is considered to be highly tolerable. Therefore, we conclude that this regimen has potential as an option to treat advanced and metastatic breast cancer, although attention must be paid to diarrhea, the dose-limiting toxicity of irinotecan and S-1.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-09.