Phase II study of S-1 plus irinotecan and oxaliplatin for refractory, heavily treated metastatic colorectal cancer

Abstract

15116 Background: Three-drug combination of fluoropyrimidine, irinotecan and oxaliplatin is known to be active for metastatic colorectal cancer (mCRC). In vitro synergy has been reported with each drug, thus combination of all 3-drug may overcome refractoriness to each other. We had performed phase I study to determine doses of phase II study of S-1 plus irinotecan and oxaliplatin (TIROX) for untreated mCRC, favorable responses were also observed in heavily-treated mCRC in phase I. We performed a phase II study of TIROX to evaluate efficacy and safety in refractory, heavily treated mCRC patients (pts) with no further treatment option. Methods: Pts with refractory to all of 3 drugs, age ≥ 18 yrs, PS 0–2, ≥ 1 measurable lesion(s) and adequate organ functions were eligible. S-1 was given 40 mg/m2 twice a day on D1–14, oxaliplatin 85 mg/m2 and irinotecan 150 mg/m2 on D1 every 3 weeks. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression free survival (PFS) and overall survival (OS). Results: Between Mar 2007 and Nov 2007, 19 pts (of 18 planned) were enrolled; median age 50 yrs; M/F 12/7; PS 0/1/2 5/13/1; colon/rectum 11/8. Median OS from initial diagnosis of mCRC to the TIROX was 20.9 months (mo) and G1 sensory neuropathy was noted in 15 pts at baseline. TIROX was their 3rd line regimen in 3 (15.8%), 4th in 13 (57.9%) and ≥ 5th in 3 pts (15.8%). Bevacizumab and cetuximab was exposed previously to 4 and 7 pts, respectively. By intent-to-treat analysis, ORR was 21.1% (95% CI, 8.7 - 43.7) and disease control rate was 52.6% (95% CI 31.5 - 72.8) with 4 PRs and 6 SDs. The median duration of disease control was 4.3 mo (95% CI 1.7–6.9). Median PFS was 2.6 mo (95% CI 2.2 - 2.9) and median OS was not reached with median FU of 7.5 mo. G3/4 toxicities per pt included neutropenia (5, 26.3%), leucopenia (3, 15.8%), febrile neutropenia (2, 10.5%), thrombocytopenia (1, 5.3%), diarrhea (2, 10.5%) and fatigue (2, 10.5%). Conclusions: TIROX seemed to be feasible for refractory, heavily-treated mCRC pts. Combination of previously exposed agents may have activity against refractory mCRC and could be an alternative for pts with good PS but no further treatment options. No significant financial relationships to disclose.