The impact of dose/time modification in irinotecan- and oxaliplatin-based chemotherapies on outcomes in metastatic colorectal cancer

• DOI: 10.1007/s00280-014-2416-x
• Publication Date: 2014-02-27T07:02:45Z
• Authors: Goro Nakayama; Chie Tanaka; Keisuke Uehara; Naoki Mashita; Naomi Hayashi; Daisuke Kobayashi; Mitsuro Kanda; Suguru Yamada; Tsutomu Fujii; Hiroyuki Sugimoto; Masahiko Koike; Shuji Nomoto; Michitaka Fujiwara; Yuich Ando; Yasuhiro Kodera
• Keywords: Adult; Male; Dose-Response Relationship, Drug; Organoplatinum Compounds; Leucovorin; Middle Aged; Irinotecan; Survival Analysis; Disease-Free Survival; Drug Administration Schedule; 3. Good health; Oxaliplatin; 03 medical and health sciences; 0302 clinical medicine; Antineoplastic Combined Chemotherapy Protocols; Humans; Camptothecin; Female; Fluorouracil; Neoplasm Metastasis; Colorectal Neoplasms; Aged; Retrospective Studies

This study was designed to evaluate (1) the impact of relative dose intensity (RDI) on tumor response and survival outcomes and (2) the influence of dose reduction and schedule modification on outcomes in patients with metastatic colorectal cancer (mCRC).Pooled datasets from two previous phase II trials of FOLFIRI (CCOG-0502; n = 36) and mFOLFOX6 (CCOG-0704; n = 30) in patients with mCRC were analyzed retrospectively. The RDIs of irinotecan and oxaliplatin were compared to response rate (RR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). To assess the effects of dose reduction and schedule modification, the effects of dose index (DI) and time index (TI) on outcomes were evaluated.The median RDIs of irinotecan in FOLFIRI and oxaliplatin in mFOLFOX6 were 80 and 79 %, respectively. Higher RDI of irinotecan in FOLFIRI was associated with significant improvements in RR (65 vs. 6 %, p < 0.01), DCR (100 vs. 59 %, p < 0.01), PFS (9.9 vs. 5.6 months, p < 0.01) and OS (26.7 vs. 12.9 months, p = 0.01) and was the only independent factor associated with PFS [hazard ratio (HR) 8.48, p < 0.01). Higher RDI of oxaliplatin in FOLFOX was significantly associated with DCR (65 vs. 6 %, p < 0.01), and higher TI of oxaliplatin was the only independent factor associated with PFS (HR 2.74, p = 0.04).RDIs of irinotecan and oxaliplatin affected clinical outcomes. Dose reductions in irinotecan, as indicated by DI, and time delays in oxaliplatin, as indicated by TI, were the only independent prognostic factors predicting PFS in patients receiving FOLFIRI and FOLFOX6, respectively.