TY - JOUR
T1 - The impact of dose/time modification in irinotecan- and oxaliplatin-based chemotherapies on outcomes in metastatic colorectal cancer
AU - Nakayama, Goro
AU - Tanaka, Chie
AU - Uehara, Keisuke
AU - Mashita, Naoki
AU - Hayashi, Naomi
AU - Kobayashi, Daisuke
AU - Kanda, Mitsuro
AU - Yamada, Suguru
AU - Fujii, Tsutomu
AU - Sugimoto, Hiroyuki
AU - Koike, Masahiko
AU - Nomoto, Shuji
AU - Fujiwara, Michitaka
AU - Ando, Yuich
AU - Kodera, Yasuhiro
PY - 2014/4
Y1 - 2014/4
N2 - Purpose: 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). Methods: 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. Results: 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). Conclusion: 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.
AB - Purpose: 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). Methods: 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. Results: 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). Conclusion: 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.
KW - Colorectal cancer
KW - Dose index
KW - Relative dose intensity
KW - Time index
UR - http://www.scopus.com/inward/record.url?scp=84898058105&partnerID=8YFLogxK
U2 - 10.1007/s00280-014-2416-x
DO - 10.1007/s00280-014-2416-x
M3 - 学術論文
C2 - 24577566
AN - SCOPUS:84898058105
SN - 0344-5704
VL - 73
SP - 847
EP - 855
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 4
ER -
