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01-04-2014 | Original Article

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

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

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2014

Abstract

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.

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Title: The impact of dose/time modification in irinotecan- and oxaliplatin-based chemotherapies on outcomes in metastatic colorectal cancer
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
Publication date: 01-04-2014
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2014
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-014-2416-x

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