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

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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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Conflict of interest

The authors have declared no conflict of interests.

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Authors and Affiliations

  1. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan

    Goro Nakayama, Chie Tanaka, Naoki Mashita, Naomi Hayashi, Daisuke Kobayashi, Mitsuro Kanda, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Masahiko Koike, Shuji Nomoto, Michitaka Fujiwara & Yasuhiro Kodera

  2. Department of Surgical Oncology (Surgery I), Nagoya University Graduate School of Medicine, Nagoya, Japan

    Keisuke Uehara

  3. Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan

    Yuich Ando

Authors
  1. Goro Nakayama
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  2. Chie Tanaka
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  3. Keisuke Uehara
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  4. Naoki Mashita
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  5. Naomi Hayashi
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  7. Mitsuro Kanda
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  8. Suguru Yamada
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  11. Masahiko Koike
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  12. Shuji Nomoto
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  13. Michitaka Fujiwara
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  14. Yuich Ando
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  15. Yasuhiro Kodera
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Corresponding author

Correspondence to Goro Nakayama.

Additional information

Trial registration: These trials, CCOG-0502 Study (A multicenter, single-arm phase II clinical trial to evaluate the efficacy and toxicity of FOLFIRI in metastatic colorectal cancer patients with UGT1A1*28 wild-type gene) and CCOG-0704 Study (A multicenter, single-arm phase II clinical trial to evaluate the efficacy and safety of mFOLFOX6 with oxaliplatin stop-and-go strategy and oral S-1 maintenance therapy in advanced colorectal cancer), were conducted by Chube Clinical Oncology Group (CCOG). CCOG had not registered a trial at the time the current trials were designed (years 2005 and 2006), although we did begin to register all trials by the year 2008.

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Nakayama, G., Tanaka, C., Uehara, K. et al. The impact of dose/time modification in irinotecan- and oxaliplatin-based chemotherapies on outcomes in metastatic colorectal cancer. Cancer Chemother Pharmacol 73, 847–855 (2014). https://doi.org/10.1007/s00280-014-2416-x

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  • DOI: https://doi.org/10.1007/s00280-014-2416-x

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