Modified FOLFOX6 with oxaliplatin stop-and-go strategy and oral S-1 maintenance therapy in advanced colorectal cancer: CCOG-0704 study.

Abstract

BACKGROUND:

A combination of fluorouracil and leucovorin (5-FU/LV) with oxaliplatin (FOLFOX) is an established first-line therapy for metastatic colorectal cancer (mCRC). However, the cumulative neurotoxicity of oxaliplatin often requires therapy to be discontinued while the patient is still responding. A strategy to stop FOLFOX, deliver 5-FU/LV as a maintenance therapy and reintroduce FOLFOX was found to be equivalent in terms of efficacy while neurotoxicity was substantially reduced. The aim of this study was to evaluate feasibility of a stop-and-go strategy with S-1, an oral fluoropyrimidine derivative, as a maintenance therapy administered between modified FOLFOX6 (mFOLFOX6) as a first-line treatment of mCRC.

METHODS:

Thirty patients with untreated mCRC were treated with six cycles of mFOLFOX6 followed by maintenance therapy with oral S-1. Reintroduction of mFOLFOX6 was scheduled after four cycles of S-1 or upon tumor progression. The primary endpoint was duration of disease control (DDC).

RESULTS:

Twenty-one of the 30 patients who achieved responses or stabilizations received S-1 maintenance therapy. mFOLFOX6 was reintroduced in 15 patients. Median DDC and progression-free survival were 9.3 and 7.9 months, respectively. The response rates and disease control rates were 40.0 and 86.6% for the initial mFOLFOX6, 23.8 and 57.1% for S-1 maintenance therapy and 20.0 and 73.3% for mFOLFOX6 reintroduction, respectively. Twenty-eight patients (93.3%) had peripheral neuropathy, but grade 3 neurotoxicity was observed in only 1 patient (3.3%).

CONCLUSION:

The planned oxaliplatin stop-and-go strategy with oral S-1 maintenance therapy was feasible as a first-line treatment for Japanese mCRC patients. Further prospective randomized control study is warranted.

• Authors: Goro Nakayama, Yasuhiro Kodera, Hiroyuki Yokoyama, Naoto Okuda, Takuya Watanabe, Chie Tanaka, Naoki Iwata, Norifumi Ohashi, Masahiko Koike, Michitaka Fujiwara, Akimasa Nakao
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 16 Issue 5 Pg. 506-11 (Oct 2011) ISSN: 1437-7772 [Electronic] Japan
• PMID: 21431344 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Drug Combinations
• Organoplatinum Compounds
• Oxaliplatin
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Leucovorin
• Fluorouracil

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Colorectal Neoplasms (drug therapy, pathology)
• Disease-Free Survival
• Drug Combinations
• Female
• Fluorouracil (adverse effects, therapeutic use)
• Humans
• Leucovorin (adverse effects, therapeutic use)
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Organoplatinum Compounds (adverse effects, therapeutic use)
• Oxaliplatin
• Oxonic Acid (administration & dosage, adverse effects, therapeutic use)
• Tegafur (administration & dosage, adverse effects, therapeutic use)