A randomized phase II study of combination therapy with S-1, oral leucovorin, and oxaliplatin (SOL) and mFOLFOX6 in patients with previously untreated metastatic colorectal cancer.

Abstract

PURPOSE:

Biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) enhances antitumor activity. LV is thus often added to 5-FU-based regimens for the treatment of metastatic colorectal cancer (mCRC). A combination of S-1, oxaliplatin, and LV (SOL) was shown to be feasible, effective, and safe in a previous phase I trial. We therefore conducted a randomized phase II trial to evaluate efficacy and safety of SOL compared with mFOLFOX6.

METHODS:

Patients with mCRC and no prior chemotherapy were randomly assigned to receive either SOL or mFOLFOX6. SOL consisted of S-1 (40-60 mg bid) plus oral LV (25 mg bid) for 1 week and oxaliplatin (85 mg/m(2)) on day 1, repeated every 2 weeks.

RESULTS:

Among 107 patients enrolled from July 2008 through July 2009, 105 (56 in the SOL group and 49 in the mFOLFOX6 group) were eligible and evaluated. The median progression-free survival was 9.6 months in the SOL group and 6.9 months in the mFOLFOX6 group [hazard ratio (HR) 0.83, 95 % confidence interval (CI) 0.49-1.40]. The median overall survival was 29.9 and 25.9 months, respectively (HR 0.91, 95 % CI 0.55-1.49). The response rate was 55 % in both groups. Grade 3 or 4 adverse drug reactions were neutropenia (20 % with SOL vs 41 % with mFOLFOX6), sensory neuropathy (20 vs 2.0 %), anorexia (13 vs 7.8 %), fatigue (11 vs 5.9 %), and diarrhea (11 vs 3.9 %).

CONCLUSIONS:

SOL demonstrated promising efficacy and acceptable toxicity as first-line chemotherapy for mCRC. Further studies of SOL combined with molecular target agents are warranted.

• Authors: Kentaro Yamazaki, Hiroyuki Kuwano, Hitoshi Ojima, Toshio Otsuji, Takeshi Kato, Ken Shimada, Ichinosuke Hyodo, Tomohiro Nishina, Kuniaki Shirao, Taito Esaki, Takashi Ohishi, Tadamichi Denda, Masahiro Takeuchi, Narikazu Boku
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 75 Issue 3 Pg. 569-77 (Mar 2015) ISSN: 1432-0843 [Electronic] Germany
• PMID: 25575764 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

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