A Phase II Study of Third-Line Combination Chemotherapy with Bevacizumab Plus S-1 for Metastatic Colorectal Cancer with Mutated KRAS (SAVIOR Study).

Abstract

OBJECTIVE:

No salvage treatment had been established for metastatic colorectal cancer (mCRC) with mutated KRAS before the emergence of the new drugs regorafenib and TAS-102. We performed a phase II study of third-line chemotherapy with combined bevacizumab and S-1 for mCRC.

METHODS:

Subjects were mCRC patients with mutated KRAS who showed disease aggravation even after two regimens with oxaliplatin and irinotecan. Bevacizumab was given intravenously every 2 weeks, and S-1 was administered orally on days 1-28 of a 42-day cycle. The primary endpoint was disease control rate (DCR).

RESULTS:

In total, 31 subjects were enrolled between August 2009 and June 2011. Three subjects in whom antitumor effects could not be evaluated were excluded. The median follow-up period was 8.6 months. The DCR was 67.9%, the response rate 0%, median progression-free survival 3.7 months, and overall survival 8.6 months. In 30 subjects evaluated for safety, there was no treatment-related death. The most common adverse events were anorexia (grade ≥3, 20%), diarrhea (grade 3, 10%), and decreased hemoglobin (grade ≥3, 17%).

CONCLUSIONS:

The results suggest that third-line chemotherapy with combined bevacizumab and S-1 is safe and may delay the progression of mCRC resistant to oxaliplatin and irinotecan with mutated KRAS.

• Authors: Motoki Yoshida, Akinori Takagane, Yasuhiro Miyake, Ken Shimada, Naoki Nagata, Atsushi Sato, Yutaka Ogata, Mutsumi Fukunaga, Koki Otsuka, Takao Takahashi, Hidetomo Matsumoto, Tatsuo Kagimura, Akihito Tsuji
• Journal: Oncology (Oncology) Vol. 91 Issue 1 Pg. 24-30 ( 2016) ISSN: 1423-0232 [Electronic] Switzerland
• PMID: 27229742 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: © 2016 The Author(s) Published by S. Karger AG, Basel.

Chemical References

• Drug Combinations
• KRAS protein, human
• S 1 (combination)
• Tegafur
• Bevacizumab
• Oxonic Acid
• Proto-Oncogene Proteins p21(ras)

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Bevacizumab (administration & dosage, adverse effects)
• Colorectal Neoplasms (drug therapy, enzymology, genetics, pathology)
• Drug Combinations
• Female
• Humans
• Male
• Middle Aged
• Mutation
• Neoplasm Metastasis
• Oxonic Acid (administration & dosage, adverse effects)
• Proto-Oncogene Proteins p21(ras) (genetics)
• Salvage Therapy (methods)
• Tegafur (administration & dosage, adverse effects)