A prospective study of XELIRI plus bevacizumab as a first-line therapy in Japanese patients with unresectable or recurrent colorectal cancer (KSCC1101)

Int J Clin Oncol. 2017 Oct;22(5):913-920. doi: 10.1007/s10147-017-1140-z. Epub 2017 May 19.

Abstract

Background: This study was designed to evaluate the efficacy and toxicity of XELIRI plus bevacizumab for the treatment of Japanese patients with unresectable or recurrent colorectal cancer (CRC).

Methods: This was a multicenter, single-arm, open-label prospective study. The major inclusion criteria were previously untreated unresectable or recurrent CRC, presence of measurable lesions, ≥20 years of age, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients received bevacizumab (7.5 mg/kg on day 1) and XELIRI (irinotecan 200 mg/m2 on day 1 plus capecitabine 800 mg/m2 b.i.d. on days 1-14) every 3 weeks. The primary endpoint was the objective tumor response rate.

Results: A total of 36 patients were enrolled in this study from July 2011 to September 2012. One patient did not fulfill the eligibility criteria and one patient withdrew their consent before the start of the treatment protocol. The confirmed objective response rate was 58.8% (95% CI 35.1-70.2%). The median progression-free survival was 9.6 months (95% CI 5.1-11.1 months) and the median overall survival was 23.1 months (95% CI 11.3-36.7 months). The grade ≥3 adverse events that were frequently encountered in this study were neutropenia (31.4%), leukopenia (22.9%), diarrhea (22.9%), anemia (20.0%), anorexia (20.0%) and febrile neutropenia (17.2%). The frequency of grade 3/4 adverse events, such as neutropenia and leukopenia, was much higher in patients with a UGT1A1 polymorphism.

Conclusions: A first-line therapy comprising XELIRI plus bevacizumab yielded a promising response rate. However, careful attention should be given to adverse clinical events in Japanese patients receiving treatment with unresectable or recurrent CRC.

Keywords: Bevacizumab; Capecitabine; First-line chemotherapy; Irinotecan; Metastatic colorectal cancer; Multicenter single-arm open-label prospective clinical trial.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anorexia / chemically induced
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asian People
  • Bevacizumab / administration & dosage
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Capecitabine / administration & dosage
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Diarrhea / chemically induced
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Glucuronosyltransferase
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neutropenia / chemically induced
  • Prospective Studies
  • Treatment Outcome

Substances

  • Bevacizumab
  • Capecitabine
  • Irinotecan
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Fluorouracil
  • Camptothecin