Results of a phase II trial of cetuximab plus capecitabine/irinotecan as first-line therapy for patients with advanced and/or metastatic colorectal cancer

Clin Colorectal Cancer. 2008 Nov;7(6):390-7. doi: 10.3816/CCC.2008.n.052.

Abstract

Background: XELIRI (capecitabine/irinotecan) is effective and well tolerated in metastatic colorectal cancer (mCRC). Cetuximab is active in mCRC alone or with chemotherapy. This study evaluated cetuximab plus XELIRI in first-line treatment of mCRC.

Patients and methods: Subjects had histologically confirmed unresectable colorectal adenocarcinoma (with T4 lesions) after preoperative chemoradiation and/or metastases. Treatment was capecitabine 1700 mg/m2 (850 mg/m2 orally twice a day on days 1-14 for 3 weeks), irinotecan 200 mg/m2 intravenously (I.V.) on day 1 every 3 weeks, and weekly cetuximab (initially 400 mg/m2 I.V. [120 minutes], subsequently 250 mg/m2 [30 minutes]).

Results: Baseline characteristics (N = 70): 43 men (61%); median age, 61.5 years; Eastern Cooperative Oncology Group performance status 0/1 = 66%/34%; 94% adenocarcinoma. Previous therapy: surgery (91%), chemotherapy (14%), or radiation therapy (7%). Responses (patients completing > or = 2 cycles): complete response (5.7%), partial response (37.7%), stable disease (43.4%), and progressive disease (PD; 13.2%); 16 patients discontinued early (n = 4 allergic reaction, n = 2 withdrew consent, n = 2 death, and n = 8 other adverse events [AEs]). The overall per-protocol response rate was 43.4% (34% intent to treat [ITT]; disease control rate, 86.8%; 69% ITT). The median time to progression was 8.1 months (range, < 1-27.0 months), and the median time to response was 1.6 months (range, 1.1-8.4 months). The median survival was 20.5 months, and 45.7% of patients remain alive. Of the 38 deaths, 84% were because of PD. No death was treatment related. The most frequent grade 3/4 treatment-related AEs included diarrhea, neutropenia, and nausea/vomiting; 32% of patients required dose reductions. All patients are off the study primarily because of PD (34.3%) or AEs (40.0%).

Conclusion: In summary, XELIRI plus cetuximab is a promising regimen that merits further study for first-line mCRC.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Capecitabine
  • Cetuximab
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Disease Progression
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives*
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Quality of Life
  • Statistics, Nonparametric
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Deoxycytidine
  • Capecitabine
  • Irinotecan
  • Cetuximab
  • Fluorouracil
  • Camptothecin