XELOX and bevacizumab followed by single-agent bevacizumab as maintenance therapy as first-line treatment in elderly patients with advanced colorectal cancer: The boxe study

Gerardo Rosati, Antonio Avallone, Giuseppe Aprile, Alfredo Butera, Giorgio Reggiardo, Domenico Bilancia

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose: The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) in patients with metastatic colorectal cancer (CRC). An increased risk of arterial thromboembolic events has been observed in some trials in older patients, and the potential benefit of a maintenance therapy with bevacizumab alone has not been clearly demonstrated. This phase II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab followed by bevacizumab alone in elderly patients with advanced CRC. Methods: Treatment consisted of bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1, plus capecitabine 1,000 mg/m2 twice daily on days 1-14, every 3 weeks up to a maximum of 8 cycles. Patients then received maintenance therapy consisting of bevacizumab alone (7.5 mg/kg) once every 3 weeks up to disease progression. The primary study end-points were safety and response rate. Results: A total of 44 patients were recruited. In an intention-to-treat analysis, the overall response rate was 52 % [95 % confidence interval (CI) 37 to 68 %], with 86 % of patients achieving disease control. Median PFS and overall survival were 11.5 months (95 % CI 10.0-12.9 months) and 19.3 months (95 % CI 16.5-22.1 months), respectively. In all, 10 patients (23 %) had grade 3/4 adverse events (AEs), the most common being diarrhea (9 %), neutropenia (7 %), peripheral neuropathy (7 %), and stomatitis (7 %). No patients died because of treatment-related AEs. The rate of bevacizumab-related AEs (hypertension, thromboembolic events, and gastrointestinal perforation) was consistent with that reported earlier in the general CRC population. Conclusion: The combination of XELOX and bevacizumab is effective and has a manageable tolerability profile when administered to elderly patients with advanced CRC. Maintenance therapy with single-agent bevacizumab may be considered to extend PFS in this setting of patients.

Original languageEnglish
Pages (from-to)257-264
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume71
Issue number1
DOIs
Publication statusPublished - Jan 2013

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Colorectal Neoplasms
oxaliplatin
Disease-Free Survival
Therapeutics
Confidence Intervals
Disease control
XELOX
Bevacizumab
Chemotherapy
Safety
Stomatitis
Intention to Treat Analysis
Peripheral Nervous System Diseases
Neutropenia
Disease Progression
Diarrhea
Hypertension
Drug Therapy
Survival
Population

Keywords

  • Bevacizumab
  • Colorectal cancer
  • Elderly patients
  • Maintenance therapy
  • XELOX

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

XELOX and bevacizumab followed by single-agent bevacizumab as maintenance therapy as first-line treatment in elderly patients with advanced colorectal cancer : The boxe study. / Rosati, Gerardo; Avallone, Antonio; Aprile, Giuseppe; Butera, Alfredo; Reggiardo, Giorgio; Bilancia, Domenico.

In: Cancer Chemotherapy and Pharmacology, Vol. 71, No. 1, 01.2013, p. 257-264.

Research output: Contribution to journalArticle

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abstract = "Purpose: The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) in patients with metastatic colorectal cancer (CRC). An increased risk of arterial thromboembolic events has been observed in some trials in older patients, and the potential benefit of a maintenance therapy with bevacizumab alone has not been clearly demonstrated. This phase II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab followed by bevacizumab alone in elderly patients with advanced CRC. Methods: Treatment consisted of bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1, plus capecitabine 1,000 mg/m2 twice daily on days 1-14, every 3 weeks up to a maximum of 8 cycles. Patients then received maintenance therapy consisting of bevacizumab alone (7.5 mg/kg) once every 3 weeks up to disease progression. The primary study end-points were safety and response rate. Results: A total of 44 patients were recruited. In an intention-to-treat analysis, the overall response rate was 52 {\%} [95 {\%} confidence interval (CI) 37 to 68 {\%}], with 86 {\%} of patients achieving disease control. Median PFS and overall survival were 11.5 months (95 {\%} CI 10.0-12.9 months) and 19.3 months (95 {\%} CI 16.5-22.1 months), respectively. In all, 10 patients (23 {\%}) had grade 3/4 adverse events (AEs), the most common being diarrhea (9 {\%}), neutropenia (7 {\%}), peripheral neuropathy (7 {\%}), and stomatitis (7 {\%}). No patients died because of treatment-related AEs. The rate of bevacizumab-related AEs (hypertension, thromboembolic events, and gastrointestinal perforation) was consistent with that reported earlier in the general CRC population. Conclusion: The combination of XELOX and bevacizumab is effective and has a manageable tolerability profile when administered to elderly patients with advanced CRC. Maintenance therapy with single-agent bevacizumab may be considered to extend PFS in this setting of patients.",
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AU - Avallone, Antonio

AU - Aprile, Giuseppe

AU - Butera, Alfredo

AU - Reggiardo, Giorgio

AU - Bilancia, Domenico

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N2 - Purpose: The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) in patients with metastatic colorectal cancer (CRC). An increased risk of arterial thromboembolic events has been observed in some trials in older patients, and the potential benefit of a maintenance therapy with bevacizumab alone has not been clearly demonstrated. This phase II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab followed by bevacizumab alone in elderly patients with advanced CRC. Methods: Treatment consisted of bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1, plus capecitabine 1,000 mg/m2 twice daily on days 1-14, every 3 weeks up to a maximum of 8 cycles. Patients then received maintenance therapy consisting of bevacizumab alone (7.5 mg/kg) once every 3 weeks up to disease progression. The primary study end-points were safety and response rate. Results: A total of 44 patients were recruited. In an intention-to-treat analysis, the overall response rate was 52 % [95 % confidence interval (CI) 37 to 68 %], with 86 % of patients achieving disease control. Median PFS and overall survival were 11.5 months (95 % CI 10.0-12.9 months) and 19.3 months (95 % CI 16.5-22.1 months), respectively. In all, 10 patients (23 %) had grade 3/4 adverse events (AEs), the most common being diarrhea (9 %), neutropenia (7 %), peripheral neuropathy (7 %), and stomatitis (7 %). No patients died because of treatment-related AEs. The rate of bevacizumab-related AEs (hypertension, thromboembolic events, and gastrointestinal perforation) was consistent with that reported earlier in the general CRC population. Conclusion: The combination of XELOX and bevacizumab is effective and has a manageable tolerability profile when administered to elderly patients with advanced CRC. Maintenance therapy with single-agent bevacizumab may be considered to extend PFS in this setting of patients.

AB - Purpose: The addition of bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) in patients with metastatic colorectal cancer (CRC). An increased risk of arterial thromboembolic events has been observed in some trials in older patients, and the potential benefit of a maintenance therapy with bevacizumab alone has not been clearly demonstrated. This phase II study was designed to evaluate the efficacy and safety of XELOX (capecitabine plus oxaliplatin) plus bevacizumab followed by bevacizumab alone in elderly patients with advanced CRC. Methods: Treatment consisted of bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m2 on day 1, plus capecitabine 1,000 mg/m2 twice daily on days 1-14, every 3 weeks up to a maximum of 8 cycles. Patients then received maintenance therapy consisting of bevacizumab alone (7.5 mg/kg) once every 3 weeks up to disease progression. The primary study end-points were safety and response rate. Results: A total of 44 patients were recruited. In an intention-to-treat analysis, the overall response rate was 52 % [95 % confidence interval (CI) 37 to 68 %], with 86 % of patients achieving disease control. Median PFS and overall survival were 11.5 months (95 % CI 10.0-12.9 months) and 19.3 months (95 % CI 16.5-22.1 months), respectively. In all, 10 patients (23 %) had grade 3/4 adverse events (AEs), the most common being diarrhea (9 %), neutropenia (7 %), peripheral neuropathy (7 %), and stomatitis (7 %). No patients died because of treatment-related AEs. The rate of bevacizumab-related AEs (hypertension, thromboembolic events, and gastrointestinal perforation) was consistent with that reported earlier in the general CRC population. Conclusion: The combination of XELOX and bevacizumab is effective and has a manageable tolerability profile when administered to elderly patients with advanced CRC. Maintenance therapy with single-agent bevacizumab may be considered to extend PFS in this setting of patients.

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