The addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastoma

Clin Cancer Res. 2011 Jun 15;17(12):4119-24. doi: 10.1158/1078-0432.CCR-11-0120. Epub 2011 Apr 29.

Abstract

Purpose: To determine if the addition of bevacizumab to radiation therapy and temozolomide, followed by bevacizumab, temozolomide, and irinotecan, for newly diagnosed glioblastoma patients is safe and effective.

Experimental design: A total of 75 patients with newly diagnosed glioblastoma were enrolled in the phase II trial that investigated the addition of bevacizumab to standard radiation therapy and daily temozolomide followed by the addition of bevacizumab and irinotecan to adjuvant temozolomide. The bevacizumab was given at 10 mg/kg every 14 days beginning a minimum of 4 weeks postcraniotomy. Two weeks after radiation therapy, the patients began 6 to 12 cycles of 5-day temozolomide with bevacizumab and irinotecan every 14 days. The primary endpoint was the proportion of patients alive 16 months after informed consent.

Results: The therapy had moderate toxicity. Three patients, one of whom had a grade 2 central nervous system hemorrhage, came off study during radiation therapy. Seventy patients started the postradiation therapy, and 16 (23%) terminated this adjuvant therapy early because of toxicity. The median overall survival was 21.2 months (95% CI: 17.2-25.4), and 65% of the patients were alive at 16 months (95% CI: 53.4-74.9). The median progression-free survival was 14.2 months (95% CI: 12-16).

Conclusion: The addition of bevacizumab to standard radiation therapy and temozolomide, followed by bevacizumab, irinotecan, and temozolomide, for the treatment of newly diagnosed glioblastoma has moderate toxicity and may improve efficacy compared with historical controls. The results from phase III trials are required before the role of bevacizumab for newly diagnosed glioblastoma is established.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal / toxicity
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use*
  • Bevacizumab
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Camptothecin / toxicity
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Dacarbazine / toxicity
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / mortality
  • Glioblastoma / radiotherapy*
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Prognosis
  • Radiotherapy
  • Survival Analysis
  • Temozolomide
  • Treatment Outcome
  • Young Adult

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Bevacizumab
  • Irinotecan
  • Dacarbazine
  • Camptothecin
  • Temozolomide