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Original Article
A double-blind, randomized, placebo-controlled, phase 2 study of maintenance enzastaurin with 5-fluorouracil/leucovorin plus bevacizumab after first-line therapy for metastatic colorectal cancer†
Article first published online: 27 DEC 2011
DOI: 10.1002/cncr.26692
Copyright © 2011 American Cancer Society
Additional Information
How to Cite
Wolff, R. A., Fuchs, M., Di Bartolomeo, M., Hossain, A. M., Stoffregen, C., Nicol, S. and Heinemann, V. (2012), A double-blind, randomized, placebo-controlled, phase 2 study of maintenance enzastaurin with 5-fluorouracil/leucovorin plus bevacizumab after first-line therapy for metastatic colorectal cancer. Cancer, 118: 4132–4138. doi: 10.1002/cncr.26692
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ClinicalTrials.gov identifier: NCT00612586.
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Fax: (713) 794-1807
Publication History
- Issue published online: 20 AUG 2012
- Article first published online: 27 DEC 2011
- Manuscript Accepted: 3 OCT 2011
- Manuscript Revised: 29 SEP 2011
- Manuscript Received: 23 AUG 2011
- Abstract
- Article
- References
- Cited By
Keywords:
- 5-fluorouracil/leucovorin;
- bevacizumab;
- enzastaurin;
- maintenance therapy;
- metastatic colorectal cancer
Abstract
BACKGROUND:
Enzastaurin and bevacizumab have demonstrated synergistic antitumor effects and, in phase 1 studies, the combination was well tolerated. This phase 2 study assessed enzastaurin with 5-fluorouracil/leucovorin plus bevacizumab as maintenance therapy for metastatic colorectal cancer (MCRC).
METHODS:
Patients with locally advanced or MCRC and stable or responding disease after completing 6 cycles of first-line chemotherapy randomly received a loading dose of enzastaurin 1125 mg, followed by 500 mg/d subsequent doses or placebo. Both arms received 5-fluorouracil/leucovorin (leucovorin 400 mg/m2 intravenously [IV], 5-fluorouracil 400-mg/m2 bolus, 5-fluorouracil 2400 mg/m2 IV) plus bevacizumab 5 mg/kg IV, every 2 weeks. The primary endpoint was progression-free survival (PFS), from randomization. Overall survival (OS) and PFS were also assessed from start of first-line therapy. Enrollment was stopped, and the final analysis was conducted after 73 PFS events.
RESULTS:
Fifty-eight patients were randomized to enzastaurin and 59 to placebo. For the enzastaurin and placebo arms, respectively, the median cycles received were 9 and 10, and the median PFS was 5.8 and 8.1 months (hazard ratio [HR], 1.35; 95% confidence interval [CI], 0.84-2.16; P = .896). Median OS was not calculable because of high censoring (77.6% enzastaurin; 91.5% placebo). The median PFS from start of first-line therapy was 8.9 months for enzastaurin and 11.3 months for placebo (HR, 1.39; 95% CI, 0.86-2.23; P = .913). More enzastaurin patients developed thrombosis or embolism compared with placebo (15.8% and 1.7%; P = .008). One possibly enzastaurin-related death occurred because of arrhythmia.
CONCLUSIONS:
Enzastaurin combined with bevacizumab-based therapy is tolerable, but does not improve PFS during maintenance therapy in patients with MCRC compared with bevacizumab-based therapy alone. Cancer 2012. © 2011 American Cancer Society.