Phase II Multicenter Trial of Bevacizumab Plus Fluorouracil and Leucovorin in Patients With Advanced Refractory Colorectal Cancer: An NCI Treatment Referral Center Trial TRC-0301
- 20 July 2006
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 24 (21), 3354-3360
- https://doi.org/10.1200/jco.2005.05.1573
Abstract
Purpose To provide bevacizumab (BV) -based therapy to patients with advanced colorectal cancers (CRC) who had exhausted standard chemotherapy options, and to evaluate the response to BV combined with fluorouracil (FU) and leucovorin (LV) in this patient population. Patients and Methods This was a multicenter, single-arm treatment trial conducted under the National Cancer Institute Treatment Referral Center network nationwide. Patients were treated with BV 5 mg/kg every 2 weeks combined with FU/LV; FU was administered by bolus or continuous infusion. Eligibility criteria included advanced CRC that had progressed after irinotecan- and oxaliplatin-based chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 2, and absence of thromboembolism. The primary end point was objective response rate (RR) in the first 100 assessable patients. All patients received follow-up for toxicity and survival. Results Due to rapid accrual, a total of 350 patients were enrolled at 32 participating sites nationwide by October 2003. In the initially planned cohort of 100 assessable patients, the objective RR was 4% (95% CI, 1.1% to 9.9%) by investigators' assessment and 1% (95% CI, 0% to 5.5%) based on independent review; median progression-free survival was 3.5 months and median overall survival was 9.0 months. The safety profile was similar to prior BV trials in CRC. Grade 3 to 4 hemorrhage occurred in 5% of patients, including 3.8% with bleeding in the GI tract. Other adverse events such as hypertension, thrombosis, and bowel perforation were also observed at rates consistent with other studies. Conclusion For patients with advanced CRC that had progressed after both irinotecan-based and oxaliplatin-based chemotherapy regimens, the combination of BV and FU/LV was associated with rare objective responses.Keywords
This publication has 10 references indexed in Scilit:
- Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal CancerNew England Journal of Medicine, 2004
- Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal CancerNew England Journal of Medicine, 2004
- Phase II Trial of Cetuximab in Patients With Refractory Colorectal Cancer That Expresses the Epidermal Growth Factor ReceptorJournal of Clinical Oncology, 2004
- A Randomized Controlled Trial of Fluorouracil Plus Leucovorin, Irinotecan, and Oxaliplatin Combinations in Patients With Previously Untreated Metastatic Colorectal CancerJournal of Clinical Oncology, 2004
- Superiority of Oxaliplatin and Fluorouracil-Leucovorin Compared With Either Therapy Alone in Patients With Progressive Colorectal Cancer After Irinotecan and Fluorouracil-Leucovorin: Interim Results of a Phase III TrialJournal of Clinical Oncology, 2003
- Phase II, Randomized Trial Comparing Bevacizumab Plus Fluorouracil (FU)/Leucovorin (LV) With FU/LV Alone in Patients With Metastatic Colorectal CancerJournal of Clinical Oncology, 2003
- Irinotecan plus Fluorouracil and Leucovorin for Metastatic Colorectal CancerNew England Journal of Medicine, 2000
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000
- Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancerThe Lancet, 1998
- Paclitaxel for platinum-refractory ovarian cancer: results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Center 9103.Journal of Clinical Oncology, 1993