Primary mFOLFOX6 Plus Bevacizumab Without Resection of the Primary Tumor for Patients Presenting With Surgically Unresectable Metastatic Colon Cancer and an Intact Asymptomatic Colon Cancer: Definitive Analysis of NSABP Trial C-10

Lacks Cancer Center, St Mary's Health Care, Michigan State University, 250 Cherry St, Grand Rapids, MI 49503
Journal of Clinical Oncology (Impact Factor: 18.43). 08/2012; 30(26):3223-8. DOI: 10.1200/JCO.2012.42.4044
Source: PubMed


Major concerns surround combining chemotherapy with bevacizumab in patients with colon cancer presenting with an asymptomatic intact primary tumor (IPT) and synchronous yet unresectable metastatic disease. Surgical resection of asymptomatic IPT is controversial.

Patients and methods:
Eligibility for this prospective, multicenter phase II trial included Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1, asymptomatic IPT, and unresectable metastases. All received infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) combined with bevacizumab. The primary end point was major morbidity events, defined as surgical resection because of symptoms at or death related to the IPT. A 25% major morbidity rate was considered acceptable. Secondary end points included overall survival (OS) and minor morbidity related to IPT requiring hospitalization, transfusion, or nonsurgical intervention.

Ninety patients registered between March 2006 and June 2009: 86 were eligible with follow-up, median age was 58 years, and 52% were female. Median follow-up was 20.7 months. There were 12 patients (14%) with major morbidity related to IPT: 10 required surgery (eight, obstruction; one, perforation; and one, abdominal pain), and two patients died. The 24-month cumulative incidence of major morbidity was 16.3% (95% CI, 7.6% to 25.1%). Eleven IPTs were resected without a morbidity event: eight for attempted cure and three for other reasons. Two patients had minor morbidity events only: one hospitalization and one nonsurgical intervention. Median OS was 19.9 months (95% CI, 15.0 to 27.2 months).

This trial met its primary end point. Combining mFOLFOX6 with bevacizumab did not result in an unacceptable rate of obstruction, perforation, bleeding, or death related to IPT. Survival was not compromised. These patients can be spared initial noncurative resection of their asymptomatic IPT.

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    • "Additional therapy whether surgical resection or systemic chemotherapy was considered. Recently, neoadjuvant therapy using FOLFOX (with approved biological agent) chemotherapy was recommended as a nonsurgical management of patients with no obstructing metastatic (stage IV) colorectal cancer, and demonstrated excellent result with few complications [14]. This suggests nonsurgical chemotherapy using FOLFOX plus biological antibodies might have beneficial effect on patients with urethral metastasis from colorectal cancer. "
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    BMC Surgery 05/2014; 14(1):31. DOI:10.1186/1471-2482-14-31 · 1.40 Impact Factor
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    • "Recently, the results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Trial C-10 were published [53]. This study was a phase-2 clinical trial to investigate the safety of nonsurgical treatment when unresectable stage IV colorectal cancer patients with asymptomatic primary tumors were treated using 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) chemotherapy drugs with Bevacizumab. "
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    • "Ruo reported that 30 (29%) of the 103 patients who were initially managed without bowel resection required a subsequent operation for the palliation of complications [10]. McCahill and Poultsides reported that only those cases with complete obstruction, perforation or massive bleeding (7 to 4%), require surgery of their primary tumor [11,12]. However, there is no report about an early start of chemotherapy after resection of primary CRC. "
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