Article

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: 17.88). 08/2012; 30(26):3223-8. DOI: 10.1200/JCO.2012.42.4044
Source: PubMed

ABSTRACT PURPOSE 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. Results 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). CONCLUSION 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.

0 Followers
 · 
144 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The diagnosis of stage IV colorectal cancer was once associated with a uniformly grim prognosis. Over the last 20 years, advances in chemotherapeutics, surgical technique, and surgical adjuncts have dramatically broadened treatment options and improved outcomes. Among current treatment options, surgery remains the key component of any multidisciplinary approach with surgical data demonstrating the longest survivorship. This review will summarize current and developing surgical advances in the treatment of metastatic colorectal cancer. Specifically, we will discuss how surgical interventions fit within the greater context of a multi-modality approach, as well as, the specific, recent innovations in the surgical management of hepatic and extrahepatic metastases.
    Current Oncology Reports 04/2015; 17(4):437. DOI:10.1007/s11912-015-0437-1 · 2.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multiple new treatment options for metastatic colorectal cancer have been developed over the past 2 decades, including conventional chemotherapy and agents directed against vascular endothelial growth factor and epidermal growth factor receptor. Combination regimens, integrated with surgical approaches, have led to an increase in median survival, and a minority of patients with resectable disease can survive for years. Clinical decision-making therefore requires a strategic, biomarker-based multidisciplinary approach to maximize life expectancy and quality of life. This review describes systemic approaches to the treatment of patients with metastatic colorectal cancer, including integration with liver resection, other liver-directed therapies, and primary resection. Copyright © 2015 Elsevier Inc. All rights reserved.
    Surgical Oncology Clinics of North America 01/2014; 24(1). DOI:10.1016/j.soc.2014.09.006 · 1.67 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A previous pivotal Phase III study (NO16966) demonstrated the benefit of the addition of bevacizumab (BV) to oxaliplatin-based regimens in metastatic colorectal cancer (MCRC). Our study evaluated the safety and efficacy of three oxaliplatin-based chemotherapy regimens (FOLFOX4 [intravenous twice-bolus and twice-infusional 5-fluorouracil/folinic acid plus oxaliplatin], mFOLFOX6 [intravenous once-bolus and once-infusional 5-fluorouracil/folinic acid plus oxaliplatin], and XELOX [capecitabine plus oxaliplatin]) plus BV in the first-line treatment of MCRC patients. Patients with MCRC who started treatment between June 2007 and September 2010 were evaluated in this retrospective cohort study. We also evaluated early objective tumor response (EOTR) within 12 weeks, which was defined as a relative change of ≥30% in the sum of the longest diameters of target lesions when compared with baseline. The primary study endpoints were progression-free survival (PFS) and response rate. A total of 185 patients received the following chemotherapy: FOLFOX4 + BV (FF4 arm, n=85), mFOLFOX6 + BV (FF6 arm, n=40), and XELOX + BV (XELOX arm, n=60). The overall response rates were 61.2%, 72.5%, and 75.0% (95% confidence interval: 50.6%-71.8%, 58.0%-87.0%, and 63.7%-86.3%). Median PFS was 18.0, 15.5, and 13.7 months, respectively (log-rank: P=0.254; data cut-off: May 2013). Patients with EOTR (n=117) had significantly better PFS than those without-EOTR (n=68) (17.5 versus 12.7 months, P=0.004). This study suggests that these three BV plus oxaliplatin-based treatments might have comparable benefit in terms of tumor response and PFS. Moreover, EOTR may be a predictive factor for PFS in patients with MCRC.
    OncoTargets and Therapy 03/2015; 8:529-537. DOI:10.2147/OTT.S77190 · 1.34 Impact Factor