Bevacizumab in Combination With Either FOLFOX-4 or XELOX-2 in First-line Treatment of Patients With Metastatic Colorectal Cancer: A Multicenter Randomized Phase II Trial of the Gruppo Oncologico dell'Italia Meridionale (GOIM 2802).

INTRODUCTION: Biweekly schedule of XELOX-2 (capecitabine plus oxaliplatin) showed interesting results in first-line therapy of patients with metastatic colorectal cancer (mCRC). Bevacizumab plus FOLFOX-4 (oxaliplatin, folinic acid, and infusional 5-fluorouracil) is among standard first-line treatment options in this setting. We performed a phase II randomized trial in order to evaluate the activity of bevacizumab plus either FOLFOX-4 or XELOX-2 in first-line therapy of patients with mCRC. MATERIALS AND METHODS: Patients with mCRC were randomized, in a 1:2 ratio, to first-line bevacizumab plus either FOLFOX-4 (Arm A), as calibration arm, or XELOX-2 (Arm B), up to 12 cycles. Patients without progression were further randomized to maintenance bevacizumab alone or with the same induction fluoropyrimidine. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival, overall survival, and toxicity. The study design was formally non-comparative, but exploratory comparison was performed. RESULTS: Forty-five patients were randomized in arm A and 87 in arm B with an ORR of 55.6% versus 48.3% (P = .43), respectively. After a median follow-up of 47.2 months, progression-free survival was 10.0 versus 9.9 months (hazard ratio, 0.96; 95% confidence interval, 0.65-1.41; P = .84) and overall survival was 29.8 versus 25.0 months (hazard ratio, 1.21; 95% confidence interval, 0.77-1.92; P = .41), respectively. The main grade 3 to 4 toxicities (% A/B) were: neutropenia 15/3 and nausea 9/5. CONCLUSION: This exploratory analysis showed that biweekly XELOX-2 plus bevacizumab has a comparable ORR with FOLFOX-4 plus bevacizumab in patients with mCRC.

The potential role of nintedanib in treating colorectal cancer.

INTRODUCTION: Angiogenesis leads to the growth, progression, and metastases of a variety of solid tumors, including metastatic colorectal cancer (mCRC), involving particularly the family of vascular endothelial growth factors (VEGF) and their receptors (VEGFR). Several anti-angiogenic inhibitors are already registered for mCRC therapy: bevacizumab, aflibercept, ramucirumab, regorafenib. Nintedanib is a new triple angiokinase oral inhibitor that potently blocks the proangiogenic pathways mediated by VEGFR, platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). Areas covered: The current state-of-the-art of anti-angiogenic inhibitors employed in the treatment mCRC patients, and in particular the role of nintedanib in this setting, is reviewed and discussed here. A structured search of bibliographic databases for peer-reviewed research literature and of main meetings using a focused review question was undertaken. Expert opinion: In first-line therapy, a phase II randomized trial showed that nintedanib plus chemotherapy was not inferior to the bevacizumab-based regimen. In heavily pretreated mCRC patients nintedanib improved some outcomes. During the natural history of mCRC resistances to anti-angiogenic therapies can set in and in this context, nintedanib, due to its triple inhibition, might play a role in compensatory angiogenesis overcoming the resistance developed due to VEGF directed therapy.

Combined modality treatments in pancreatic cancer.

INTRODUCTION: Of all the carcinomas, pancreatic carcinoma (PC) has the highest mortality rate, with a 1- and 5-year survival rate of 25% and less than 5% respectively. This is regardless of the stage at diagnosis. AREAS COVERED: In this review relevant literature assessing the evidence regarding preoperative and adjuvant chemoradiotherapy (CRT) is discussed. Furthermore, new therapeutic approaches are summarized, while the future direction regarding the multimodality approach to PC is also discussed. EXPERT OPINION: The role of combined-modality therapy for PC is continuously evolving. There have been several recent developments, as well as the completion of major, multi-institutional clinical trials. One of the challenges for the busy clinician is to appreciate the variation in staging, surgical expertise, and application of either definitive CRT or neo-adjuvant CRT for local and/or borderline disease.