First-line chemotherapy for mCRC—a review and evidence-based algorithm

Abstract

The response to first-line therapy is a primary determinant of outcome in patients with metastatic colorectal cancer (mCRC), for three main reasons: effective upfront therapy provides a unique opportunity to cure some patients; can be crucial in delaying disease progression and achieving symptom relief; and can improve patient eligibility for, and the effectiveness of, further treatments. In the past decade, decision-making regarding the choice of first-line therapy for mCRC has been complicated by the availability of many different options without a definitive consensus on a specific standard of care (despite major advances in categorizing predictive molecular disease subtypes). Most of the efforts of the scientific community have been directed at establishing the best biologic agent to be combined with a chemotherapy doublet, although a different branch of research has produced new data that underscore the importance of defining the optimal chemotherapy backbone. Herein, we review the key clinical trials completed in the past 10 years that have investigated and compared the use of chemotherapy doublets, triplets, and monotherapies, with or without molecularly targeted biologic agents, in the first-line treatment of patients with mCRC. Our examination of the literature led us to propose a new patient-oriented algorithm to guide clinicians' decisions on the best choice of upfront therapy for mCRC.

The synthetic lethal killing of RAD54B-deficient colorectal cancer cells by PARP1 inhibition is enhanced with SOD1 inhibition

“…Accordingly, we performed both single and dual agent dose response experiments involving BMN673 and LCS-1, a recently identified SOD1 inhibitor [44]. As a control, we included 5-FU, a classical frontline drug frequently employed in combinatorial approaches in CRC [45] that does not induce SL killing in RAD54B -deficient cells. Based on Combenefit analyses, the BMN673 plus 5-FU combination showed no synergy and was merely additive (Figure 5A).…”

Immunotherapy in the treatment of colorectal cancer: a new kid on the block

“…Nevertheless, about 50% of patients develops metastases during the course of their disease. In these patients, chemotherapy (fluoropyrimidines, oxaliplatin and irinotecan) with biological agent [anti-vascular endothelial growth factor (anti-VEGF), anti-epithelial growth factor receptor (anti-EGFR) and multikinase inhibitor such as regorafenib] remains the standard of care, with median overall survival approaching 30 months [4] . The molecular characterization of colorectal cancer has led to the identification of favorable and unfavorable immunological features linked to clinical outcome [5] .…”

Synergistic inhibition of sunitinib and ethaselen against human colorectal cancer cells proliferation

“…In the past decades, multiple chemotheraputic strategies have been widely used, such as FOLFIRI (5-FU, leucovorin and irinotecan) and FOLFOX (5-FU, leucovorin and oxaliplatin) with or without molecular targeted agents. The median overall survival has notably increased from 12 months with 5-FU-based standard care, to around 30 months in the clinical trials with chemotherapy plus bevacizumab or cetuximab [12]. Nonetheless, the 5-year survival rates of patients with metastatic CRC still remains below 8% [13].…”