Comparison of Irinotecan and Oxaliplatin as the First-Line Therapies for Metastatic Colorectal Cancer: A Meta-analysis

Abstract

BackgroundIrinotecan (IRI) and oxaliplatin (Ox) are standard therapeutic agents of the first-line treatments for metastatic colorectal cancer (mCRC). Previous meta-analyses of randomized controlled trials (RCTs) showed that treatment with Ox-based compared with IRI-based regimens was associated with better overall survival (OS). However, these reports did not include trials of molecular targeting agents and did not take methods for the administration of concomitant drugs, such as bolus or continuous infusion of 5-fluorouracil, into account. A systematic literature review was performed to compare the efficacy and toxicity profiles between IRI- and Ox-based regimens as the first-line treatments for mCRC.MethodsThis meta-analysis used data from the Cochrane Central Register of Controlled Trials, PubMed, and SCOPUS. The primary endpoint was OS, and the secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs).ResultsNineteen trials involving 4,571 patients were included in the analysis. No statistically significant difference was observed between the two groups in terms of OS, PFS, and ORR. There was no significant heterogeneity. Regarding ≥ grade 3 AEs, IRI-based regimens were associated with a high incidence of leukopenia, febrile neutropenia, and diarrhea. Moreover, there was a high incidence of thrombocytopenia and peripheral sensory neuropathy in patients who received Ox-based regimens. In a subgroup analysis, IRI combined with bevacizumab was correlated with a better PFS (HR = 0.90, 95% CI = 0.82–0.98, P = 0.02), but not with OS.ConclusionAlthough the safety profiles of IRI- and Ox-based regimens varied, their efficacy did not significantly differ. Therefore, both regimens could be used as the first-line treatments for mCRC with consideration of the patients’ condition or toxicity profiles.

Primary tumor resection improves prognosis of unresectable carcinomas of the transverse colon including flexures with liver metastasis: a preliminary population-based analysis

“…Our analysis of the prognostic factors of unresectable CRLM patients showed that perioperative chemotherapy was a common independent prognostic factor, and the prognosis of UTCLM, UHFLM, and USFLM patients who received perioperative chemotherapy was significantly better than that of patients without perioperative chemotherapy. This did not seem to be an unexpected result, as many studies have shown the positive effect of perioperative chemotherapy on the prognosis of unresectable CRLM [ 81 – 83 ], especially when mutational status analysis has been used by some guidelines to guide the treatment and prognosis of CRLM [ 84 , 85 ]. Studies showed that not only KRAS, BRAF could guide the identification of CRLM patients who could benefit most from surgical resection [ 80 , 86 ] , but also KRAS, NRAS, BRAF, TP53, MSI, APC, and PIK3CA became important prognostic indexes to guide perioperative chemotherapy in patients with CRLM [ 87 – 91 ], and could guide the selection of further combined targeted therapy.…”

Inoperable de novo metastatic colorectal cancer with primary tumour in situ: Evaluating discordant responses to upfront systemic therapy of the primary tumours and metastatic sites and complications arising from primary tumours (experiences from an Irish Cancer Centre)

“…Oxaliplatin-containing regimens, such as FOLFOX (16,17) or XELOX (18,19) and irinotecan-containing regimens, such as FOLFIRI (20)(21)(22) and XELIRI (23)(24)(25), have both been established equally effective in terms of progression-free and overall survival as first-line palliative systemic therapy in mCRC (26). Oxaliplatin-containing regimens may be preferred over irinotecan-based regimens as first-line therapy in mCRC due to their slightly more favourable median overall survival and toxicity profiles (21,27,28), including in elderly patients (29).…”