Oxaliplatin/capecitabine vs oxaliplatin/infusional 5-FU in advanced colorectal cancer: the MRC COIN trial

Abstract

Background:COIN compared first-line continuous chemotherapy with the same chemotherapy given intermittently or with cetuximab in advanced colorectal cancer (aCRC).Methods:Choice between oxaliplatin/capecitabine (OxCap) and oxaliplatin/leucovorin (LV)/infusional 5-FU (OxFU) was by physician and patient choice and switching regimen was allowed. We compared OxCap with OxFU and OxCap+cetuximab with OxFU+cetuximab retrospectively in patients and examined efficacy, toxicity profiles and the effect of mild renal impairment.Results:In total, 64% of 2397 patients received OxCap(±cetuximab). Overall survival, progression free survival and overall response rate were similar between OxCap and OxFU but rate of radical surgeries was higher for OxFU. Progression free survival was longer for OxFU+cetuximab compared with OxCap+cetuximab but other efficacy measures were similar. Oxaliplatin/LV/infusional 5-FU (±cetuximab) was associated with more mucositis and infection whereas OxCap(±cetuximab) caused more gastrointestinal toxicities and palmar-plantar erythema. In total, 118 patients switched regimen, mainly due to toxicity; only 16% came off their second regimen due to intolerance. Patients with creatinine clearance (CrCl) 50–80 ml min−1 on OxCap(±cetuximab) or OxFU+cetuximab had more dose modifications than those with better renal function.Conclusions:Overall, OxFU and OxCap are equally effective in treating aCRC. However, the toxicity profiles differ and switching from one regimen to the other for poor tolerance is a reasonable option. Patients with CrCl 50–80 ml min−1 on both regimens require close toxicity monitoring.

Oral drugs in the treatment of metastatic colorectal cancer

“…[51] Subset analysis comparing CAPOX plus cetuximab and FOLFOX plus cetuximab showed a longer PFS for FOLFOX plus cetuximab and worse tolerance of CAPOX plus cetuximab with significantly more diarrhea and HFS. [52] For these reasons, anti-EGFR antibodies should preferably not be used in combination with capecitabine-based chemotherapy.…”

Phase II trial of panitumumab with irinotecan as salvage therapy for patients with advanced or recurrent colorectal cancer (TOPIC study)

“…A lack of evidence for the successful use of anti-VEGF as salvage therapy and the impressive results of using bevacizumab beyond progression (BBP) have led to certain oncologists preferring first-line anti-VEGR therapy with the BBP strategy (10,11). However, several detrimental results in anti-EGFR trials have appeared to have resulted in an aversion to using combined therapies as first-line treatment (12,13). Based on the biological synergistic effect with irinotecan, anti-EGFR tends to be combined even though it is a salvage treatment (14).…”

Optimal Sequences and Combination of Chemotherapy and Monoclonal Antibodies in the Treatment of Patients With Metastatic Colorectal Cancer

“…Так, не следует комбинировать моноклональные антите-ла к рецептору эпидермального фактора роста (EGFR) с пероральными формами фторпиримидинов (напри-мер, со схемой XELOX) или со струйными введениями фторурацила (например, с режимом FLOX). В указанных сочетаниях анти-EGFR антитела не улучшили показа-тели выживаемости пациентов [8,9]. При этом данные антитела не влияют ни на фармакокинетику фторпи-римидинов, ни на частоту осложнений при комбинации со струйным введением фторурацила или приемом ка-пецитабина, чтобы этим можно было объяснить отсут-ствие эффекта от добавления таргетных препаратов [10].…”