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Abstract

Irinotecan has shown activity in advanced colorectal cancer resistant to leucovorin and fluorouracil. Preclinical experiments on cell cultures and human tumor xenografts indicated potential synergy when combining irinotecan and fluorouracil. We designed a new regimen combining leucovorin, fluorouracil, irinotecan, and hydroxyurea (FOLFIRI-2) and conducted a phase II study to establish its efficacy and tolerance in advanced colorectal cancer refractory to fluorouracil and oxaliplatin. Treatment was repeated every 2 weeks and consisted of leucovorin 400 mg/m2 on day 1, immediately followed by 46 hours of continuous infusion of fluorouracil 2,000 mg/m2, irinotecan 180 mg/m2 on day 3, and hydroxyurea 1,500 mg the day before leucovorin, and on days 1 and 2. Treatment was continued until progression or limiting toxicity. Twenty-nine heavily pretreated patients entered the study. Five patients achieved an objective response (17%), and 12 obtained stabilization of disease or minor response (52%). Five patients failed to continue treatment (17%) because of toxicity or worsening condition. From the start of FOLFIRI-2 treatment, median progression-free survival was 4.1 months and median survival was 9.7 months. Grade III/IV National Cancer Institute-Common Toxicity Criteria toxicities were nausea 17%, diarrhea 31%, mucositis 14%, neutropenia 52%, and febrile neutropenia 14%. FOLFIRI-2 achieved a good rate of response and stabilization in heavily pretreated patients despite significant toxicity.

FOLFIRI3-aflibercept in previously treated patients with metastatic colorectal cancer

“…In the irinotecan pre-exposed population, patients received FOLFIRI3-aflibercept as salvage therapy. Yet, median PFS and OS were 5.7 mo and 14.3 mo, respectively, and were comparable to figures observed in second-line trials[ 8 , 15 ].…”

“…Standard second-line therapy in patients with previously treated metastatic colorectal cancer (mCRC) is doublet fluoropyrimidine-based chemotherapy with either irinotecan (FOLFIRI) or oxaliplatin (FOLFOX), depending on the regimen used in first-line, in association with antiangiogenic agents ( e.g ., bevacizumab, aflibercept, ramucirumab) or anti-EGFR agents in absence of RAS tumor gene mutation ( e.g ., cetuximab, panitumumab)[ 1 - 8 ].…”

Bifractionated CPT-11 with LV5FU2 infusion (FOLFIRI-3) in combination with bevacizumab: clinical outcomes in first-line metastatic colorectal cancers according to plasma angiopoietin-2 levels

“…In line with the above hypothesis, several studies showed that a delayed administration of irinotecan increases FOLFIRI cytotoxicity. FOLFIRI2 regimen (irinotecan delivery at the end of a modified LV5FU2 chemotherapy) in heavily pretreated CRC patients induced promising objective responses but also a limiting hematologic toxicity [19]. As reported here and in previous studies, FOLFIRI3 has a more appropriate toxicity profile [12].…”

Bevacizumab plus FOLFOX or FOLFIRI regimens on patients with unresectable liver-only metastases of metastatic colorectal cancer

“…60%. [ 26 ] Seventeen percent objective responses were observed in Mabro's study for FOLFIRI regimen,[ 27 ] and other studies reported response rate for FOLFIRI regimen as followed; Douillard et al . 40.8%,[ 28 ] Tourniguand et al .…”