Efficacy and safety of chronomodulated irinotecan, oxaliplatin, 5‐fluorouracil and leucovorin combination as first‐ or second‐line treatment against metastatic colorectal cancer: Results from the International EORTC 05011 Trial. Issue 10 (10th December 2020)

• Record Type: Journal Article
• Authors: Innominato, Pasquale F.; Karaboué, Abdoulaye; Focan, Christian; Chollet, Philippe; Giacchetti, Sylvie; Bouchahda, Mohamed; Ulusakarya, Ayhan; Torsello, Angela; Adam, René; Lévi, Francis A.; Garufi, Carlo
• Is Part Of: International journal of cancer. Volume 148:Issue 10(2021)
• Page Start: 2512
• Page End: 2521
• Publication Date: 2020-12-10
• Subjects: chemotherapy -- chronotherapy -- circadian -- colorectal cancer -- FOLFIRINOX; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.33422
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract: The triplet combination of irinotecan, oxaliplatin and fluorouracil is an active frontline regimen in metastatic colorectal cancer, but scarce data exist on its use as salvage treatment. We aimed at assessing its safety and efficacy profiles with its circadian‐based administration (chronoIFLO5) as either first‐ or second‐line treatment, within the time‐finding EORTC 05011 trial. Five‐day chronoIFLO5 was administered every 3 weeks in patients with PS 0, 1 or 2. It consisted of chronomodulated irinotecan (180 mg/sqm), oxaliplatin (80 mg/sqm) and fluorouracil‐leucovorin (2800 and 1200 mg/sqm, respectively). For our study, toxicity and antitumour activity were evaluated separately in first‐ and second‐line settings. Primary endpoints included Grade 3‐4 toxicity rates, best objective response rate (ORR), progression‐free survival (PFS) and overall survival (OS). One‐hundred forty‐nine and 44 patients were treated in first‐line and second‐line settings, respectively, with a total of 1138 cycles with median relative dose intensities of about 90%. Demographics were comparable in the two groups. Thirty‐six (24.7%) and 10 (22.2%) patients experienced at least one episode of severe toxicity in first line and second line, respectively. Frontline chronoIFLO5 yielded an ORR of 62.3% [95% CI: 54.2‐70.4] and resulted in median PFS and OS of 8.7 months [7.5‐9.9] and 19.9 months [15.4‐24.5]. Corresponding figures in second line were 37.5% [22.5‐52.5], 6.7 months [4.8‐8.9] and 16.3 months [11.8‐20.8]. International and prospective evaluation revealed the favourable safety and efficacy profiles of chronoIFLO5, both as frontline and as salvage treatment against metastatic colorectal cancer. In particular, encouraging activity in second line was observed, with limited haematological toxicity. Abstract : What's new? Triple chemotherapy of irinotecan, oxaliplatin and fluorouracil‐leucovorin achieves the best survival against metastatic colorectal cancer (CRC) but has worse toxicity than doublet therapy. Chronomodulation is a strategy to reduced toxicity by coordinating drug administration with the patient's circadian rhythm. Here, the authors evaluated the safety and efficacy of chronomodulated triple therapy given over a 5‐day period every 3 weeks. 149 patients received the treatment as a first‐line regimen, while 44 received it as salvage therapy. In both settings, the safety and efficacy of chronomodulated triple therapy were validated, although the optimal timing of irinotecan for minimizing toxicity remains to be determined.