Hélène Bellio, Nicolas Roussot, Aurélie Bertaut, Alice Hervieu, Sylvie Zanetta, Zoe Tharin, Julie Vincent, Leila Bengrine, Audrey Hennequin, Jean-Florian Guion, Axelle Boudrant, Thomas Collot, Francois Ghiringhelli, Jean-David Fumet
{"title":"FOLFIRINOX-3联合贝伐单抗（bFOLFIRINOX3）治疗化疗难治性转移性结直肠癌：一项多中心II期试验","authors":"Hélène Bellio, Nicolas Roussot, Aurélie Bertaut, Alice Hervieu, Sylvie Zanetta, Zoe Tharin, Julie Vincent, Leila Bengrine, Audrey Hennequin, Jean-Florian Guion, Axelle Boudrant, Thomas Collot, Francois Ghiringhelli, Jean-David Fumet","doi":"10.1080/14796694.2025.2461446","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>A phase I study of FOLFIRINOX3-bevacizumab (bFOLFIRINOX3)defined the RP2D for irinotecan at 70 mg/m² and showed promising activity. This phase II trial aimed to evaluate the efficacy of bFOLFIRINOX-3 in chemorefractory metastatic colorectal cancer (mCRC).</p><p><strong>Methods: </strong>In phase II, chemorefractory mCRC were enrolled. The regimen tested consisted of bevacizumab (5 mg/kg), folinic acid(400 mg/m²), 5-fluorouracil (2400 mg/m² for 46 h), oxaliplatin (85 mg/m²) and irinotecan (70 mg/m² administered before and after infusion of 5-fluorouracil). The primary endpoint was efficacy defined by 2-month progression-free survival(PFS). Secondary endpoints included objective response, median PFS, overall survival (OS) and toxicity.</p><p><strong>Results: </strong>32 patients were enrolled (October 2018 to December 2022); median age 62.5 years (range 32-78). The majority had been treated with several previous lines of chemotherapy (median 3, range [1-8]). Median follow up was 12 months (range [1.5-12]). Two-month PFS was 96.9%. Best objective response rate (ORR) was 28.1%. Median PFS was 9.4 months (95%CI [6.9;11.5]) and median OS was not reached (95% [11.6; NR]). Grade 3 adverse events occurred in 81.2%; mostly diarrhea (37.5%) and neutropenia (12.5%). Grade 3 diarrhea consistently resolved after irinotecan dose reduction. The most common drug-related adverse events (all grades) were diarrhea (96.9%), fatigue (68.8%), nausea (68.7%), anemia (56.3%), peripheral neuropathy (53.4%) and thrombopenia (40.6%).</p><p><strong>Conclusion: </strong>The combination of bFOLFIRINOX-3 yielded 2-month PFS of 96.9% and best ORR of 28.1%, and was well tolerated. These results are promising in chemotherapy refractory mCRC and provide a rationale for future randomized phase III trials.</p><p><strong>Clinical trial registration: </strong>NCT03795311 (clinicaltrials.gov).</p>","PeriodicalId":12672,"journal":{"name":"Future oncology","volume":" ","pages":"699-706"},"PeriodicalIF":3.0000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881852/pdf/","citationCount":"0","resultStr":"{\"title\":\"FOLFIRINOX-3 plus bevacizumab (bFOLFIRINOX3) in chemo-refractory metastatic colorectal cancer: a multicenter phase II trial.\",\"authors\":\"Hélène Bellio, Nicolas Roussot, Aurélie Bertaut, Alice Hervieu, Sylvie Zanetta, Zoe Tharin, Julie Vincent, Leila Bengrine, Audrey Hennequin, Jean-Florian Guion, Axelle Boudrant, Thomas Collot, Francois Ghiringhelli, Jean-David Fumet\",\"doi\":\"10.1080/14796694.2025.2461446\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>A phase I study of FOLFIRINOX3-bevacizumab (bFOLFIRINOX3)defined the RP2D for irinotecan at 70 mg/m² and showed promising activity. This phase II trial aimed to evaluate the efficacy of bFOLFIRINOX-3 in chemorefractory metastatic colorectal cancer (mCRC).</p><p><strong>Methods: </strong>In phase II, chemorefractory mCRC were enrolled. The regimen tested consisted of bevacizumab (5 mg/kg), folinic acid(400 mg/m²), 5-fluorouracil (2400 mg/m² for 46 h), oxaliplatin (85 mg/m²) and irinotecan (70 mg/m² administered before and after infusion of 5-fluorouracil). The primary endpoint was efficacy defined by 2-month progression-free survival(PFS). Secondary endpoints included objective response, median PFS, overall survival (OS) and toxicity.</p><p><strong>Results: </strong>32 patients were enrolled (October 2018 to December 2022); median age 62.5 years (range 32-78). The majority had been treated with several previous lines of chemotherapy (median 3, range [1-8]). Median follow up was 12 months (range [1.5-12]). Two-month PFS was 96.9%. Best objective response rate (ORR) was 28.1%. Median PFS was 9.4 months (95%CI [6.9;11.5]) and median OS was not reached (95% [11.6; NR]). Grade 3 adverse events occurred in 81.2%; mostly diarrhea (37.5%) and neutropenia (12.5%). Grade 3 diarrhea consistently resolved after irinotecan dose reduction. The most common drug-related adverse events (all grades) were diarrhea (96.9%), fatigue (68.8%), nausea (68.7%), anemia (56.3%), peripheral neuropathy (53.4%) and thrombopenia (40.6%).</p><p><strong>Conclusion: </strong>The combination of bFOLFIRINOX-3 yielded 2-month PFS of 96.9% and best ORR of 28.1%, and was well tolerated. These results are promising in chemotherapy refractory mCRC and provide a rationale for future randomized phase III trials.</p><p><strong>Clinical trial registration: </strong>NCT03795311 (clinicaltrials.gov).</p>\",\"PeriodicalId\":12672,\"journal\":{\"name\":\"Future oncology\",\"volume\":\" \",\"pages\":\"699-706\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-03-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11881852/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Future oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/14796694.2025.2461446\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/2/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14796694.2025.2461446","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
FOLFIRINOX-3 plus bevacizumab (bFOLFIRINOX3) in chemo-refractory metastatic colorectal cancer: a multicenter phase II trial.
Purpose: A phase I study of FOLFIRINOX3-bevacizumab (bFOLFIRINOX3)defined the RP2D for irinotecan at 70 mg/m² and showed promising activity. This phase II trial aimed to evaluate the efficacy of bFOLFIRINOX-3 in chemorefractory metastatic colorectal cancer (mCRC).
Methods: In phase II, chemorefractory mCRC were enrolled. The regimen tested consisted of bevacizumab (5 mg/kg), folinic acid(400 mg/m²), 5-fluorouracil (2400 mg/m² for 46 h), oxaliplatin (85 mg/m²) and irinotecan (70 mg/m² administered before and after infusion of 5-fluorouracil). The primary endpoint was efficacy defined by 2-month progression-free survival(PFS). Secondary endpoints included objective response, median PFS, overall survival (OS) and toxicity.
Results: 32 patients were enrolled (October 2018 to December 2022); median age 62.5 years (range 32-78). The majority had been treated with several previous lines of chemotherapy (median 3, range [1-8]). Median follow up was 12 months (range [1.5-12]). Two-month PFS was 96.9%. Best objective response rate (ORR) was 28.1%. Median PFS was 9.4 months (95%CI [6.9;11.5]) and median OS was not reached (95% [11.6; NR]). Grade 3 adverse events occurred in 81.2%; mostly diarrhea (37.5%) and neutropenia (12.5%). Grade 3 diarrhea consistently resolved after irinotecan dose reduction. The most common drug-related adverse events (all grades) were diarrhea (96.9%), fatigue (68.8%), nausea (68.7%), anemia (56.3%), peripheral neuropathy (53.4%) and thrombopenia (40.6%).
Conclusion: The combination of bFOLFIRINOX-3 yielded 2-month PFS of 96.9% and best ORR of 28.1%, and was well tolerated. These results are promising in chemotherapy refractory mCRC and provide a rationale for future randomized phase III trials.
期刊介绍：
Future Oncology (ISSN 1479-6694) provides a forum for a new era of cancer care. The journal focuses on the most important advances and highlights their relevance in the clinical setting. Furthermore, Future Oncology delivers essential information in concise, at-a-glance article formats - vital in delivering information to an increasingly time-constrained community.
The journal takes a forward-looking stance toward the scientific and clinical issues, together with the economic and policy issues that confront us in this new era of cancer care. The journal includes literature awareness such as the latest developments in radiotherapy and immunotherapy, concise commentary and analysis, and full review articles all of which provide key findings, translational to the clinical setting.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
