Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Kodai Takemori , Kazuma Kobayashi , Yusuke Inoue , Satomi Okada , Toshiyuki Adachi , Akihiko Soyama , Tomohiko Adachi , Kengo Kanetaka , Susumu Eguchi
Background: As treatment for unresectable advanced/recurrent colorectal cancer (ARCC), the introduction of doublet chemotherapy, represented by FOLFOX/FOLFIRI, and molecular-targeting agents, such as anti-VEGF antibody and anti-EGFR antibody, has given ARCC patients a more than three years’ survival. Triplet chemotherapy, such as FOLFOXIRI ± Bevacizumab or Panitumumab, has already been used in daily practice. These regimens with powerful anti-tumor effects have enabled conversion from unresectable to resectable, giving patients a longer survival than those without conversion. Therefore, we explored the ideal regimen for conversion, focusing on FOLFOXIRI ± X. Methods: We retrospectively reviewed unresectable ARCC patients treated with FOLFOXIRI ± X (X:Bmab, n=24; Pmab, n=1; alone, n=2; ) between February 2015 and December 2022. The results were compared to those of patients who received other regimens (OTHERS; n=212). Results: The median overall survival (OS) was 1072 days. Forty-nine patients acquired conversion. The patients with conversion had a longer progression-free survival and OS than those without conversion (p<0.0001 and <0.0001, respectively). Conversion rates were 37.0% in FOLFOXIRI ± X vs. 18.4% in OTHERS (p=0.0238), while response rates were 59.3% in FOLFOXIRI ± X vs. 35.8% in OTHERS (p=0.0185). The RAS wild-type group conversion rates were 30.0% in FOLFOXIRI ± X vs. 20.6% in OTHERS, while 50.0% in FOLFOXIRI ± X vs. 15.3% in OTHERS in RAS mutant group. Anti-EGFR antibody +L-OHP-based doublet chemotherapy accounted for conversion in 35.3% of the RAS wild-type group. Anti-VEGF antibody + L-OHP based doublet chemotherapy attained 29.1% conversion rate in RAS mutant group. Molecular targeting agent+doublet or triplet regimens were essential for conversion. FOLFOXIRI ± X achieved a 88.9% disease control rate, with palliation of symptoms due to a high tumor burden in 10 of 13 cases. Conclusions: Based on these results, FOLFOXIRI ± X may be an ideal candidate for achieving conversion in first-line treatment of unresectable ARCC.
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