Y Munemoto1, M Nakamura2, M Takahashi3, M Kotaka4, H Kuroda5, T Kato6, N Minagawa7, S Noura8, M Fukunaga9, H Kuramochi10, T Touyama11, T Takahashi12, K Miwa13, H Satake14, S Kurosawa15, T Miura15, H Mishima16, J Sakamoto17, K Oba18, N Nagata19. 1. Department of Surgery, Fukui-ken Saiseikai Hospital, 7-1 Funabashi, Wadanaka-cho, Fukui City, Fukui, 918-8503, Japan. 2. Department of Multidisciplinary Treatment Cancer Center, Aizawa Hospital, 2-5-1 Honjou, Matsumoto City, Nagano, 390-8510, Japan. 3. Department of Gastroenterological Surgery, Yokohama Municipal Citizen's Hospital, 56 Okazawa-cho, Hodogaya-ku, Yokohama City, Kanagawa, 240-8555, Japan. 4. Gastrointestinal Cancer Center, Sano Hospital, 2-5-1 Shimizugaoka, Tarumi-ku, Kobe City, Hyogo, 655-0031, Japan. 5. Department of Surgery, Kitakyushu General Hospital, 1-1 Higashijounomachi, Kokurakita-ku, Kitakyushu City, Fukuoka, 802-8517, Japan. 6. Department of Surgery, National Hospital Organization Osaka National Hospital, 2 -1-14 Hoenzaka, Chuo-ku, Osaka City, Osaka, 540-0006, Japan; Department of Surgery, Kansai Rosai Hospital, 3 Chome-1-69 Inabaso, Amagasaki City, Hyogo, 660-8511, Japan. 7. Department of Surgery 1, The University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu City, Fukuoka, 807-8555, Japan. 8. Department of Surgery, Osaka Rosai Hospital, 1179-3 Nagasone-cho, Kita-ku, Sakai City, Osaka, 591-8025, Japan. 9. Department of Surgery, Hyogo Prefectural Nishinomiya Hospital, 13-9 Rokutanji-cho, Nishinomiya City, Hyogo, 662-0918, Japan. 10. Department of Chemotherapy Surgery, Tokyo Women's Medical University Yachiyo Medical Center, 477-96 Owada Shinden, Yachiyo City, Chiba, 276-8524, Japan. 11. Department of Surgery, Nakagami Hospital, 610 Noborikawa, Okinawa City, Okinawa, 904-2195, Japan. 12. Department of Surgical Oncology, Gifu University Hospital, 1-1 Yanagido, Gifu City, Gifu, 501-1194, Japan. 13. Department of Multidisciplinary Treatment Cancer Center, Kurume University Hospital, 67 Asahimachi, Kurume City, Fukuoka, 830-0011, Japan. 14. Department of Medical Oncology, Kobe City Medical Center General Hospital, 2-1-1 Minatojima Minamimachi, Chuo-ku, Kobe City, Hyogo, 650-0047, Japan; Cancer Treatment Center, Kansai Medical University Hospital, 2-3-1 Shinmachi, Hirakata City, Osaka, 573-1191, Japan. 15. Department of Japan Medical Affairs, Japan Oncology Business Unit, Takeda Pharmaceutical Company Limited, 2-1-1 Nihonbashi-Honcho, Chuo-ku, Tokyo, 103-8668, Japan. 16. Cancer Center, Aichi Medical University, 1-1 Yazakokarimata, Nagakute City, Aichi, 480-1195, Japan. 17. Hospital Director's Office, Tokai Central Hospital, 4-6-2 Sohara Higashijima-cho, Kakamigahara City, Gifu, 504-8601, Japan. 18. Department of Biostatistics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan. 19. Department of Surgery, Kitakyushu General Hospital, 1-1 Higashijounomachi, Kokurakita-ku, Kitakyushu City, Fukuoka, 802-8517, Japan. Electronic address: n.nagata@kitakyu-hp.or.jp.
Abstract
BACKGROUND:Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (FOLFOX) plus panitumumab therapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term administration of oxaliplatin is associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatin after FOLFOX plus panitumumab therapy can maintain efficacy and reduce PN incidence. PATIENTS AND METHODS: Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumab as induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab (group A) or to 5-FU/LV plus panitumumab (group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety. RESULTS: In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval [CI], 38.1-54.9) and 9.1 months (95% CI, 8.6-11.1) in group A, compared with 47.4% (80% CI, 39.1-55.8) and 9.3 months (95% CI, 6.0-13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%). CONCLUSION: Planned discontinuation of oxaliplatin after six cycles of mFOLFOX6 plus panitumumab is a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab. TRIAL REGISTRATION NUMBER: NCT02337946.
RCT Entities:
BACKGROUND:Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (FOLFOX) plus panitumumab therapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term administration of oxaliplatin is associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatin after FOLFOX plus panitumumab therapy can maintain efficacy and reduce PN incidence. PATIENTS AND METHODS: Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumab as induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab (group A) or to 5-FU/LV plus panitumumab (group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety. RESULTS: In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval [CI], 38.1-54.9) and 9.1 months (95% CI, 8.6-11.1) in group A, compared with 47.4% (80% CI, 39.1-55.8) and 9.3 months (95% CI, 6.0-13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%). CONCLUSION: Planned discontinuation of oxaliplatin after six cycles of mFOLFOX6 plus panitumumab is a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab. TRIAL REGISTRATION NUMBER: NCT02337946.
Authors: Dominik Paul Modest; Meinolf Karthaus; Stefan Fruehauf; Ullrich Graeven; Lothar Müller; Alexander Otto König; Ludwig Fischer von Weikersthal; Karel Caca; Albrecht Kretzschmar; Eray Goekkurt; Siegfried Haas; Annika Kurreck; Arndt Stahler; Swantje Held; Armin Jarosch; David Horst; Anke Reinacher-Schick; Stefan Kasper; Volker Heinemann; Sebastian Stintzing; Tanja Trarbach Journal: J Clin Oncol Date: 2021-09-17 Impact factor: 44.544