Toshi Takaoka1, Tetsuo Kimura1, Rai Shimoyama2, Shunji Kawamoto3, Kazuki Sakamoto4, Fuminori Goda5, Hiroshi Miyamoto1, Yuji Negoro6, Akihito Tsuji7, Koji Yoshizaki8, Takahiro Goji1, Shinji Kitamura1, Hiromi Yano1, Koichi Okamoto1, Masako Kimura1, Toshiya Okahisa1, Naoki Muguruma1, Yoshiro Niitsu9, Tetsuji Takayama10. 1. Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan. 2. Department of Surgery, Shonan Kamakura General Hospital, 1370-1, Okamoto, Kamakura, Kanagawa, 247-8533, Japan. 3. Department of Surgery, Fukuoka Tokushukai Medical Center, 4-5, Sugukita, Kasuga, Fukuoka, 816-0864, Japan. 4. Department of Surgery, Kishiwada Tokushukai Hospital, 4-27-1, Kamori-cho, Kishiwada, Osaka, 596-8522, Japan. 5. Department of Integrated Medicine, Kagawa University Hospital, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan. 6. Kochi Health Sciences Center, 2125-1 Ike, Kochi, 781-8555, Japan. 7. Kobe City Medical Center General Hospital, 2-2-1, Minatojima, Minamimachi, Chuo-ku, Kobe, 650-0047, Japan. 8. Gastroenterology Center, Sapporo Higashi Tokushukai Hospital, 14-3-1, Higashi, Kita 33-jo, Higashi-ku, Sapporo, 065-0033, Japan. 9. Department of Molecular Target Exploration, Sapporo Medical University School of Medicine, South-1, West-17, Chuo-ku, Sapporo, 060-8556, Japan. 10. Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan. takayama@tokushima-u.ac.jp.
Abstract
BACKGROUND: Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC. METHODS: Main inclusion criteria were patients with wild-type KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/kg) and irinotecan (100 mg/m(2)) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was the feasibility of the therapy. The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 36 patients received protocol treatment in eight centers. Of these, 23 patients (63.9 %) completed protocol treatment, demonstrating achievement of the primary endpoint. The most frequent grade 3/4 toxicities were diarrhea (16.7 %), acne-like rash (13.9 %), and neutropenia (11.1 %). The overall RR was 33.3 % (12/36). Of these patients, five underwent conversion surgery. Median PFS and OS were 9.5 months (95 % CI 3.5-15.4 months) and 20.1 months (95 % CI 16.7-23.2 months), respectively. CONCLUSION: IRIS plus panitumumab has an acceptable toxicity profile and a promising efficacy in patients with previously treated wild-type KRAS mCRC. Accordingly, this regimen can be an additional treatment option for second-line chemotherapy in wild-type KRAS mCRC.
BACKGROUND:Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC. METHODS: Main inclusion criteria were patients with wild-type KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/kg) and irinotecan (100 mg/m(2)) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was the feasibility of the therapy. The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 36 patients received protocol treatment in eight centers. Of these, 23 patients (63.9 %) completed protocol treatment, demonstrating achievement of the primary endpoint. The most frequent grade 3/4 toxicities were diarrhea (16.7 %), acne-like rash (13.9 %), and neutropenia (11.1 %). The overall RR was 33.3 % (12/36). Of these patients, five underwent conversion surgery. Median PFS and OS were 9.5 months (95 % CI 3.5-15.4 months) and 20.1 months (95 % CI 16.7-23.2 months), respectively. CONCLUSION: IRIS plus panitumumab has an acceptable toxicity profile and a promising efficacy in patients with previously treated wild-type KRAS mCRC. Accordingly, this regimen can be an additional treatment option for second-line chemotherapy in wild-type KRAS mCRC.