Takaoka Toshi, Kimura Tetsuo, Shimoyama Rai, Kawamoto Shunji, Sakamoto Kazuki, Goda Fuminori, Miyamoto Hiroshi, Negoro Yuji, Tsuji Akihito, Yoshizaki Koji, Goji Takahiro, Kitamura Shinji, Yano Hiromi, Okamoto Koichi, Kimura Masako, Okahisa Toshiya, Muguruma Naoki, Niitsu Yoshiro, Takayama Tetsuji
Department of Gastroenterology and Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
Department of Surgery, Shonan Kamakura General Hospital, 1370-1, Okamoto, Kamakura, Kanagawa, 247-8533, Japan.
Cancer Chemother Pharmacol. 2016 Aug;78(2):397-403. doi: 10.1007/s00280-016-3096-5. Epub 2016 Jun 24.
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.
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).
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.
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.
伊立替康联合S-1（IRIS）是唯一一种据报道不劣于FOLFIRI且在转移性结直肠癌（mCRC）患者临床实践中广泛应用的基于口服氟嘧啶的方案。然而，IRIS联合抗表皮生长因子受体（EGFR）药物的联合方案此前尚未得到评估。本研究旨在探讨IRIS联合帕尼单抗作为野生型KRAS mCRC二线治疗的可行性和疗效。
主要纳入标准为对一种先前用于mCRC的化疗方案难治的野生型KRAS mCRC患者、东部肿瘤协作组（ECOG）体能状态（PS）为0 - 2且年龄≥20岁。患者在第1天和第15天接受帕尼单抗（6 mg/kg）和伊立替康（100 mg/m²），并接受S-1（根据体表面积40 - 60 mg）每日两次，共2周，每4周重复一次。主要终点是治疗的可行性。次要终点是缓解率（RR）、无进展生存期（PFS）和总生存期（OS）。
共有36例患者在8个中心接受了方案治疗。其中，23例患者（63.9%）完成了方案治疗，表明达到了主要终点。最常见的3/4级毒性反应为腹泻（16.7%）、痤疮样皮疹（13.9%）和中性粒细胞减少（11.1%）。总体RR为33.3%（12/36）。这些患者中，5例接受了转化手术。中位PFS和OS分别为9.5个月（95%置信区间3.5 - 15.4个月）和20.1个月（95%置信区间16.7 - 23.2个月）。
IRIS联合帕尼单抗在先前治疗的野生型KRAS mCRC患者中具有可接受的毒性特征和有前景的疗效。因此，该方案可作为野生型KRAS mCRC二线化疗的一种额外治疗选择。
