A Multicenter Phase 2 Study on the Feasibility and Efficacy of Neoadjuvant Chemotherapy Without Radiotherapy for Locally Advanced Rectal Cancer

• Published in: Annals of surgical oncology Vol. 24; no. 12; pp. 3587 - 3595
• Main Authors: Hasegawa, Suguru, Goto, Saori, Matsumoto, Takuya, Hida, Koya, Kawada, Kenji, Matsusue, Ryo, Yamaguchi, Takashi, Nishitai, Ryuta, Manaka, Dai, Kato, Shigeru, Kadokawa, Yoshio, Yamanokuchi, Satoshi, Kawamura, Junichiro, Zaima, Masazumi, Kyogoku, Takahisa, Kanazawa, Akiyoshi, Mori, Yukiko, Kanai, Masashi, Matsumoto, Shigemi, Sakai, Yoshiharu
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.11.2017; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Cancer; Cetuximab - administration & dosage; Chemotherapy; Colorectal Cancer; Feasibility Studies; Female; Fluorouracil - administration & dosage; Follow-Up Studies; Humans; K-Ras protein; Leucovorin - administration & dosage; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Mutation; Neoadjuvant Therapy; Oncology; Organoplatinum Compounds - administration & dosage; Prognosis; Prospective Studies; Radiation therapy; Rectal Neoplasms - drug therapy; Rectal Neoplasms - pathology; Rectum; Sphincter; Surgery; Surgical Oncology; Surgical site infections; Survival Rate; Targeted cancer therapy; KRAS Status; Locally Advanced Rectal Cancer (LARC); Cetuximab; Sphincter-preserving Surgery; Bevacizumab
• ISSN: 1068-9265; 1534-4681; 1534-4681
• DOI: 10.1245/s10434-017-5967-3

Background This prospective multicenter phase 2 study aimed to evaluate the feasibility and efficacy of neoadjuvant chemotherapy (NAC) without radiotherapy for locally advanced rectal cancer (LARC). Methods Patients with LARC (cStage II and III) were included in the study. Those with cT4b tumor were excluded. Six cycles of modified FOLFOX6 (mFOLFOX6) plus either bevacizumab or cetuximab, depending on KRAS status, were administered before surgery. The primary end point of the study was the R0 resection rate. The secondary end points were adverse effect, rate of NAC completion, postoperative complications, and pathologic complete response (pCR) rate. Results The study enrolled 60 patients from eight institutions. For the study, mFOLFOX6 was administered with cetuximab to 40 patients who had wild-type KRAS and with bevacizumab to 20 patients who had KRAS mutations. The completion rate for NAC was 88.4%. Sphincter-preserving surgery was performed for 43 patients and abdominoperineal resection for 17 patients. The median operation time was 335 min, and the median blood loss was 40 g. The R0 resection rate was 98.3%, and the pCR rate was 16.7%. The overall postoperative complication rate (≥grade 2) was 21.7%. The complications included anastomotic leakage (11.6%), surgical-site infection (6.7%), and urinary dysfunction (3.3%). The patients with wild-type KRAS did not differ significantly from those with KRAS mutations in terms of response rate, postoperative complication rate, and pCR rate. Conclusion The findings show that NAC is a feasible and promising treatment option for LARC (This study is registered with UMIN-CTR, UMIN000005654).