Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study

Drug Design, Development and Therapy Dovepress open access to scientific and medical research Original Research Drug Design, Development and Therapy downloaded from https://www.dovepress.com/ by 110.78.154.236 on 13-Jul-2020 For personal use only. Open Access Full Text Article Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study This article was published in the following Dove Press journal: Drug Design, Development and Therapy 23 November 2016 Number of times this article has been viewed Atsushi Tsuruta, 1,* Kazuki Yamashita, 2,* Hiroaki Tanioka, 3 Akihito Tsuji, 4,5 Michio Inukai, 6 Toshiki Yamakawa, 7 Tomoki Yamatsuji, 8 Masanori Yoshimitsu, 9 Kazuhiro Toyota, 10 Taketoshi Yamano, 11 Takeshi Nagasaka, 12 Masazumi Okajima 13 On behalf of the Japan Southwest Oncology Group (JSWOG) Department of Digestive Surgery, Kawasaki Medical School Hospital, 2Department of Surgery, 3Department of Medical Oncology, Okayama Rosai Hospital, Okayama, 4 Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe, 5 Department of Clinical Oncology, Faculty of Medicine, Kagawa University Hospital, Kagawa, 6 Department of Medicine, Okayama Saiseikai General Hospital, Okayama, 7Department of Surgery, Kagawa Prefectural Central Hospital, Takamatsu, 8Department of General Surgery, Kawasaki Medical School, Okayama, 9 Department of Surgery, Hiroshima City Asa Hospital, Hiroshima, 10Department of Surgery, National Hospital Organization Higashihirosima Medical Center, Higashihiroshima, 11 Department of Surgery, Kurashiki Medical Center, 12Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 13Department of Surgery, Hiroshima City Hospital, Hiroshima, Japan 1 Background: Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients and methods: Patients with completely resected stage III and high-risk stage II CRC aged 20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m2 on days 1–14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physicianbased Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. Results: Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C–E) and CTCAE (grade 2–4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). Conclusion: A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatinbased regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy. Keywords: oxaliplatin, peripheral neurotoxicity, adjuvant chemotherapy, Patient Neurotoxicity Questionnaire *These authors contributed equally to this work Correspondence: Atsushi Tsuruta Department of Digestive Surgery, Kawasaki Medical School Hospital, Matsushima 577, Kurashiki, Okayama 701-0192, Japan Tel +81 86 462 1111 Fax +81 86 462 1199 Email Colorectal cancer (CRC) is the third leading cause of cancer death in both male and female patients worldwide.1,2 Stage IV cancer has a poor prognosis,3 but patients with stage III colon cancer who undergo radical surgery and standard adjuvant chemotherapy demonstrate a much better prognosis than those with stage IV cancer. 3827 submit your manuscript | www.dovepress.com Drug Design, Development and Therapy 2016:10 3827–3835 Dovepress © 2016 Tsuruta et al. This work is published and licensed by Dove Medical Press Limited. 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Tsuruta et al Standard adjuvant chemotherapy for stage III colon cancer involves 6 months of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) in National Comprehensive Cancer Network guidelines.4 On the other hand, the 2014 Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines for the treatment of CRC recommend the following adjuvant regimens: 6 months 5-fluorouracil (5FU) and leucovorin (LV), tegafur/uracil + LV, capecitabine, FOLFOX, and CAPOX.5 The Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer study (MOSAIC) demonstrated that 6 months of adjuvant FOLFOX treatment was associated with a significant increase in 6-year overall survival in patients with stage III colon cancer compared with LV5FU2 treatment.6,7 The National Surgical Adjuvant Breast and Bowel Project C-07 trials (NSABP C-07) also showed that adding oxaliplatin to 5FU significantly increased disease-free survival (DFS) in stage II and III colon cancer.8 The NO16968 (XELOX in Adjuvant Colon Cancer Treatment) study (XELOXA) demonstrated a statistically significant difference in 3-year DFS using CAPOX in the adjuvant treatment of stage III colon cancer.9 The established administration period of adjuvant chemotherapy is 6 months based on the publication of two Phase III stu (...truncated)