title: 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.
abstract: 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.
  
  
  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/m2on 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 physician-based 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).
  
  
  CONCLUSIONS
  A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy.
authors.affiliation: Department of Digestive Surgery, Kawasaki Medical School Hospital.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tsuruta
authors.affiliation: Department of Surgery.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Medical Oncology, Okayama Rosai Hospital, Okayama.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tanioka
authors.affiliation: Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe; Department of Clinical Oncology, Faculty of Medicine, Kagawa University Hospital, Kagawa.
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Department of Medicine, Okayama Saiseikai General Hospital, Okayama.
authors.forename: Michio
authors.initials: M
authors.lastname: Inukai
authors.affiliation: Department of Surgery, Kagawa Prefectural Central Hospital, Takamatsu.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Yamakawa
authors.affiliation: Department of General Surgery, Kawasaki Medical School, Okayama.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yamatsuji
authors.affiliation: Department of Surgery, Hiroshima City Asa Hospital, Hiroshima.
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoshimitsu
authors.affiliation: Department of Surgery, National Hospital Organization Higashihirosima Medical Center, Higashihiroshima.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Toyota
authors.affiliation: Department of Surgery, Kurashiki Medical Center.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Yamano
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagasaka
authors.affiliation: Department of Surgery, Hiroshima City Hospital, Hiroshima, Japan.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Okajima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D003082:Colectomy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000187:drug effects; D009367:Neoplasm Staging; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000503:physiopathology; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology; D011446:Prospective Studies; D012307:Risk Factors; D011984:Sensory Receptor Cells / Q000187:drug effects; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil
keywords: Patient Neurotoxicity Questionnaire; adjuvant chemotherapy; oxaliplatin; peripheral neurotoxicity