title: Phase II study of reintroduction of oxaliplatin for advanced colorectal cancer in patients previously treated with oxaliplatin and irinotecan: RE-OPEN study.
abstract: BACKGROUND
  The effectiveness of reintroducing oxaliplatin in patients with metastatic colorectal cancer refractory to standard chemotherapy has not been verified. We performed a single-arm, open-label, Phase II study to evaluate the safety and efficacy of reintroducing oxaliplatin.
  
  
  METHODS
  Eligible patients had received prior chemotherapy including oxaliplatin and irinotecan that achieved a response or stable disease followed by confirmed disease progression ≥6 months previously during prior oxaliplatin-based therapy. The primary endpoint was the disease control rate (DCR) after 12 weeks of treatment starting. The DCR was defined as the sum of patients with complete response, partial response, and stable disease.
  
  
  RESULTS
  Thirty-three patients were enrolled. The median age was 62 (range: 35-77) years and the male/female ratio was 19/14. Eastern Cooperative Oncology Group performance status was 0 in 84.8%. Fourteen primary tumors were in the colon and 19 were in the rectum. All patients received modified FOLFOX6 as the protocol treatment. After 12 weeks of treatment starting, the DCR was 39.4% (95% confidence interval 21.8-57.0) and the response rate (complete response and partial response) was 6.1%. The median number of chemotherapy cycles was five and the median total dose of oxaliplatin was 425 mg/m(2). Median progression-free survival time was 98 days and median overall survival was 300 days. The incidence of grade ≥1 and grade ≥3 allergic reactions was 28.1% and 3.1%, respectively. The incidence of grade ≥1 and grade ≥3 peripheral sensory neuropathy was 53.1% and 0%, respectively. There were no other severe adverse events and no treatment-related deaths.
  
  
  CONCLUSIONS
  Reintroducing oxaliplatin can be both safe and effective. This may be a salvage option for patients with metastatic colorectal cancer who achieved a response or stable disease with prior oxaliplatin-based therapy followed by disease progression ≥6 months previously during prior oxaliplatin-based therapy.
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Suenaga
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsusaka
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinozaki
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ozaka
authors.affiliation: Department of Gastroenterology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D004342:Drug Hypersensitivity / Q000453:epidemiology; D023381:Endpoint Determination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000453:epidemiology; D011446:Prospective Studies; D016879:Salvage Therapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: FOLFOX; advanced colorectal cancer; oxaliplatin; reintroduction; salvage-line