title: Phase II trial of oral etoposide plus intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer (JCOG0503).
abstract: OBJECTIVE
  To assess the safety and efficacy of the combination of oral etoposide and intravenous irinotecan in patients with platinum-resistant and taxane-pretreated ovarian cancer.
  
  
  METHODS
  Eligible patients (age, 20-75years; platinum-free interval, ≤28weeks) with an adequate organ function received oral etoposide (50mg/m(2) once a day) from day 1 to day 21 and intravenous irinotecan (70mg/m(2)) on days 1 and 15. The regimen was repeated every 28days up to 6cycles. The primary endpoint was the response rate (RR) with a threshold of 20%. The response was evaluated according to RECIST 1.0 and Gynecologic Cancer Intergroup CA-125 Response Definition, and toxicities were evaluated according to CTCAE version 3.0. This trial was registered at UMIN-CTR as UMIN000001837.
  
  
  RESULTS
  Between April 1, 2009 and January 20, 2012, 61 patients were enrolled. Sixty patients were eligible. 1 CR and 12 PRs were confirmed; RR was 21.7% (p=0.42, the exact binomial test). PFS and OS were 4.1 and 11.9months, respectively. Major toxicities of ≥grade 3 were neutropenia (60%), anemia (36.7%), thrombocytopenia (11.7%), febrile neutropenia (18.3%), fatigue (13.3%), anorexia (11.7%), and nausea (11.7%). Three patients died from treatment related death (interstitial pneumonia, a pulmonary embolism, and DIC due to infection). Two of these patients were aged ≥65years.
  
  
  CONCLUSIONS
  Oral etoposide and intravenous irinotecan had a moderate RR but did not meet the primary endpoint. Because of toxicity, we do not recommend this regimen outside of clinical trials. In particular, when considering this regimen for elderly patients, extreme caution is advised.
authors.affiliation: Hyogo Cancer Center, Japan. Electronic address: kojmatsu@hp.pref.hyogo.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Nippon Medical School Musashikosugi Hospital, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Katsumata
authors.affiliation: JCOG Data Center, Multi-institutional Clinical Trial Support Center, National Cancer Center, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shibata
authors.affiliation: University of Tsukuba, Japan.
authors.forename: Toyomi
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Jikei University Hospital, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saitou
authors.affiliation: National Cancer Center Hospital, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Yunokawa
authors.affiliation: Tohoku University Hospital, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Takano
authors.affiliation: JCOG Data Center, Multi-institutional Clinical Trial Support Center, National Cancer Center, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Kurume University School of Medicine, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Kamura
authors.affiliation: Kyoto University Hospital, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000494:pharmacology; D055815:Young Adult
chemical_list: D001952:Bridged-Ring Compounds; D009944:Organoplatinum Compounds; D043823:Taxoids; C080625:taxane; D005047:Etoposide; D000077146:Irinotecan; D002166:Camptothecin
keywords: Combination chemotherapy; Irinotecan; Oral etoposide; Ovarian cancer; Platinum resistant; Taxane pretreated