title: Risk factors for severe adverse effects and treatment-related deaths in Japanese patients treated with irinotecan-based chemotherapy: a postmarketing survey.
abstract: OBJECTIVE
  This analysis was conducted to clarify risk factors for severe adverse effects and treatment-related deaths reported during a postmarketing survey of irinotecan.
  
  
  METHODS
  The survey covered all patients treated with irinotecan in Japan between April 1995 and January 2000. The patient background data and adverse drug reactions were collected through case report forms. Univariate and multivariate logistic regression analyses including 14 explanatory variables were performed to determine the risk factors for grade 3-4 leukopenia, thrombocytopenia and diarrhea for all patients and subgroups with five major cancers. Treatment-related deaths were also analyzed.
  
  
  RESULTS
  Case report forms of 13 935 patients (94.1% of 14 802 patients registered) treated with irinotecan-based chemotherapy were collected. Major grade 3-4 adverse drug reactions were leukopenia (34.8%), thrombocytopenia (12.4%) and diarrhea (10.1%). Multivariate analysis revealed that the risk factors (odds ratio ≥1.5) common for all these three adverse drug reactions were performance status (≥3), infection and renal dysfunction before starting irinotecan therapy. Additionally, the risk factors for leukopenia were being female and prior radiotherapy, those for thrombocytopenia were age (≥65 years), while those for diarrhea were pleural effusion and watery stool. The risk factors in each cancer were also identified. The incidence of treatment-related death was 1.3% (176). Myelosuppression-related deaths accounted for 70% and interstitial lung disease for 11% of all treatment-related deaths. Being male, age, performance status ≥3, massive ascites and infection and renal dysfunction were identified as risk factors for treatment-related death.
  
  
  CONCLUSIONS
  To ensure the safety of irinotecan therapy, it is important to select appropriate patients by considering the risk factors.
authors.affiliation: Post-Marketing Studies Management Department, Daiichi Sankyo Company Limited, 3-5-1 Nihonbashi-honcho, Chuo-ku, Tokyo 105-8426, Japan. shiozawa.tomoo.fb@daiichisankyo.co.jp
authors.forename: Tomoo
authors.initials: T
authors.lastname: Shiozawa
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Tadokoro
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Fujiki
authors.forename: Koji
authors.initials: K
authors.lastname: Fujino
authors.forename: Koji
authors.initials: K
authors.lastname: Kakihata
authors.forename: Shuji
authors.initials: S
authors.lastname: Masatani
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.forename: Akihiko
authors.initials: A
authors.lastname: Gemma
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D044466:Asian People / Q000706:statistics & numerical data; D001943:Breast Neoplasms / Q000188:drug therapy; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy; D003643:Death; D003967:Diarrhea / Q000139:chemically induced / Q000453:epidemiology; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D007564:Japan / Q000453:epidemiology; D007970:Leukopenia / Q000139:chemically induced / Q000453:epidemiology; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011358:Product Surveillance, Postmarketing; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D012878:Skin Neoplasms / Q000188:drug therapy; D013274:Stomach Neoplasms / Q000188:drug therapy; D013921:Thrombocytopenia / Q000139:chemically induced / Q000453:epidemiology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000077146:Irinotecan; D002166:Camptothecin
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