title: Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors.
abstract: OBJECTIVE
  No increase in second tumor incidence was found in a previous analysis of women treated with chemotherapy for gestational trophoblastic tumors (GTT). More patient years at risk enabled a further analysis of the risk of second tumors to be performed in the 1,377 women treated in this until up to 1990.
  
  
  METHODS
  Health questionnaires were returned on 93.3% of patients who successfully completed chemotherapy and were living in the United Kingdom. The remainder were flagged for death or developing further cancers by the Office of Population Census and Surveys and by the Thames Cancer Registry. Incidence density analysis was performed based on 15,279 person-years of observation available. Standardized incidence ratio (SIR) was used to estimate the relative risk (RR) of second tumors associated with the treatment. To calculate the expected number, the actual incidence rates observed by the Thames Cancer Registry during the same calendar period of observation were used.
  
  
  RESULTS
  An overall 50% excess of risk (RR = 1.5; 95% confidence interval [CI], 1.1 to 2.1; P < .011) was observed: there were 37 second tumors, when 24.5 were expected. For specific second tumors, the risk was significantly increased for myeloid leukemia (RR = 16.6; 95% CI, 5.4 to 38.9), colon (RR = 4.6; 95% CI, 1.5 to 10.7), and breast cancer when the survival exceeded 25 years (RR = 5.8; 95% CI, 1.2 to 16.9). The risk was not significantly increased among the 554 women receiving single-agent therapy (RR = 1.3; 95% CI, 0.6 to 2.1). Leukemias only developed in patients receiving etoposide plus other cytotoxic drugs.
  
  
  CONCLUSIONS
  This study suggests that there is a slight increased risk of second tumors after sequential or combination chemotherapy for GTT. This has become apparent since the introduction of etoposide and longer follow-up.
authors.affiliation: Department of Medical Oncology, Charing Cross Hospital, London, United Kingdom. RUSTIN@MTVERN.CO.UK
authors.forename: G J
authors.initials: GJ
authors.lastname: Rustin
authors.forename: E S
authors.initials: ES
authors.lastname: Newlands
authors.forename: J M
authors.initials: JM
authors.lastname: Lutz
authors.forename: L
authors.initials: L
authors.lastname: Holden
authors.forename: K D
authors.initials: KD
authors.lastname: Bagshawe
authors.forename: J G
authors.initials: JG
authors.lastname: Hiscox
authors.forename: M
authors.initials: M
authors.lastname: Foskett
authors.forename: S
authors.initials: S
authors.lastname: Fuller
authors.forename: D
authors.initials: D
authors.lastname: Short
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D003609:Dactinomycin / Q000009:adverse effects; D005047:Etoposide / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008727:Methotrexate / Q000009:adverse effects; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000139:chemically induced* / Q000453:epidemiology*; D011247:Pregnancy; D013997:Time Factors; D014328:Trophoblastic Neoplasms / Q000188:drug therapy*; D014594:Uterine Neoplasms / Q000188:drug therapy*
chemical_list: D003609:Dactinomycin; D005047:Etoposide; D008727:Methotrexate