title: Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214).
abstract: OBJECTIVE
  Initial results of a randomized trial comparing carboplatin with radiotherapy (RT) as adjuvant treatment for stage I seminoma found carboplatin had a noninferior relapse-free rate (RFR) and had reduced contralateral germ cell tumors (GCTs) in the short-term. Updated results with a median follow-up of 6.5 years are now reported.
  
  
  METHODS
  Random assignment was between RT and one infusion of carboplatin dosed at 7 × (glomerular filtration rate + 25) on the basis of EDTA (n = 357) and 90% of this dose if determined on the basis of creatinine clearance (n = 202). The trial was powered to exclude a doubling in RFRs assuming a 96-97% 2-year RFR after radiotherapy (hazard ratio [HR], approximately 2.0).
  
  
  RESULTS
  Overall, 1,447 patients were randomly assigned in a 3-to-5 ratio (carboplatin, n = 573; RT, n = 904). RFRs at 5 years were 94.7% for carboplatin and 96.0% for RT (RT-C 90% CI, 0.7% to 3.5%; HR, 1.25; 90% CI, 0.83 to 1.89). One death as a result of seminoma (in RT arm) occurred. Patients receiving at least 99% of the 7 × AUC dose had a 5-year RFR of 96.1% (95% CI, 93.4% to 97.7%) compared with 92.6% (95% CI, 88.0% to 95.5%) in those who received lower doses (HR, 0.51; 95% CI, 0.24 to 1.07; P = .08). There was a clear reduction in the rate of contralateral GCTs (carboplatin, n = 2; RT, n = 15; HR, 0.22; 95% CI, 0.05 to 0.95; P = .03), and elevated pretreatment follicle-stimulating hormone (FSH) levels (> 12 IU/L) was a strong predictor (HR, 8.57; 95% CI, 1.82 to 40.38).
  
  
  CONCLUSIONS
  These updated results confirm the noninferiority of single dose carboplatin (at 7 × AUC dose) versus RT in terms of RFR and establish a statistically significant reduction in the medium term of risk of second GCT produced by this treatment.
authors.affiliation: St Bartholomews and the London Hospital, London, United Kingdom.
authors.forename: R Timothy D
authors.initials: RT
authors.lastname: Oliver
authors.forename: Graham M
authors.initials: GM
authors.lastname: Mead
authors.forename: Gordon J S
authors.initials: GJ
authors.lastname: Rustin
authors.forename: Johnathan K
authors.initials: JK
authors.lastname: Joffe
authors.forename: Nina
authors.initials: N
authors.lastname: Aass
authors.forename: Robert
authors.initials: R
authors.lastname: Coleman
authors.forename: Rhian
authors.initials: R
authors.lastname: Gabe
authors.forename: Philip
authors.initials: P
authors.lastname: Pollock
authors.forename: Sally P
authors.initials: SP
authors.lastname: Stenning
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005060:Europe; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009919:Orchiectomy; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011829:Radiation Dosage; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D012307:Risk Factors; D018239:Seminoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D013736:Testicular Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin