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)

J Clin Oncol. 2011 Mar 10;29(8):957-62. doi: 10.1200/JCO.2009.26.4655. Epub 2011 Jan 31.

Abstract

Purpose: 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.

Patients and 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).

Conclusion: 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carboplatin / adverse effects
  • Carboplatin / therapeutic use*
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Europe
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Recurrence, Local*
  • Neoplasm Staging
  • Orchiectomy*
  • Proportional Hazards Models
  • Prospective Studies
  • Radiation Dosage
  • Radiotherapy, Adjuvant
  • Risk Assessment
  • Risk Factors
  • Seminoma / drug therapy
  • Seminoma / mortality
  • Seminoma / pathology
  • Seminoma / radiotherapy
  • Seminoma / therapy*
  • Testicular Neoplasms / drug therapy
  • Testicular Neoplasms / mortality
  • Testicular Neoplasms / pathology
  • Testicular Neoplasms / radiotherapy
  • Testicular Neoplasms / therapy*
  • Time Factors
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Carboplatin

Associated data

  • ISRCTN/ISRCTN27163214