Clinical trialPhase 3Testicular cancer

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 · 20111,477 patients (573 carboplatin and 904 radiotherapy)

Oliver RT, Mead GM, Rustin GJ, Joffe JK, Aass N, Coleman R, et al. J Clin Oncol. 2011. 29:957-962

Study type: Clinical trial
Study name: MRC TE19/EORTC 30982
Phase: Phase 3
Design: Randomised multicentre non-inferiority trial with 3:5 allocation (carboplatin to radiotherapy)
Sample size: 1,477 patients (573 carboplatin and 904 radiotherapy)
Source: J Clin Oncol · 2011
Trial registration: NCT00003014

In plain words

In this large study, men with stage 1 seminoma who had had the testicle removed received either a single injection of the drug carboplatin or radiotherapy. After about 6 years, the chance of the cancer coming back was almost the same in both groups, but new cancer in the other testicle was seen less often with carboplatin. Those who received the full dose of carboplatin did better.

Key results

94.7% (carboplatin) vs 96.0% (radiotherapy)

5-year relapse-free rate

HR 1.25; 90% CI 0.83–1.89

2 patients (carboplatin) vs 15 patients (radiotherapy)

Contralateral germ cell tumour of the testis

HR 0.22; 95% CI 0.05–0.95; P = 0.03

96.1% (at least 99% of the 7 × AUC dose) vs 92.6% (lower dose)

5-year relapse-free rate by carboplatin dose received

HR 0.51; 95% CI 0.24–1.07; P = 0.08

1 death (in the radiotherapy arm)

Deaths from seminoma

HR 8.57

Raised pretreatment FSH (above 12 IU/L) as a predictor of contralateral tumours

95% CI 1.82–40.38

Drugs in this study:Carboplatin (Paraplatin)

Dose and schedule cards

Single-dose carboplatin AUC 7 (stage I seminoma)

Clinical stage I seminoma after radical inguinal orchidectomy, when adjuvant treatment is chosen instead of active surveillance (surveillance is preferred; adjuvant treatment is not recommended in patients without risk factors)Cycle length: Single doseOn the page “Testicular cancer” · Adjuvant treatment of stage I after orchidectomy

Drug	Dose	Route	Schedule
Carboplatin	AUC 7; dose (mg) = 7 × (GFR + 25)	IV	Day 1, once

Cycle length: Single dose
Duration: 1 dose

Dosing as in the MRC TE19/EORTC 30982 trial: GFR was measured with a radioisotope (EDTA) method, and patients whose GFR was estimated from creatinine clearance received 90% of this dose. Do not reduce the dose: patients who received at least 99% of the dose had a 5-year relapse-free rate of 96.1% vs 92.6% with a lower dose. Dosing based on calculated creatinine clearance is not equivalent and has not been validated in this setting. EAU recommendation: if adjuvant treatment is considered, one dose of carboplatin AUC 7 (strong). Calculation: carboplatin dose calculator.

On the page “Testicular cancer” · Adjuvant treatment of stage I after orchidectomy

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Single-dose carboplatin (573 patients)

One infusion of carboplatin at a dose of 7 × (GFR + 25) mg based on GFR measured by EDTA (357 patients); 90% of this dose if GFR was determined from creatinine clearance (202 patients).

2Radiotherapy (904 patients)

Radiotherapy to a para-aortic strip or dog-leg field. The radiation dose is not given in the abstracts; dose details are in the full text of the paper.

Source of the regimen details: Abstract of the initial report (Lancet 2005; PubMed 16039331) and of the mature results (J Clin Oncol 2011)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Men with stage I seminoma after orchidectomy, from 70 hospitals in 14 countries, randomised between 1996 and 2001 (according to the initial report). Other inclusion criteria are not given in the abstracts.

Endpoints

Primary endpoint: relapse-free rate (RFR). The trial was designed to exclude a doubling of the relapse rate, assuming a 2-year RFR of 96–97% after radiotherapy (HR about 2.0). Contralateral germ cell tumours of the testis were also assessed.

Safety and side effects

In the initial report, patients given carboplatin were less lethargic and less likely to take time off work. Rates of grade 3 or higher adverse events are not reported in the abstracts.

Clinical significance and place in guidelines

This trial established single-dose carboplatin AUC 7 as an alternative to adjuvant radiotherapy in stage I seminoma. The initial report (median follow-up 4 years) had already shown similar 2-year relapse-free survival (97.7% vs 96.7%) and fewer contralateral tumours with carboplatin. The EAU guideline regards active surveillance as the preferred option and, if adjuvant treatment is considered, strongly recommends one dose of carboplatin AUC 7. The importance of the full dose (measured GFR) is one of the key findings.

Limitations

This card is based on the abstracts of the initial report and the mature results. The radiotherapy dose and details of toxicity are not given in the abstracts. The 2011 abstract gives the total as 1,447, whereas the sum of the two arms (573 + 904) and the initial report give 1,477. The analysis by received dose and the role of FSH are exploratory. Active surveillance (today’s preferred option) was not compared in this trial.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.