A randomized comparison of single agent carboplatin with radiotherapy in the adjuvant treatment of stage I seminoma of the testis following orchiectomy: MRC TE19/EORTC 30982

Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 7 de junio del 2004

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This presentation discusses off-label use of carboplatin in the treatment of seminoma.

Presenter: R.T. Oliver
Presenter's Affiliation: Medical Research Counsel, England
Type of Session: Scientific

Background

  • Adjuvant radiation therapy (RT) is an effective treatment for stage I seminoma following orchiectomy; however, it is associated with an increased long-term risk of secondary cancers and cardiac disease of ~20%
  • Post-operative surveillance is a reasonable option, but long-term surveillance is often very difficult to achieve due to the intensive nature of the radiographic and clinical follow-up
  • Previous trials have shown equally effective results treatment with reduced dose and volumes with RT
  • Pilot studies have shown that a single dose of carboplatin may be as effective as RT for stage I seminoma
  • This randomized, prospective study was designed to detect a difference in rates of relapse between RT and a single dose of carboplatin for stage I seminoma

Materials and Methods

  • Patients with stage I seminoma were randomized to receive either adjuvant RT or adjuvant carboplatin following radical orchiectomy
  • Radiation consisted of treatment to either the paraaortic (PA) lymph nodes  or a "dogleg" (DL) field consisting of the PA nodes and the ipsilateral inguinal lymph nodes.
  • A secondary randomization was carried out in the RT arm between a total dose of 30 Gy in 15 fractions vs. 20 Gy in 10 fractions.  The results of this randomization are not included in this report
  • Chemotherapy consisted of one cycle of carboplatin (AUC = 7) given after radical orchiectomy
  • The study was designed as a non-equivalence study to detect a difference in relapses of 3% with 90% confidence using 1200 patients

Results

  • 1477 patients were randomized in a 3:5 ratio for carboplatin (n=573) and RT (n=904)
  • Median follow-up was 4 years
  • Patient characteristics were well balanced between groups with a mean age of 38 years
  • Of the patients who received RT, 13% were treated with a DL field and 87% were treated to the PA lymph nodes only
  • 3-year relapse-free survival (RFS) for the RT vs. carboplatin groups was 96.6% vs. 95.4% with a hazard ratio (HR) of 1.39 (90% CI 0.92-2.11)
  • Patterns of relapsed differed between the two group: the PA lymph nodes only were the site of relapse for 70% of patients relapsing with carboplatin vs. 7% of patients relapsing with RT
  • A higher rate of grade 3/4 leukopenia was seen in the carboplatin group (1.2% vs. 0.5%)
  • A higher rate of grade 3/4 thrombocytopenia was seen in the carboplatin group (9% vs. 0%, p<0.001)
  • A higher rate of dyspepsia was seen in the RT group (8% vs. 17%, p<0.001) 
  • At 12 weeks after treatment, patients in the carboplatin group experienced lower rates of lethargy, nausea, and inability to work
  • Second germ cell tumors (GCT) have been seen in 2 patient treated with carboplatin vs. 10 patients treated with RT
  • Second non-GCTs have been seen in 3 patients treated with carboplatin vs. 4 patients treated with RT
  • No treatment related deaths were reported in either group

Author's Conclusions

  • An absolute increase in relapse of 3% with adjuvant carboplatin can be reliably excluded
  • Carboplatin results in lower rates of lethargy, nausea, and inability to work 12 weeks after treatment
  • Further follow-up to detect late relapses
  • 20 year follow-up is needed to assess long-term toxicities of carboplatin

Clinical/Scientific Implications

The optimal treatment of patients with stage I seminomas is unclear.  Several strategies have been employed including observation, RT, and single dose carboplatin.  Observation is a reasonable option in compliant patients, but it requires a large amount of long-term follow-up imaging which is often difficult to perform.  In addition, a significant proportion of patients on observation will recur and ultimately require treatment.  While RT has been the standard treatment for most patients with stage I seminoma, it has been associated with significant late toxicities including increased risk of secondary malignancies and cardiac deaths.  Use of carboplatin has been attractive because it potentially has less toxicity than RT.  In this study, the use of adjuvant carboplatin does not appear to increase the risk of relapse when compared to RT.  The use of adjuvant carboplatin rather than RT may result in improved overall outcomes; however, the long term toxicities of carboplatin have not been reported, while 20-year follow-up for RT is available.  Adjuvant carboplatin appears to be a viable alternative to RT for these patients with the important caveat that the long-term outcomes for these patients is not known and data for this will not be available for many years.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.



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