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Myths and Facts on Adjuvant Carboplatin for Stage I Seminoma

Department of Medical Oncology, Hospital Universitario La Fe, Valencia, Spain

José R. Germà

Department of Medical Oncology, Idibell-Institut Catalá d'Oncologia Duran i Reynals, Barcelona, Spain

To the Editor:

We appreciate the interest of Loehrer and Bosl in our Spanish Germ Cell Cancer Group (SGCCG) study¹, which coincides with their editorial² on the concept of risk-adapted therapy as an appropriate area of investigation for patients with clinical stage I seminoma. We also agree that longer follow-up of our series is needed and confirmatory studies should be performed before integrating the risk-adapted approach into clinical practice.¹ However, some of the inaccuracies that have been raised in their dissection of our article merit attention. Adjuvant carboplatin can no longer be considered an unproven treatment, because a large (not cited in their editorial) randomized trial has demonstrated its equivalence with radiation in terms of efficacy and less toxic effects.³ No such comparison has ever been made against surveillance, which is a widely accepted alternative to radiotherapy. We do not agree that carboplatin is an inferior drug in the adjuvant setting because of two main arguments. Firstly, in Bokemeyer's review⁴ carboplatin alone was compared to cisplatin-based polichemotherapy in metastatic seminoma, and this drug was administered using a fixed dose of 400 mgs/m² instead of employing Calvert's formula with an area under the curve of 7, as we and Oliver et al³ did. Secondly, cumulative experience shows that carboplatin is effective enough in the adjuvant setting, with more than 800 patients so treated, a consistent relapse rate lower than 5%, and an overall 5-year survival of 100%.^3,5 This relapse rate is in the range of that observed after radiation, recurrences are mostly retroperitoneal, and effective salvage is almost invariably obtained with four courses of cisplatin-based chemotherapy. Furthermore, an adequate follow-up (median, 72 months) in this pooled analysis precludes the chance of significant late adverse effects or late relapses, while showing a significant reduction in the probability of second germ-cell tumors.

In this context, it is conceptually difficult to continue recommending systematic (indiscriminate) prophylactic radiation because more than 80% of these patients are cured with orchiectomy alone and the late hazards of radiotherapy (mainly second malignancies) are well known. Moreover, although predictive factors for relapse should be refined, a truly high-risk group can be defined as one in which surveillance seems inadequate: those patients with tumors greater than 4 cm and rete testis invasion have a predicted relapse rate of 31.5%⁶; not 68.5%, as stated by Loehrer and Bosl. In fact, our third ongoing SGCCG study restricts adjuvant carboplatin to this 15% to 20% of the population, reserving surveillance for the remainder of patients. Finally, we agree that standard recommendations need formal randomized comparison. Therefore, after the confirmed knowledge from a well-designed phase III trial³ that one cycle of carboplatin is equivalent and less toxic than prophylactic radiotherapy for stage I seminoma, a risk-adapted approach seems to be the next step to spare unnecessary toxicity in as many patients as possible. While a large randomized trial is designed, this dual treatment policy with a low relapse rate and a 100% cure rate seems to have enough entity to be discussed with clinical stage I seminoma patients as an alternative to more interventionist approaches.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Aparicio J, Germà JR, García del Muro X, et al: Risk-adapted management for patients with clinical stage I seminoma: The second Spanish Germ Cell Cancer Cooperative Group study. J Clin Oncol 23:8717-8723, 2005[Abstract/Free Full Text]

2. Loehrer PJ Sr, Bosl GJ. Carboplatin for stage I seminoma and the sword of Damocles. J Clin Oncol 23:8566-8569, 2005[Free Full Text]

3. Oliver RTD, Mason MD, Mead GM, et al: Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: A randomised trial. Lancet 366:293-300, 2005[CrossRef][Medline]

4. Bokemeyer C, Kollmannsberger C, Stenning S, et al: Metastatic seminoma treated with either single agent carboplatin or cisplatin-based combination chemotherapy: A pooled analysis of two randomized trials. Br J Cancer 91:683-687, 2004[Medline]

5. Oliver T, Dieckmann KP, Steiner H, et al: Pooled analysis of phase 2 reports of 2 v 1 course of carboplatin as adjuvant for stage 1 seminoma. J Clin Oncol 23:395s, 2005 (abstr 4572)

6. Warde P, Specht L, Horwich A, et al: Prognostic factors for relapse in stage I seminoma managed by surveillance: A pooled analysis. J Clin Oncol 20:4448-4452, 2002[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Aparicio, J. Articles by Germà, J. R. Search for Related Content PubMed PubMed Citation Articles by Aparicio, J. Articles by Germà, J. R. Social Bookmarking                            What's this?