22 year phase 1/2 study of single agent carboplatin in metastatic seminoma: Potential for acceleration by a new surrogate end point, 72 hr PET scan response?

Abstract

14565 Background: That metastatic seminoma may be more chemo-curable than non-seminoma was first suggested by Samuels (1980 Proc ASCO 21 abst 415) 4 of 5 patients durable CR to single agent cisplatin and by Oliver (1984 Proc ASCO 3. Abst 636) 9 of 10 durable responses. Carboplatin proved less effective and in randomised trials involving 361 patients relapse free survival was 72% with Carbo and 92% with cisplatin-based combination. Prompted by successful dose escalation of carboplatin in ovarian cancer, the initial phase 1 study that preceded the UK randomised trial was reopened and dosage escalated to AUC 8 and then 10. This abstract updates this study and provides more prolonged follow up of the previous reported cases. Methods: Initially patients received Carboplatin 450 mg/m2 (1983–7) and then AUC 7 (88–94), 8 (95–6) and 10 (97–06). The treatment was repeated q21 when possible and if delayed because of toxicity blood counts were repeated every 24 hours. Results: 60 metastatic seminoma patients have been treated between 1983 and 2006. 79%/95% of 19 receiving 450 mg/m2, 88%/94% of 17 receiving AUC 7 or 8 and 92%/100% of 24 receiving AUC 10 are progression free/alive. Overall 58 (97%) are alive and with 28 patients followed more than 10 years there have been no relapses after 26 months. Mild and rapidly recovering (med 14 d) transaminitis in 64% of AUC × 10 (med 93 range 51–541) suggests this may be the upper limit for safe use. As a pilot study 5 seminomas receiving AUC × 10 and 6 non-seminomas receiving BEP had PET scan before and at 72 hours after treatment. The only patient failing to respond substantially was a seminoma who showed increased PET activity on AUC × 10 but achieved complete remission of PET activity after one course of BEP. Conclusion: This data confirms the need for more studies of single agent platinum analogues in seminomas and reinforces the view that it may be preferable to radiotherapy for patients electing adjuvant treatment. With increasing attention being paid to late events, minimizing treatment toxicity and finding a fast track approach to proving safety is an increasing need. The data presented demonstrates the potential of early PET scan as a surrogate for response and could have accelerated the phase 1/2 study reported. No significant financial relationships to disclose.