20 year phase 1/2 study of single agent carboplatin in metastatic seminoma: Could it have been accelerated by 72 hr PET scan response?

Abstract

4763 Background: Samuels et al (1980 Proc ASCO 21 abst 415) observed 4 of 5 bulky seminomas achieved durable CR to single agent cisplatin and Oliver 1984 Proc ASCO 3. Abst 636) reported 9 of 10 durable responses. Carboplatin proved less effective and in randomised trials involving 361 patients relapse free survival was 71% with Carbo and 91% 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 escalation to AUC 8 and then 10 was undertaken. This abstract updates this study with more prolonged follow up of the previous cases and new information on the higher dosages. Methods: Initially patients received 450mg/m2 and subsequently the dose was increased to AUC 7, 8 and 10. The treatment was repeated q21 when possible and if delayed because of toxicity blood counts were repeated every 24 hours. Results: A total of 49 metastatic seminoma patients have been treated between 1983 and 2003. 79% of 19 receiving 450mg/m2, 88% of 17 receiving AUC 7 or 8 and 92% of 12 receiving AUC 10 are relapse free. As a pilot study 7 patients with a variety of metastatic germ cell cancers have had PET scan performed before and at 72 hours after treatment. 3 achieved CR, 3 had greater than 40% response and 1 after progressing after single agent carboplatin was in complete remission after one course of BEP. Conclusion: With late events increasingly a problem with more prolonged follow up of testis cancer, 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 marker to facilitate assessment of response and could have accelerated the phase 1/2 study reported. No significant financial relationships to disclose.