A143
A study of melanoma patients in Phase I clinical trials: looking beyond the established
S Frentzas, AT Brunetto, D Olmos, D Tan, C Mikropoulos, S Stapleton, U Banerji, S Kaye
Royal Marsden Hospital, London, UK
Background
Whilst early-stage melanoma has an excellent clinical outcome, metastatic disease is almost universally fatal. The median OS for patients with advanced disease is 8.1 months with an approximate 5-year survival rate of 2%. Due to the paucity of effective standard therapies, an increasing number of patients are offered entry into early clinical trials.
Method
We retrospectively analyzed baseline characteristics and clinical outcome of all melanoma patients treated in the Drug Development Unit, at our institution between May 2002 and March 2008.
Results
A total of 54 patients that enrolled into 35 different phase I trials were analyzed in the study period. 16 patients participated in more than one phase I trial and a total of 73 trial entries were analysed. The median age per patient when starting trial was 56.8 years (range:17.5-78.5) and the m/f ratio was 1.7:1. All patients had evidence of progressive disease before trial entry. The median PFS for all trials was 7.1 weeks (95% CI: 6.0-8.2 weeks) and the median OS for all patients was 7.0 months (95% CI: 5.5-8.4 months). The RR for all therapies was 4.3% and 37.1 % had SD at first radiological assessment. 10/54 patients had diagnosis of ocular melanoma. Most common agents used were histone deacetylase inhibitors (HDACi) (16.4%), viral/immune therapies (16.4%), tyrosine kinase receptors (15.1%), and heat shock protein inhibitors (HSPi)(9.6%). Novel agents that showed promising activity included HDACi and HSPi.
Conclusion
Despite low RR seen in early clinical trials, there seems to be group of patients that benefit significantly from treatment. Modern anti-neoplastic drug development for melanoma is becoming target-orientated in the hope of providing novel drugs which are more effective and less toxic. Understanding the biology of the tumours that more likely to respond to a specific therapy will help advance the selection of treatment.
