Objective: In hormone refractory prostatic carcinoma (HRPCa), the majority of patients have bone metastases only, which are by definition non-measurable. This makes objective evaluation of chemotherapeutic agents difficult. Prostate specific antigen (PSA) as a dynamic model was analyzed as potential auxiliary end point in HRPCa.
Methods: In the framework of a master protocol, the Swiss Group for Clinical Cancer Research (SAKK) is evaluating cytotoxic drugs in HRPCa since 1991. These prospective phase II trials include uniform requirements with regard to response, toxicity and quality of life. From the entire pool of patients, 40 with bidimensionally measurable metastases (lymph nodes, visceral organs) could be identified. PSA doubling time was calculated in patients with a rising PSA during therapy.
Results: Objective best response to any given chemotherapeutic agent was: partial remission (PR) in six patients (15%), stable disease (SD) in 13 (32%) and progressive disease (PD) in 21 (53%). PSA remained stable or decreased in four of six patients with PR (67%), seven of 13 with SD (54%) but only in four of 21 with PD (19%) (Cochran-Armitage test for trend; p=0.015). The median PSA doubling time for patients with a rising PSA was 238 days in PR and 224 days in SD, compared to 113 days in PD (Wilcoxon test; p=0.002).
Conclusions: PSA doubling time is a potential auxiliary end point in the evaluation of cytotoxic drugs in HRPCa. Thus, also patients with non-measurable (bone) metastases could be included in analysis of response.