Chlorambucil and lomustine (CL56) in absolute hormone refractory prostate cancer: re-induction of endocrine sensitivity an unexpected finding

The management of androgen independent prostate cancer is increasingly disputed. Diethylstilbestrol and steroids have useful second-line activity in its management. The value of chemotherapy still remains contentious. This paper reports a phase 2 study of two orally active chemotherapy drugs in patients who are absolutely hormone refractory having failed primary androgen blockade and combined oestrogens and corticosteroids. In total, 37 patients who were biochemically castrate with absolute hormone refractory prostate cancer and performance status of 0–3 were enrolled. Therapy consisted of chlorambucil 1 mg kg(−1) given as 6 mg a day until the total dose was reached and lomustine 2 mg kg(−1) given every 56 days (CL56). During this time all hormone therapy was stopped. One patient normalised his PSA with a further two having a greater than 50% decline leading to an objective response rate of 10%. The median time to progression was 3.6 months with an overall survival of 7.1 months. The median survival of this group of patients from first becoming androgen independent was 23.5 months. Eight of 17 (47%) patients who were subsequently re-challenged with hormonal therapy following failure of chemotherapy had a further PSA reduction, three (17%) of which were >50%. The median progression-free interval for the eight patients was 4 months. In conclusion, CL56 has a low objective response rate in the management of absolute hormone refractory prostate cancer. Toxicity was mild. Re-induction of hormone sensitivity following failure of chemotherapy was an unexpected finding that requires further study.