A phase I/II study of docetaxel in combination with doxorubicin HCI liposome injection in advanced androgen-independent prostate cancer

Abstract

14588 Background: There is no cure for men with AIPC. Recently two landmark studies demonstrated an improvement in survival for men with AIPC treated with docetaxel based chemotherapy. Doxorubicin is a very active agent against AIPC. Doxil is liposome-encapsulated doxorubicin with less toxicity. Methods: Objectives are to evaluate the efficacy and safety of DoxTax. A phase I dose escalation study was performed. Three cohorts according to the following dose escalation schedule were formed. In the absence of DLT, level 3 was the recommended dose for the phase II study. Response was assessed by size of measurable and non-measurable lesions (RECIST JNCI.2000), and PSA levels (JCO.1999). Toxicity was graded by the NCI CTCAE. Results: Eleven subjects with AIPC were enrolled and evaluated for toxicity and response. Total number of cycles administered: 59, median of 5.5 cycles/patient. Patient characteristics: Median age 67 years (53–81); prior hormonal manipulations 2 (1–2); prior chemotherapy 1 (0–2); ECOG performance status 1 (1–2); and median PSA 78 ng/ml (8.73–783). Objective response: Out of 11 subjects, four men (36%) achieved a reduction in PSA of > 50%, while one (9%) achieved a >80% PSA reduction, for an overall PSA response of 45%. Seven patients had measurable lesions. Using RECIST criteria, five of seven subjects maintained (SD). Palliative response: Nine subjects (82%) improved their ECOG performance status. Additionally, 8 men (73%) had decreased level of pain. Toxicity: No dose limiting toxicity occurred. One patient had grade 3 generalized weakness related to disease progression. Grade 1–2 adverse events were not related to the dose and included: 64% fatigue, 45% anemia, 18% neutropenia, alopecia, anorexia, vomiting, 9% each for nausea, thrombocytopenia, weakness, hand/foot, and neuropathy. Conclusions: DoxTax is a well-tolerated, easy to administer and effective therapy for patients with metastatic AIPC. Accrual to the phase II trial is ongoing. [Table: see text] [Table: see text]