ABSTRACT
BACKGROUND: We investigated the activity of lenalidomide, which has antiangiogenic, antineoplastic, and immunomodulatory properties, in chemotherapy-naive, castration-resistant prostate cancer (CRPC) patients. PATIENTS: Patients received 25 mg/d lenalidomide for 21 days in 28-day cycles, until disease progression or unacceptable toxicity developed. Endpoints included overall response rate and clinical benefit (overall response + stable disease), toxicity, time to radiographic progression, and time to prostate-specific antigen (PSA) progression, overall survival, and quality of life. RESULTS: Thirty-two patients were enrolled in the study; of these, 77% (n = 25) had Gleason scores ≥ 7. The median age was 74 years (58-89 y), the median PSA level was 66 ng/mL (2-919 ng/mL), and 5 of 32 patients (17%) had liver or lung involvement. The median number of lenalidomide cycles was 3 (1-16 cycles). Stable disease was seen in 20 patients, for a clinical benefit rate of 63%. The median time to radiographic progression was 4 months (2-16 mo); the median overall survival was 20 months. Of 27 PSA-evaluable patients, 13 (48%) had a decline in PSA level; 3 (11%) had > 50% PSA decrease; the median time to PSA progression was 3 months (2-9 mo). Grade 3/4 hematologic toxicities were the most common adverse events without adverse impact on quality of life. Serious adverse events occurred in 14 patients (44%), including 1 patient (3%) with a rash definitely related to lenalidomide. CONCLUSION: Lenalidomide monotherapy demonstrates modest activity in chemotherapy-naive CRPC.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Thalidomide/analogs & derivatives , Aged , Aged, 80 and over , Angiogenesis Inhibitors/adverse effects , Disease Progression , Disease-Free Survival , Humans , Lenalidomide , Male , Middle Aged , Neoplasm Grading , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/mortality , Quality of Life , Surveys and Questionnaires , Thalidomide/adverse effects , Thalidomide/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVES: To investigate the efficacy and toxicity of single-agent erlotinib in chemotherapy-naive castration-resistant prostate cancer. METHODS: Eligible patients received erlotinib at 150 mg daily until disease progression. Toxicity was assessed every 2 weeks and responses every 8 weeks. Primary end point was assessing the overall clinical benefit measured as the sum of stable disease, partial response, and complete response. Secondary end points included time to disease progression, overall survival, and toxicity using the National Cancer Institute Common Toxicity Criteria version 3.0. RESULTS: A total of 29 patients were enrolled in this study. Median age was 77 and median prostate-specific antigen was 66.3 ng/mL. Of 22 evaluable patients, 2 met the criteria for partial response and 5 demonstrated stable disease for an overall clinical benefit of 31%. PSA-doubling time improved in all responding patients to a median of 6 months from 3 months before entry into the study. One patient remained in study at 28 months, and 2 had > 50% decrease in their serum PSA level. Median time to disease progression was 2 months, but at 12 months, 9% of patients were progression-free. Median overall survival was 16.3 months, with 1- and 2-year survival rates of 58% and 27%, respectively. Erlotinib was well tolerated, with only 2 patients requiring dose reductions. Adverse events were as expected with grade 3 or 4 diarrhea, fatigue, and rash occurring in 10%, 6%, and 6% of patients, respectively. CONCLUSIONS: Erlotinib has moderate activity in chemotherapy-naive castration-resistant prostate cancer, with some patients showing biochemical response. Future studies investigating this agent in combination are warranted. (This trial was registered at http://NCI.gov, NCT00272038).
