A phase II study to evaluate the effects of docetaxel plus lycopene in advanced castrate-resistant prostate cancer.

Abstract

77 Background: Lycopene, the carotenoid responsible for the red colors seen in tomatoes, grapefruit, and other foods, has demonstrated synergism with docetaxel in prostate cancer cell culture and tumor xenograft models. This phase II study investigated the clinical activity and safety profile of docetaxel plus lycopene in advanced castrate resistant prostate cancer. Methods: Eligible patients had histologically confirmed adenocarcinoma of the prostate, two rising pre-study prostate specific antigen (PSA) values ≥ 1 ng/ml, and no prior treatment with any chemotherapy, biological therapy, or investigational drug. All patients initially received docetaxel 75mg/m2 every 21 days in combination with lycopene 30 mg orally once daily. The primary endpoint was PSA response rate, defined as the proportion of subjects achieving a ≥ 50% reduction in PSA at any point after starting therapy. Secondary endpoints included median time to PSA progression, duration of response (DOR), and overall survival (OS). Results: Fourteen patients were screened, and thirteen patients were initiated on protocol therapy. Median age was 77 years (range 55-90). Twelve patients (92%) had bone metastases. Four patients (30%) had bone and visceral metastases. The PSA response rate was 76.9% [95% confidence interval (CI), 46.2-94.9], comprising of ten PSA responses. Two patients had a best response of stable disease, yielding a disease control rate of 92% [95% CI, 57.2-98.2]. Median time to PSA progression was 8 months [95% CI, 3.5-8.7]. Median duration of response was 7.3 months [95% CI, 4.8-13.2]. On 5-year follow-up, median overall survival was 35.1 months [95% CI, 25.7-57.7]. The most frequently reported ( > 15%) non-hematologic adverse events included diarrhea, nausea, vomiting, peripheral neuropathy, weight loss, fatigue, onycholysis, and alopecia. One patient (7%) experienced febrile neutropenia. No patients experienced grade 3 or above anemia. Conclusions: The combination of docetaxel with lycopene led to improved PSA response rate and tolerability in patients with advanced castrate resistant prostate cancer. Docetaxel plus lycopene merits further research in this patient population. Clinical trial information: NCT01882985.