Multimodal Therapy Benefits Men With Prostate Cancer Experiencing Biochemical Recurrence After Local Therapy
In men who experience biochemical disease recurrence after local therapy for prostate cancer, docetaxel, bevacizumab (Avastin), and androgen-deprivation therapy may be beneficial, according to a study by McKay et al in Cancer. Further evaluation of this combination treatment is warranted to establish the optimal dose and to minimize toxicities.
Up to 80% of men who receive local therapy for prostate cancer may experience biochemical disease recurrence, which is characterized by rising prostate-specific antigen (PSA) levels without evidence of metastatic disease. Due to the lack of established clinical trials, the standard treatment for patients with biochemical disease recurrence has not been established. The most commonly used treatment approach is androgen-deprivation therapy, but no clear consensus exists for the optimal timing of treatment.
Recent studies have demonstrated the benefit of docetaxel and androgen-deprivation therapy in men with castration-sensitive metastatic prostate cancer. The role of chemotherapy and antiangiogenic approaches within the context of prostatectomy and radiotherapy continues to be explored in randomized clinical trials.
Thus, McKay and colleagues investigated the efficacy and toxicity of docetaxel, bevacizumab, and androgen-deprivation therapy in men who experienced biochemical disease recurrence after local therapy for prostate cancer.
Study Details
Included in the phase II study were 41 men with biochemical disease recurrence who had no current evidence of prostate cancer. Of them, 36 patients underwent radical prostatectomy, 29 of whom received salvage radiotherapy and 5 of whom received radiotherapy as definitive local therapy. Patients were not eligible if they had a second malignancy within 5 years or had received active treatment with corticosteroids.
Patients received docetaxel at a dose of 75 mg/m2 intravenously every 3 weeks for four cycles, bevacizumab at a dose of 15 mg/kg intravenously every 3 weeks for eight cycles, and a luteinizing hormone-releasing hormone agonist for 18 months. Bicalutamide at a dose of 50 mg/d orally was initiated after the completion of docetaxel (at 3 months) and continued for a total of 15 months.
The primary endpoint was the percentage of patients free from PSA progression 1 year after the completion of androgen-deprivation therapy. Radiographic evidence of disease progression was considered progression regardless of PSA levels. Secondary endpoints included time to PSA progression and PSA response at the completion of docetaxel therapy and androgen-deprivation therapy.
Key Data
After the completion of androgen-deprivation therapy, the estimated probability of patients remaining free of PSA progression was 98% (95% confidence interval [CI] = 93%–100%). Of the 41 total patients, 2 developed PSA progression. Both patients had testosterone levels < 100 ng/dL. Overall, 33 patients (80%) developed PSA progression, with a median time to progression of 27.5 months (95% CI = 26–38 months). Seven patients (17%) developed metastatic prostate cancer at a median of 44.6 months.
As for associated adverse events, 16 patients (39%) experienced grade 3, and 5 patients (12%) experienced grade 4 treatment-related adverse events. Eleven patients experienced grade 3 or 4 toxicities related to bevacizumab, and 14 patients experienced grade 3 or 4 toxicities related to docetaxel. The most common grade 3 treatment-related toxicities were neutropenia (11 patients), febrile neutropenia (5 patients), and hypertension (4 patients).
Closing Thoughts
The results of this study demonstrated that the administration of docetaxel, bevacizumab, and androgen-deprivation therapy is feasible in men with biochemical disease recurrence after definitive local therapy for prostate cancer. At a median follow-up of 27.5 months, 20% of men were free of PSA disease.
The investigators concluded, “We believe that intensive multimodal systemic treatment of a limited duration may benefit a subset of patients with high-risk biochemical disease recurrence.”
Mary-Ellen Taplin, MD, of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, is the corresponding author of this article in Cancer.
This study was supported by a grant from Genentech. For full disclosures of the study authors, visit www.onlinelibrary.wiley.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
