SUMMARY: Prostate cancer is the most common cancer in American men excluding skin cancer and 1 in 7 men will be diagnosed with prostate cancer during their lifetime. It is estimated that in the United States, about 220,800 new cases of prostate cancer will be diagnosed in 2015 and over 27,000 men will die of the disease. The development and progression of prostate cancer is driven by androgens. Androgen Deprivation Therapy (ADT) has therefore been the cornerstone of treatment of advanced prostate cancer and is the first treatment intervention for hormone sensitive prostate cancer. Chemotherapy is usually considered for patients who progress on hormone therapy and TAXOTERE® (Docetaxel) has been shown to improve Overall Survival (OS) of metastatic prostate cancer patients, who had progressed on Androgen Deprivation Therapy. Two previously published trials, STAMPEDE and CHAARTED have shown that TAXOTERE® in combination with Androgen Deprivaton Therapy significantly improved Overall Survival among men with newly diagnosed hormone naïve metastatic prostate cancer. Based on this information the authors hypothesized that if chemotherapy is beneficial in metastatic hormone sensitive prostate cancer, non-metastatic, hormone-sensitive, prostate cancer, should have improved outcomes with chemotherapy, as well.
RTOG 0521 is a randomized phase III trial which enrolled 612 high-risk with localized prostate cancer and 563 patients were eligible for evaluation. High risk prostate cancer was defined as 1) Patients with Gleason score of 7-8, any T-stage and PSA of 20 ng/ml or more or 2) Gleason score of 8, T2 or more and any PSA or 3) Gleason score of 9-10, any T stage and any PSA. All patients had a PSA of 150 ng/ml or less. This study was designed to detect a 51% relative reduction in the risk of death. Patients were randomized to receive Androgen Deprivation Therapy (ADT) with LHRH agonists and Radiation Therapy to a dose of 75.6 Gy (N=281) or ADT along with Radiation Therapy and TAXOTERE® (Docetaxel) 75 mg/m2 given on Day 1, every 3 weeks, for a total of 6 cycles, along with Prednisone, starting 4 weeks after the completion of Radiotherapy (N=282). Androgen Deprivation Therapy was given for 24 months and Radiation Therapy was delivered over an 8 week period. The median age was 66 years. The median PSA level was 15.1 ng/mL, 53% had Gleason scores between 9 and 10, 27% had prostate cancer with clinical T3-4 disease and 33% had node-negative disease. The primary endpoint was Overall Survival.
With a median follow up of 5.5 yrs, the 4 year Overall Survival rates were 89% for those who received ADT and Radiation Therapy (RT) compared to 93% for men treated with ADT, RT, and TAXOTERE® chemotherapy (HR=0.68; P=0.03). The 5 year Disease Free Survival rates were 66% in the ADT plus RT versus 73% in the TAXOTERE® group (HR = 0.76; P=0.05) and there was associated reduction in the incidence of distant metastasis. There were more grade 3 and 4 hematologic toxicities in the chemotherapy arm as was expected and these toxicities were manageable.
The authors concluded that this is the first phase III study to show Overall Survival benefit when TAXOTERE® is given as adjuvant chemotherapy in high risk, hormone sensitive, prostate cancer patients with localized disease. Longer follow up will determine if the role of adjuvant chemotherapy with TAXOTERE®, in this patient population will become more established.
A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521). Sandler HM, Hu C, Rosenthal SA, et al. J Clin Oncol 33, 2015 (suppl; abstr LBA5002)