Radiation Therapy Oncology Group P-0014: a phase 3 randomized study of patients with high-risk hormone-naive prostate cancer: androgen blockade with 4 cycles of immediate chemotherapy versus androgen blockade with delayed chemotherapy.
Currently, approximately 30,000 men die annually of metastatic, hormone-refractory prostate cancer. Androgen blockade is palliative and is generally effective for an average of 2 to 3 years until a patient develops androgen-independent disease. Newer chemotherapeutic regimens can induce remissions in approximately 50% of patients; however, median survival for patients with androgen-independent disease is still 8 to 12 months. The strategy of using chemotherapy regimens after androgen blockade has been proved noncurative, and new approaches are needed to attempt to cure patients with advanced disease. It has been demonstrated in the preclinical setting that androgen withdrawal induces apoptosis in cancer cells in both the Shinogi breast cancer model and the LNCaP prostate cancer model. In both of these models, androgen withdrawal was not curative, and the tumors grew back in a hormone-independent state. It is possible that the addition of chemotherapy at the time of initial androgen ablation will improve cell kill by potentiating apoptosis, thereby killing cells that might otherwise have mutated to the androgen-independent state if allowed to continue to cycle and grow. The rationale behind Radiation Therapy Oncology Group (RTOG) P-0014 is to demonstrate in a randomized phase 3 trial that giving patients chemotherapy at the beginning of androgen blockade may improve patient survival.
Pienta
Kenneth J
KJ
Department of Internal Medicine, Michigan Urology Center, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-0946, USA. kpienta@umich.edu
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001918:Brachytherapy; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D015337:Multicenter Studies as Topic / Q000379:methods*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012306:Risk; D016879:Salvage Therapy; D016019:Survival Analysis
D000726:Androgen Antagonists; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal