Long-Term Follow-Up of a Prospective Trial of Trimodality Therapy of Weekly Paclitaxel, Radiation, and Androgen Deprivation in High-Risk Prostate Cancer With or Without Prior Prostatectomy

• Published in: International journal of radiation oncology, biology, physics Vol. 82; no. 1; pp. 167 - 174
• Main Authors: Hussain, Arif, M.D, Wu, Yin, M.D, Mirmiran, Alireza, M.D, DiBiase, Steven, M.D, Goloubeva, Olga, Ph.D, Bridges, Benjamin, M.D, Mannuel, Heather, M.D, Engstrom, Christine, Ph.D, Dawson, Nancy, M.D, Amin, Pradip, M.D, Kwok, Young, M.D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 2012; Elsevier
• Subjects: Age; Aged; Aged, 80 and over; Androgen Antagonists - therapeutic use; ANDROGENS; ANTIGENS; Antineoplastic Agents, Phytogenic - administration & dosage; Biological and medical sciences; Chemoradiotherapy - adverse effects; Chemoradiotherapy - methods; CHEMOTHERAPY; Concurrent chemoradiation; DIARRHEA; Diarrhea - etiology; Drug Administration Schedule; Gynecology. Andrology. Obstetrics; HAZARDS; Hematology, Oncology and Palliative Medicine; High-risk prostate cancer; Humans; LEUKOPENIA; Leukopenia - etiology; Male; Male genital diseases; Medical sciences; Middle Aged; Multimodality therapy; Neoplasm Grading; NEOPLASMS; Nephrology. Urinary tract diseases; Paclitaxel - administration & dosage; PATIENTS; Post-prostatectomy radiation; Prospective Studies; PROSTATE; Prostate-Specific Antigen - blood; Prostatectomy; Prostatic Neoplasms - blood; Prostatic Neoplasms - mortality; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; RADIATION DOSES; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy Dosage; Survival Analysis; TOXICITY; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urination Disorders - etiology; Multimodality therapy; Post-prostatectomy radiation; High-risk prostate cancer; Concurrent chemoradiation; Antineoplastic agent; High risk; Prostate disease; Concurrent; Administration schedule; Chemoradiotherapy; Prospective; Cancerology; Androgen deprivation; Surgery; Taxane derivatives; Paclitaxel; Clinical trial; Antimitotic; Male genital diseases; Urinary system disease; Androgen deprivation therapy; Malignant tumor; Radiotherapy; Long term; Chemotherapy; Treatment; Follow up study; Prostatectomy; Combined treatment; Prostate cancer; Cancer
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2010.09.009

Purpose Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). Methods and Materials Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) ≥0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8–10; 3) GS 7 + PSA 10–20 ng/mL; or 4) PSA 20–150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m2 /wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). Results Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45–86 years), PSA 5.9 (0.1–92.1 ng/mL), GS 8 (6–9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8–82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. Conclusions In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m2 /week in RP patients and 60 mg/m2 /week in LAPC patients is feasible and well-tolerated.