Source: Gastroenterology  |  Posted 9 years ago

By Peggy Peck

ORLANDO, FL -- May 21, 2002 -- Results of a dose-escalating study of weekly paclitaxel and concurrent radiation and androgen ablation in men with recurrent or locally advanced prostate cancer suggest that this new approach is both feasible and well tolerated.

Arif Hussain, MD, and colleagues from the University of Maryland Greenebaum Cancer Center, Baltimore, Maryland presented the findings on May 20 at the 38th Annual Meeting of the American Society for Clinical Oncology (ASCO).

Dr. Hussain noted that previous studies demonstrated that a combination of androgen ablation and radiation is more effective than radiation alone in men with locally advanced prostate cancer. Recently, clinicians are attempting this same approach in men with recurrent or residual prostate cancer post-prostatectomy. Paclitaxel is known for its radiosensitizing and cytotoxic properties and has been used with radiation to treat other malignancies, but has not been adequately investigated in prostate cancer, said Dr. Hussain.

Dr. Hussain and colleagues reported on an ongoing study evaluating escalating doses of paclitaxel with concurrent radiation and androgen ablation in two groups of patients: those with residual disease or rising prostate specific antigen (PSA) after surgery (group 1) and patients with locally advanced prostate cancers (group 2).

He said luteinizing hormone-releasing hormone (LHRH) agonist was given first and three days later weekly paclitaxel (for seven consecutive weeks) was initiated. Radiation was started 24 hours after the first paclitaxel dose. Androgen ablation was then given for four months to two years depending upon risk features.

Paclitaxel was dose-escalated from 40 mg/m?/week to 50 mg/m?/week and finally to 60 mg/m?/week. Patients in group 1 received 64.8 Gy and patients in group 2 received 70.2 Gy of total radiation dose to the prostate bed.

Dr. Hussain enrolled 15 patients in group 1 and 16 in group 2. In group 1 the median age was 65, Gleason score 7, and PSA 1.82. In group 2 the median age was 68.5, Gleason score 9, and PSA 29.9.

Acute toxicities in group 1 at the 40 mg dose were diarrhea and urinary retention. At the 50 mg dose, toxicities included diarrhea and dysuria. In group 2, toxicities include hematuria, rectal bleeding, urinary retention, diarrhea, and rectal pain.

Of the 105 total weekly doses of paclitaxel delivered in group 1, three doses were held for grade 2-3 toxicities. Of the 112 total weekly doses of paclitaxel delivered in group 2, seven doses were held. Paclitaxel dose was reduced in four patients and radiation was delayed in two patients due to toxicity.