| Adding paclitaxel to radiation therapy appears to benefit patients with locally advanced prostate cancer who are receiving hormone ablation Adding paclitaxel to radiation therapy appears to benefit patients with locally advanced prostate cancer who are receiving hormone ablation, according to an article in the June 18 issue of the Journal of Clinical Oncology. The combined phase I/II trial, which was conducted at the New York University Cancer Institute, was designed to determine the maximum tolerated dose (MTD) of concurrent paclitaxel and radiation therapy in this patient population. The total of 22 men with clinical stage T2-4 disease had Gleason scores greater than 7, prostate specific antigen levels greater than 10 ng/mL, or positive lymph node involvement. Median age was 59 years; median prostate specific antigen level was 22.4. When stratified by stage, there were three patients with T1 disease, eight with T2, 11 with T3; five had positive nodes. Hormonal ablation was begun three months before concurrent chemoradiation and was given for nine months. Radiation was delivered daily (1.8 Gy) with concurrent twice-weekly paclitaxel (30 mg/m2). The whole pelvis was irradiated to 39.6 Gy. The radiation dose was escalated as follows: 63 Gy, 66.6 Gy, 70.2 Gy, and 73.8 Gy. The last radiation therapy dose level was fixed at 73.8 Gy. No grade 3 toxicities occurred at 63 Gy. Grade 3 diarrhea occurred in three patients at 66.6 Gy. The protocol was amended to treat prostate volume first followed by the whole pelvis. No grade 3 toxicities were observed at 70.2 Gy. One patient experienced grade 3 diarrhea at 73.8 Gy. Five additional patients were treated to 73.8 Gy without grade 3 toxicity, which established the mean tolerated dose for combined paclitaxel and radiation as 73.8 Gy. At a median of 38 months follow-up (range, 9 to 87 months), 21 (95 percent) of 22 patients were alive; of the 22, 6 (27 percent) of 22 had developed recurrence. The key element in the study's design was adding the chemotherapy. Normally patients undergo radiation and hormonal ablation solely. Nicholas Sanfilippo, MD, said "Our study shows that concurrent paclitaxel and radiation therapy is well tolerated and early clinical results are encouraging in a patient population with high risk tumor features." Recovery of gonadal function occurred in the majority of patients, and the authors encourage testing in a phase III setting. |