PURPOSE: To determine the maximum-tolerated dose (MTD) of concurrent paclitaxel and radiation therapy (RT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Eligible patients had T2-4 tumors with Gleason scores greater than 7 and/or PSA levels greater than 10 ng/mL and/or had tumors with pathologic stage TxN1. Hormonal ablation was initiated 3 months before RT and was given for 9 months. RT was delivered daily (1.8 Gy) with concurrent twice-weekly paclitaxel (30 mg/m(2)). 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 RT dose level was fixed at 73.8 Gy. RESULTS: Between January 2000 and October 2006, 22 patients were enrolled. The median age was 59 years (range, 48 to 72 years); the median PSA level was 22.4 ng/mL (range, 2.8 to 113 ng/mL). The number of patients per stage was as follows: three with T1, eight with T2, 11 with T3, and five with pN1 = 5. No grade 3 toxicities occurred at 63 Gy. Grade 3 diarrhea occurred in three patients at 66.6 Gy. The protocol then was amended to treat the 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 MTD for combined paclitaxel and RT at 73.8 Gy. At 38 months median follow-up (range, 9 to 87 months), 21 (95%) of 22 patients are alive. Six (27%) of 22 experienced recurrence. CONCLUSION: Concurrent biweekly paclitaxel with RT is feasible, with an MTD of 73.8 Gy. Recovery of gonadal function occurs in the majority of patients. These results encourage testing in a phase III setting.
PURPOSE: To determine the maximum-tolerated dose (MTD) of concurrent paclitaxel and radiation therapy (RT) in patients with locally advanced prostate cancer. MATERIALS AND METHODS: Eligible patients had T2-4 tumors with Gleason scores greater than 7 and/or PSA levels greater than 10 ng/mL and/or had tumors with pathologic stage TxN1. Hormonal ablation was initiated 3 months before RT and was given for 9 months. RT was delivered daily (1.8 Gy) with concurrent twice-weekly paclitaxel (30 mg/m(2)). 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 RT dose level was fixed at 73.8 Gy. RESULTS: Between January 2000 and October 2006, 22 patients were enrolled. The median age was 59 years (range, 48 to 72 years); the median PSA level was 22.4 ng/mL (range, 2.8 to 113 ng/mL). The number of patients per stage was as follows: three with T1, eight with T2, 11 with T3, and five with pN1 = 5. No grade 3 toxicities occurred at 63 Gy. Grade 3 diarrhea occurred in three patients at 66.6 Gy. The protocol then was amended to treat the 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 MTD for combined paclitaxel and RT at 73.8 Gy. At 38 months median follow-up (range, 9 to 87 months), 21 (95%) of 22 patients are alive. Six (27%) of 22 experienced recurrence. CONCLUSION: Concurrent biweekly paclitaxel with RT is feasible, with an MTD of 73.8 Gy. Recovery of gonadal function occurs in the majority of patients. These results encourage testing in a phase III setting.
Authors: Xiang Liu; Joseph C Cheng; Lorianne S Turner; Saeed Elojeimy; Thomas H Beckham; Alicja Bielawska; Thomas E Keane; Yusuf A Hannun; James S Norris Journal: Expert Opin Ther Targets Date: 2009-12 Impact factor: 6.902
Authors: Ayman E M Mahdy; Joseph C Cheng; Jun Li; Saeed Elojeimy; William D Meacham; Lorianne S Turner; Aiping Bai; Christopher R Gault; Alex S McPherson; Nicole Garcia; Thomas H Beckham; Antonio Saad; Alicja Bielawska; Jacek Bielawski; Yusuf A Hannun; Thomas E Keane; Mohhammed I Taha; Hisham M Hammouda; James S Norris; Xiang Liu Journal: Mol Ther Date: 2008-12-23 Impact factor: 11.454