Phase I Study of Bi-weekly Paclitaxel and Definitive Radiation in Androgen Ablated Locally Advanced Prostate Cancer

Article Outline

• Purpose/Objectives
• Materials/Methods
• Results
• Conclusions
• Copyright

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Purpose/Objectives 

A Phase I trial was conducted to determine the maximum tolerated dose (MTD) of the combination of concurrent paclitaxel (fixed dose of 30 mg/m² twice a week during radiotherapy) and definitive radiation therapy (RT) in patients with locally advanced prostate cancer (LAPC).

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Materials/Methods 

Eligible patients were LAPC carriers, defined as clinical stage T2/T3 with Gleason score >7 and/or PSA >10 ng/ml; and/or pathologic stage TxN1. All patients underwent hormonal ablation for a total of 9 months which was initiated at least 3 months prior to the beginning of RT. Treatment consisted of daily three-dimensional conformal RT with concurrent paclitaxel given twice weekly at a dose of 30 mg/m². Radiation was delivered at 1.8 Gy per fraction and the total dose was escalated as it follows: 63 Gy, 66.6 Gy, 70.2 Gy, and 73.8 Gy. The latter dose was pre-determined as the last dose level for MTD, since 73.8 Gy is the standard dose for hormonally ablated LABC treated with radiation alone. Radiation technique included treatment of the whole pelvis to 39.6 Gy using a four field box with a consecutive boost to the prostate and seminal vesicles using a six field conformal technique. No intensity modulated RT was used in this trial.

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Results 

Between January 2000 and October, 2006, 22 patients were enrolled in this IRB-approved combined modality protocol. Median age was 59 (range 48–72) and median PSA was 22.4 (range, 2.8–113). Clinical T-stages were: T1 (n = 3), T2 (n = 8), and T3 (n = 11) Five patients were pN1. One patient received prescribed RT but did not receive the first 2 doses of chemotherapy and is included in the analysis. All other patients received the prescribed treatment.

Initially the study was designed to treat whole pelvis followed by the boost to the prostate. The median clinical target volume for the boost was 70 cc (range, 29–99). No grade 3 toxicities occurred at the first dose level of 63 Gy with concurrent chemotherapy. Grade 1–2 toxicities occurred at each dose level and consisted of diarrhea in 7 (32%) patients and urinary frequency in 7 (32%).

Grade 3 diarrhea was observed in 3 patients at a dose of 66.6 Gy. The protocol was then amended to first treat the prostate boost volume, followed by treatment of the whole pelvis to 39.6 Gy. With this sequencing, no grade 3 toxicities were observed at the 70.2 Gy dose level. One patient experienced grade 3 diarrhea at 73.8 Gy an additional 5 patients were treated to 73.8 Gy without grade 3 toxicity, establishing the MTD for combined paclitaxel and RT at 73.8 Gy.

At a median follow up of 27 months (range, 1 to 69 months), 21 of 22 (95%) patients are alive. Six of 22 (27%) have had recurrence: one local, three distant, and two biochemical failures without clinical evidence of disease.

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Conclusions 

Concurrent bi-weekly paclitaxel (30 mg/m²) with RT is feasible and the MTD is 73.8 Gy. Early clinical results are promising for this subset of patients with a dire prognosis.