Elsevier

Urology

Volume 63, Issue 6, June 2004, Pages 1138-1142
Urology

Adult urology
Phase II trial of neoadjuvant docetaxel before radical prostatectomy for locally advanced prostate cancer

https://doi.org/10.1016/j.urology.2004.01.040Get rights and content

Abstract

Objectives

To perform a Phase II trial of docetaxel administered on a weekly schedule for 6 weeks before radical prostatectomy (RP) in patients with locally advanced prostate cancer.

Methods

Treatment consisted of six doses of docetaxel 40 mg/m2 intravenously administered weekly for 6 weeks followed by RP. Eligibility criteria included clinical Stage T2b, prostate-specific antigen (PSA) level 15 ng/mL or greater or Gleason sum 8 or greater, and no evidence of metastatic disease. The primary endpoint was feasibility and drug-related and surgical-related toxicities. Secondary endpoints included pre-RP PSA level, local response, pathologic outcomes, and time to PSA failure.

Results

Twenty-nine patients were entered; 80% completed all 6 weeks of therapy and 97% underwent RP. The median PSA level was 12 ng/mL (range 2.5 to 43.3), the median Gleason sum was 8 (range 6 to 9), and all had Stage T2b or greater disease. A statistically significant reduction in the prechemotherapy versus postchemotherapy mean PSA level was observed (12.00 ± 1.86 ng/mL versus 8.42 ± 1.63 ng/mL, P <0.03), with 79% of patients experiencing some reduction and 24% a more than 50% reduction in PSA level in response to docetaxel alone. No unexpected toxicities and no intraoperative complications occurred. Pathologic analysis demonstrated residual carcinoma in all cases. Three patients (11%) had organ-confined disease, and 26 (93%) had achieved an undetectable PSA postoperatively. At a median follow-up of 23 months (range 1.5 to 36), 20 patients were disease free with no additional therapy.

Conclusions

This trial establishes the baseline effect of short-course high-dose docetaxel alone on locally advanced prostate cancer. Additional study of this paradigm with other agents alone and in combination with docetaxel seems warranted.

Section snippets

Material and methods

Twenty-nine patients were enrolled in the study between May 2001 and April 2003. The eligibility criteria included histologically documented locally advanced prostate cancer defined by a serum PSA level of greater than 15 ng/mL (any grade or stage), clinical Stage T2b, T2c, or T3 (any PSA level or grade), or biopsy Gleason sum of 8 or greater (any stage or PSA level). Clinical stage was assigned on the basis of the digital rectal examination findings, according to the 1992 American Joint

Results

The pretreatment characteristics of the study population are outlined in Table I. The pretreatment serum PSA level ranged from 2.5 to 43.3 ng/mL (mean 12.0 ± 1.86, 95% confidence interval 8.20 to 15.8), Gleason sum from 6 to 9 (median 8), and clinical stage from T2b to T3c. The predicted likelihood of organ-confined disease for the 29 enrolled patients ranged from 3% to 34% (median 13%), as determined by the most recent Kattan nomogram.20

Treatment was generally well tolerated, with 22 patients

Comment

The need for innovative, multimodal approaches to locally advanced prostate cancer is illustrated by the results among large contemporary RP series.1, 2, 3 Although patients with favorable preoperative parameters, organ-confined disease, and negative surgical margins can expect an 8-year biochemical disease-free survival rate of 96%,3 patients with locally advanced disease fare much worse. For example, patients with a Gleason sum of 8 or greater have an actuarial 7 to 10-year biochemical

Conclusions

The results of this trial confirmed the feasibility of RP with acceptable surgical morbidity after neoadjuvant therapy with docetaxel in patients with locally advanced prostate cancer. The ultimate utility of this approach remains undefined; however, additional study of this paradigm with docetaxel in combination with agents that may augment its activity such as calcitriol and velcade or other novel single agents seems warranted.25, 26

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  • Cited by (0)

    This study was supported in part by a grant from Aventis Pharmaceuticals.

    R. Dreicer is a study investigator funded by Aventis, Millenium, Berlex, and Celgene and is a member of the speaker's bureau for Aventis. E. A. Klein is a paid consultant to Aventis.

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