Adjuvant Weekly Docetaxel for Patients With High Risk Prostate Cancer After Radical Prostatectomy: A Multi-Institutional Pilot Study

Article Outline

• Abstract
• Methods
  • Patient Population
  • Treatment and Monitoring
  • Sample Size Justification
  • PFS Analysis
  • Predicted PFS Analysis
• Results
  • Patient Cohort
  • Toxicity
  • Survival Update and PFS Analysis
• Discussion
• Conclusions
• Acknowledgments
• References
• Copyright

Purpose

Patients with adverse pathological features are at high risk for recurrence following radical prostatectomy. To improve outcomes in this population we performed a phase II study of adjuvant docetaxel in these high risk patients.

Materials and Methods

Patients with nonmetastatic radical prostatectomy at greater than 50% risk for recurrence by 3 years were eligible. Pathological findings were centrally reviewed and risk assessment was based on a validated multivariate Cox proportional hazards model. Treatment consisted of 6 cycles of 35 mg/m² docetaxel weekly given 4 to 12 weeks following surgery. Progression was defined as a prostate specific antigen of 0.4 ng/ml or greater, radiological/pathological evidence of recurrent disease or death from any cause. To screen for the potential benefit of adjuvant weekly docetaxel we used nomogram predicted progression-free survival as a historical control.

Results

A total of 77 patients were registered between April 2002 and January 2004. Two patients had grade IV hyperglycemia and 20 had grade III toxicity. At a median followup of 29.2 months (range 1.6 to 39.2) 46 of 76 evaluable cases (60.5%) progressed. Observed median progression-free survival was 15.7 months (95% CI 12.8–25.1). Predicted median progression-free survival in a matched population was 10 months. Seven patients died, including 4 of prostate cancer, 1 with intra-abdominal bleeding during treatment and 2 of pneumonia and sudden cardiac death, respectively, following treatment.

Conclusions

Adjuvant docetaxel for prostate cancer is feasible with significant reversible but acceptable toxicity. The actual median progression-free survival of 15.7 months was longer than the nomogram predicted rate for this patient population. Adjuvant docetaxel treatment should be further evaluated in phase III trials in patients with high risk prostate cancer.

Key Words: prostate, prostatic neoplasms, drug therapy, prostatectomy, mortality

Abbreviations and Acronyms: CT, computerized tomography, PFS, progression-free survival, PSA, prostate specific antigen, RP, radical prostatectomy, Rw′, weighted risk of recurrence, SWOG, Southwest Oncology Group

Prostate cancer remains the most common malignant neoplasm diagnosed in adult males in the United States. Approximately 85% of all cases diagnosed yearly are clinically localized and most are treated with RP or radiation therapy.¹ Unfortunately 30% to 40% of these men show evidence of increasing serum PSA within 10 years of treatment.² Pathological risk factors for disease recurrence and disease specific survival following RP include positive surgical margins, extracapsular disease, high Gleason score, positive lymph nodes and positive seminal vesicles.² The natural history of patients with unfavorable risk factors suggests micrometastatic disease at diagnosis.

There is no current adjuvant standard of care for patients with high risk disease following RP. Adjuvant hormone therapy improves survival in patients with positive lymph nodes,³ although it is unknown if this survival advantage translates to other high risk populations. Clinical trials with neoadjuvant hormone ablation showed a disease specific and overall survival benefit when combined with external beam radiation therapy⁴ but not for surgery.⁵ Postoperative radiation therapy is an important approach for patients with clinical and pathological findings that are consistent with a high risk of local relapse. Retrospective studies demonstrated that adjuvant radiation therapy improves PFS.⁶, ⁷ However, 2 recent prospective trials demonstrated improved biochemical and local relapse-free survival but no decrease in distant relapse rates, disease specific or overall survival.⁸, ⁹

These data strongly support the hypothesis that many patients with locally advanced prostate carcinoma have occult distant metastases at presentation and, therefore, they are unlikely to be cured by local therapy alone. Therefore, adjuvant systemic approaches should be evaluated in an attempt to decrease recurrence rates and improve survival. Randomized clinical trials demonstrated that docetaxel based chemotherapy improves survival in hormone refractory prostate carcinoma cases.¹⁰, ¹¹ Studies of colon, breast and lung carcinoma showed that regimens with comparable levels of therapeutic efficacy in the metastatic setting are associated with disease specific and survival improvements in the adjuvant setting in patients at high risk.¹², ¹³, ¹⁴

We report PFS and toxicity in a post-RP adjuvant pilot study in patients at high risk for occult metastatic disease following RP. To screen for the potential benefit of adjuvant weekly docetaxel we used nomogram predicted PFS as a historical control.

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Methods 

Patient Population 

Patients were identified prospectively at participating institutions. All underwent RP for presumed localized prostate carcinoma. Pathological findings were centrally reviewed and the risk of recurrence was calculated using a validated model based on a multivariate Cox proportional hazards model of Rw′.¹⁵ Patients were required to have an Rw′ of 2.84 or greater, which translated to a risk of biochemical recurrence of 50% or more at 3 years. To be eligible patients were not required to have undetectable serum PSA after RP. Additional inclusion criteria were RP within 1 to 3 months of study drug initiation, no radiographic evidence of distant metastasis, no organ dysfunction, Eastern Cooperative Oncology Group performance status 0 or 1, no other malignancy for 5 years or more except nonmelanomatous skin cancer, no contraindication for taxane administration and no prior radiotherapy or systemic treatment for prostate cancer. All participants provided signed, institutional review board approved informed consent.

Treatment and Monitoring 

Treatment consisted of 6 cycles of 35 mg/m² docetaxel intravenously on days 1, 8 and 15 of each 28-day cycle. Before each docetaxel infusion all patients were premedicated with 10 mg dexamethasone. Pretreatment evaluation consisted of physical examination, routine chemical profile, complete blood count, PSA, computerized tomography and bone scan. Patients were reevaluated weekly during treatment and then every 3 months following treatment with physical examination, routine chemical profile, complete blood count and PSA measurement. The first PSA evaluation was done after completion of the 6-month treatment period. Bone scan and computerized tomography were done at progression. Adverse events were evaluated by National Cancer Institute Common Toxicity Criteria.

Patients were allowed to have dose reductions of docetaxel to 28 mg/m² and then 22 mg/m² for grade 3 or 4 neutropenia, thrombocytopenia, liver function abnormalities, neurotoxicity or stomatitis. After the completion of treatment patients were followed with serum PSA measurement every 3 months until progression.

Sample Size Justification 

Accrual of 75 patients was deemed sufficient to detect an absolute 20% difference in the 2-year PFS rate between the experimental treatment and historical control groups with a nominal 2-sided 0.05 significance level and 90% power within the range of 30% to 60% PFS rate of historical controls.

PFS Analysis 

PFS was defined as the time from surgery to progression. Progression was defined as 1) PSA 0.4 mg/ml or greater, as confirmed by a repeat test 2 to 4 weeks later, 2) radiological or clinical evidence of metastatic disease, as confirmed by histology in the absence of increased PSA, or 3) death from any cause in the absence of disease progression. In patients who did not have disease progression and were still on study at the time of analysis, who were given new antitumor treatment or who were removed from study followup before documentation of progressive disease PFS was censored at the last date that the patient was known to be disease-free.

The PFS distribution was estimated and analyzed using the Kaplan-Meier method. Median PFS was described with the 95% CI using the Brookmeyer and Crowley method. The probability of being progression-free at 12 and 24 months was derived from this analysis.

As an exploratory analysis, a Cox proportional hazards regression model was developed to explore the multivariate association between the PFS rate and 5 prognostic factors, including lymph node involvement (positive vs negative), pathological Gleason sum, preoperative PSA, seminal vesicle involvement (positive vs negative) and surgical margins (positive vs negative). The HR with the 95% CI was calculated.

Predicted PFS Analysis 

Predicted PFS probabilities in each patient were calculated using the corrected group prognosis method. This approach uses the Cox regression model underlying a modified version of a published nomogram¹⁶ to predict progression in each patient. Using the corrected group prognosis method the probabilities at each progression time were then averaged across patients.

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Results 

Patient Cohort 

A total of 77 patients were enrolled from April 2002 to January 2004. Median followup as of October 2005 was 29.2 months (range 1.6 to 39.2). Table 1 lists patient characteristics. While preoperatively 74% of patients had T1 or T2 disease, final pathological evaluation revealed that only 1.3% had pT2Nx disease. Pathological findings showed positive seminal vesicles in 50 of 77 cases (65%), positive lymph nodes in 29 of 77 (38%) and positive margins in 50 of 77 (65%). Pathological Gleason Score was 7, 8, 9 and 10 in 44%, 14%, 38% and 4% of patients, respectively. Reflecting the advanced nature of the disease, average Rw′ was 4.07 (range 2.85 to 5.93).

Table 1. Baseline patient and tumor characteristics

Demographics
No. pts	77
Mean age (range)	60 (43–76)
Mean ng/ml PSA at diagnosis (range)	15.1 (0.62–83.1)
Rw′ (range)	4.07 (2.85–5.93)
No. ethnicity (%):
White	72 (93.5)
Black	3 (3.9)
Other	2 (2.6)
No. clinical stage (%):
cT1a	1 (1.3)
cT1c	24 (31.2)
cT2	32 (41.6)
cT3	9 (11.7)
cTxN1	2 (2.6)
Unknown	11 (18.1)
No. pathological stage (%):
pT2a	0
pT2bN0	1 (1.3)
pT3aN0	16 (20.1)
pT3bN0	31 (40.3)
pTxN+	29 (37.7)
No. pos seminal vesicles (%)	50 (64.9)
No. pos surgical margins (%)	50 (64.9)
No. pathological Gleason sum(%):
2–6	0
3+4 = 7	8 (10.4)
4+3 = 7	26 (33.8)
8	11 (14.3)
9	29 (37.7)
10	3 (3.9)

Toxicity 

Table 2 lists toxicity data. Grade I/II toxicity in the absence of grade III/IV toxicity occurred in 54 patients (70%). Grade III toxicity occurred in 20 patients (26%), including dyspnea in 4, fatigue and cardiac arrhythmia in 3, and diarrhea, dizziness, nausea, acute vascular leak syndrome and hyperglycemia in 2. Grade IV toxicity occurred in 3 patients (4%), including hyperglycemia that was most likely related to dexamethasone in 2, which resolved, and gastrointestinal bleeding resulting in death in 1, which was possibly related to treatment. One patient with pulmonary fibrosis died 717 days following treatment, which was possibly related to docetaxel.

Table 2. Toxicity data

No. Pts (%)	National Ca Institute Definition
Grade I–II:⁎
69(89.6)	Fatigue
63(81.8)	Taste change
59(76.6)	Nail changes
53(68.8)	Alopecia
44(57.1)	Sensory neuropathy
41(53.2)	Infection without neutropenia
40(51.9)	Allergic rhinitis, diarrhea, tearing
37(48.1)	Nausea, edema
35(45.5)	Insomnia
34(44.2)	Dyspepsia, flushing
32(41.6)	Epistaxis
30(39.0)	Dyspnea
29(37.7)	Cough
28(36.4)	Pain, rash
25(32.5)	Anorexia
Grade III:
4(5.2)	Dyspnea
3(3.9)	Fatigue, supraventricular arrhythmia
2(2.6)	Acute vascular leak syndrome, diarrhea, dizziness, hyperglycemia, nausea
1(1.3)	Hypersensitivity, arrhythmia, constipation, dehydration, erectile dysfunction, infection/febrile neutropenia, insomnia, leukocytes, neuropathy, pleural effusion, pneumonitis, pulmonary fibrosis, rash, increased serum glutamic-pyruvic transaminase, sinus tachycardia, stomatitis
Grade IV:
2(2.6)	Hyperglycemia
1(1.3)	Gastrointestinal

Treatment was discontinued early in 10 patients due to toxicity in 3, distant metastases in 2 and death in 1. In an additional 4 patients treatment was discontinued with no evidence of dose limiting toxicity. Excluding the 2 patients with progression while on treatment and the 1 who withdrew from treatment after 1 dose, all patients received at least 4 cycles. Delays were required in 4 patients due to toxicity and in 4 due to errors in pretreatment dexamethasone dosing. Dose reductions were required in 4 patients.

Survival Update and PFS Analysis 

A total of 76 patients were evaluable for efficacy analysis. One patient withdrew from study after a single dose and was lost to followup. Seven of 76 patients (9.2%) had died by December 20, 2005. The primary cause of death was disease progression in 4 patients, study medication toxicity in 1 and other causes in 2. At a median followup of 29.2 months 46 cases (60.5%) had progressed. One and 2-year PFS was 63.2% (95% CI 52.3%–74.0%) and 41.7% (95% CI 30.5%–52.8%), respectively. Median PFS was 15.7 months (95% CI 12.8–25.1). Predicted PFS using the validated nomogram was 10 months (fig. 1).

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• Fig. 1. 

  Kaplan-Meier and Kattan nomogram PFS in 76 patients

Of 67 patients with PSA values postoperatively and before docetaxel administration 27 had detectable and 40 had undetectable PSA (0.4 or greater and less than 0.4 ng/ml, respectively). Of the 40 patients with undetectable PSA 24 had no progression at the time of analysis, 12 had biochemical failure (PSA 0.4 ng/ml or greater) and 1 had metastatic disease. In addition, 2 patients died before documented disease progression and 1 received additional treatment before failure. One and 2-year PFS in this cohort was 87.5% (95% CI 77.3%–97.7%) and 67.2% (95% CI 52.5%–81.8%), respectively. Median PFS was not attained (fig. 2). Only 1 of the 27 patients with detectable PSA before treatment did not show progression. The Cox proportional hazards regression model revealed that lymph node involvement and pathological Gleason sum were associated with treatment failure (HR 2.49, 95% CI 1.22–5.08, p = 0.0123 and HR 1.46, CI 1.04–2.03, p = 0.0269, respectively, table 3).

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• Fig. 2. 

  Kaplan-Meier and Kattan nomogram predicted PFS in 40 patients with undetectable PSA at baseline.

Table 3. Cox proportional hazard regression model parameter estimates of PFS as function of tumor features

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Discussion 

Up to 40% of men who undergo RP have evidence of disease progression and this rate is substantially worse in patients with high stage disease.² Optimal treatment in men at high risk for relapse following definitive therapy remains poorly defined. Treatment options that have been advocated include adjuvant hormone therapy³, ¹⁷ or adjuvant external beam radiotherapy.⁶, ⁷, ⁸, ⁹ In this pilot trial men with high risk prostate cancer received docetaxel weekly.

The patient population entered in this study had clinical and pathological parameters indicative of an extremely high risk of relapse and death due to disease. Of the patients 98.7% had nonorgan confined disease, 55.8% had Gleason sum 8–10, 64.9% had positive margins, 64.9% had positive seminal vesicles and 37.6% had nodal involvement. This is reflected in the predicted PFS of only 10 months in the cohort as a whole.¹⁶ While data are preliminary and limited by the historical nature of this comparison, the 63.2% 1-year PFS and the median PFS of 15.7 months appear to be better than the predicted PFS.

In this study toxicity was moderate and mostly reversible. One patient had progressive pulmonary insufficiency due to interstitial pulmonary disease, which was most likely related to docetaxel treatment. The patient had preexisting pulmonary disease, which probably contributed significantly to his death 2 years following treatment. Three patients had grade 4 toxicity, including 2 with steroid induced hyperglycemia that resolved with treatment, and 1 with fatal gastrointestinal bleeding during treatment, which was also most likely related to dexamethasone. Since this was a nonrandomized trial, it is not possible to know whether toxicity was due to underlying patient characteristics or to treatment. While prior studies of adjuvant docetaxel for other malignancies did not demonstrate significant toxicity, because of the possibility that toxicity is high in this population, we do not recommend adjuvant docetaxel outside of the confines of a clinical trial.

The most common adjuvant treatment option following RP is radiotherapy, which appears to affect predominantly locoregional disease. Retrospective studies consistently demonstrate that adjuvant radiation therapy improves PFS⁶, ⁷ but not overall or prostate cancer specific survival.⁷ The European Organization for Research and Treatment of Cancer, and SWOG recently reported 2 randomized, phase III studies of adjuvant radiotherapy following RP.⁸, ⁹ Each trial demonstrated a statistically significant improvement in biochemical-free and relapse-free survival. However, each trial failed to show an impact on distant metastases or overall survival, although these end points approached statistical significance in the SWOG trial.⁹

Importantly the patient populations studied in these adjuvant radiotherapy trials were dramatically different than those in this series. In the SWOG study 0% of patients had positive lymph nodes, 57% had Gleason sum 6 or less and 10% had positive seminal vesicles.⁹ In contrast, in this study 38% of patients had positive lymph nodes, 0% had Gleason sum 6 or less and 68% had positive seminal vesicles.

The adjuvant radiotherapy data are most consistent with effectively decreasing the incidence of local recurrences but not affecting systemic disease. Additional followup is needed to allow more definitive conclusions regarding the effects of adjuvant radiation therapy on the development of distant metastasis. Nonetheless, results at this time support the need to vigorously explore the role of adjuvant systemic approaches to achieve more adequate disease control.

The only adjuvant systemic approach previously available is hormone ablation. Messing et al randomized 98 men with positive lymph nodes at RP to immediate hormone ablation vs ablation at the time of metastasis and noted a survival advantage for early androgen ablation.³ No other prospective study to date has demonstrated a survival advantage in patients undergoing adjuvant hormone ablation.¹⁷

Several groups explored neoadjuvant docetaxel.¹⁸, ¹⁹ Each trial enrolled patients with increased PSA, Gleason score 8 or greater and clinical stage T2b or greater. The primary end point was a pathological complete response. However, no trial achieved this goal. Recurrence rates were relatively high at greater than 30% at less than 2 years.¹⁸, ¹⁹ This should not be seen as an indication of a lack of efficacy. These data simply suggest that these patients have aggressive disease.

Our study provides evidence that adjuvant docetaxel is feasible. Future studies should build on this pilot. 1) Our selection of weekly docetaxel for this adjuvant study was based on the efficacy and favorable side effect profile, as known at the time of study design.²⁰ Subsequently published phase III data demonstrated that only the schedule of docetaxel 3 times weekly and not weekly is associated with a survival advantage.¹⁰ Therefore, future studies with adjuvant docetaxel should include the 3-week schedule. 2) We included 27 patients with biochemically detectable disease following surgery. These patients did not receive classic adjuvant treatment, but rather therapy for persistent disease. Reflecting the more advanced nature of their disease, these patients did particularly poorly. Future studies should focus on delivering true adjuvant therapy or treatment for persistent disease.

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Conclusions 

This phase II trial of adjuvant docetaxel following RP demonstrates that adjuvant treatment has significant but acceptable toxicity in a high risk population. The observed median PFS of 15.7 months is longer than the predicted 10 months, suggesting a potential for this systemic treatment to modify the outcome in patients at high risk. The results of docetaxel for hormone refractory prostate carcinoma and this pilot study provide the impetus for a phase III trial testing the role of adjuvant androgen deprivation with or without docetaxel in patients with high risk localized disease and undetectable PSA after RP.

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Acknowledgments 

Jane Diamond, Johanna Wolski, Arkady Shpilsky and Li Li provided assistance.

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References 

1. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10
   • View In Article
   • MEDLINE
   • CrossRef
2. Roehl KA, Han M, Ramos CG, Antenor JA, Catalona WJ. Cancer progression and survival rates following anatomical radical retropubic prostatectomy in 3,478 consecutive patients: long-term results. J Urol. 2004;172:910
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (95 KB)
   • CrossRef
3. Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med. 1999;341:1781
   • View In Article
   • MEDLINE
   • CrossRef
4. Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, et al. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002;360:103
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (104 KB)
   • CrossRef
5. Klotz LH, Goldenberg SL, Jewett MA, Fradet Y, Nam R, Barkin J, et al. Long-term followup of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy. J Urol. 2003;170:791
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (80 KB)
   • CrossRef
6. Catalona WJ, Smith DS. Cancer recurrence and survival rates after anatomic radical retropubic prostatectomy for prostate cancer: intermediate-term results. J Urol. 1998;160:2428
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (692 KB)
   • CrossRef
7. Nilsson S, Norlen BJ, Widmark A. A systematic overview of radiation therapy effects in prostate cancer. Acta Oncol. 2004;43:316
   • View In Article
   • MEDLINE
   • CrossRef
8. Bolla M, van Poppel H, Collette L, van Cangh P, Vekemans K, Da Pozzo L, et al. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911). Lancet. 2005;366:572
   • View In Article
   • Abstract
   • Full Text
   • Full-Text PDF (111 KB)
   • CrossRef
9. Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA. 2006;296:2329
   • View In Article
   • CrossRef
10. Tannock IF, deWit R, Berry WR, Horti J, Pluzanska A, Chi KN, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502
    • View In Article
    • CrossRef
11. Petrylak DP, Tangen CM, Hussain MH, Lara PN, Jones JA, Taplin ME, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513
    • View In Article
    • CrossRef
12. Arriagada R, Bergman B, Dunant A, LeChevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004;350:351
    • View In Article
    • CrossRef
13. Andre T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004;350:2343
    • View In Article
    • CrossRef
14. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (423 KB)
    • CrossRef
15. Roberts WW, Bergstralh EJ, Blute ML, Slezak JM, Carducci M, Han M, et al. Contemporary identification of patients at high risk of early prostate cancer recurrence after radical retropubic prostatectomy. Urology. 2001;57:1033
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (174 KB)
    • CrossRef
16. Kattan MW, Wheeler TM, Scardino PT. Postoperative nomogram for disease recurrence after radical prostatectomy for prostate cancer. J Clin Oncol. 1999;17:1499
    • View In Article
    • MEDLINE
17. Wirth MP, See WA, McLeod DG, Iversen P, Morris T, Carroll K. Bicalutamide 150 mg in addition to standard care in patients with localized or locally advanced prostate cancer: results from the second analysis of the early prostate cancer program at median followup of 5.4 years. J Urol. 2004;172:1865
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (219 KB)
    • CrossRef
18. Dreicer R, Magi-Galluzzi C, Zhou M, Rothaermel J, Reuther A, Ulchaker J, et al. Phase II trial of neoadjuvant docetaxel before radical prostatectomy for locally advanced prostate cancer. Urology. 2004;63:1138
    • View In Article
    • Abstract
    • Full Text
    • Full-Text PDF (109 KB)
    • CrossRef
19. Febbo PG, Richie JP, George DJ, Loda M, Manola J, Shankar S, et al. Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer. Clin Cancer Res. 2005;11:5233
    • View In Article
    • MEDLINE
    • CrossRef
20. Beer TM, Pierce WC, Lowe BA, Henner WD. Phase II study of weekly docetaxel in symptomatic androgen-independent prostate cancer. Ann Oncol. 2001;12:1273
    • View In Article
    • MEDLINE
    • CrossRef