scholarly journals Phase III Trial of Androgen Ablation With or Without Three Cycles of Systemic Chemotherapy for Advanced Prostate Cancer

2008 ◽  
Vol 26 (36) ◽  
pp. 5936-5942 ◽  
Author(s):  
Randall E. Millikan ◽  
Sijin Wen ◽  
Lance C. Pagliaro ◽  
Melissa A. Brown ◽  
Brenda Moomey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Standard Therapy ◽  
Metastatic Prostate Cancer ◽  
Specific Antigen ◽  
Hormone Treatment ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Androgen Ablation ◽  
Castrate Resistant

Purpose We conducted a phase III trial in patients with previously untreated metastatic prostate cancer to test the hypothesis that three 8-week cycles of ketoconazole and doxorubicin alternating with vinblastine and estramustine, given in addition to standard androgen deprivation, would delay the appearance of castrate-resistant disease. Patients and Methods Eligible patients had metastatic prostate cancer threatening enough to justify sustained androgen ablation and were fit enough for chemotherapy. The primary end point was time to castrate-resistant progression as shown by increasing prostate-specific antigen, new radiographic lesions, worsening cancer-related symptoms, or receipt of any other systemic therapy. Results Three hundred six patients were registered; 286 are reported. Median time to progression was 24 months (95% CI, 18 to 39 months) in the standard therapy arm, and 35 months (95% CI, 26 to 44 months) in the chemohormonal group (P = .39). At median follow-up of 6.4 years, overall survival was 5.4 years (95% CI, 4.7 to 7.8 years) in the standard therapy arm versus 6.1 years (95% CI, 5.1 to 10.1 years; P = .41). Prostate-specific antigen kinetics at the time of androgen ablation and the nadir after hormone treatment were strongly correlated with survival. Chemotherapy significantly increased the burden of therapy, with 51% of patients experiencing an adverse event of grade 3 or worse, especially thromboembolic events. Conclusion There is no role for ketoconazole and doxorubicin alternating with vinblastine and estramustine before emergence of a castrate-resistant phenotype.

Effect of Docetaxel in Patients With Hormone-Dependent Prostate-Specific Antigen Progression After Local Therapy for Prostate Cancer

2005 ◽  
Vol 23 (15) ◽  
pp. 3352-3357 ◽  
Author(s):  
Susan Goodin ◽  
Patrick Medina ◽  
Terry Capanna ◽  
Weichung J. Shih ◽  
Sybil Abraham ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Early Stage ◽  
Specific Antigen ◽  
Local Therapy ◽  
Phase Iii ◽  
Early Disease ◽  
Androgen Ablation ◽  
Days Of Therapy ◽  
Psa Progression

Purpose To evaluate docetaxel in the treatment of patients with early-stage prostate cancer with prostate-specific antigen (PSA) progression after local therapy without androgen ablation therapy. Patients and Methods Twenty-five patients with adenocarcinoma of the prostate with PSA progression despite local therapy were treated with 70 mg/m2 docetaxel every 21 days. Treatment was planned for eight cycles. Patients were followed up for effects on PSA, testosterone, and toxicity. Results Twenty-three of 25 patients completed at least one full cycle of therapy. Ten (43%) of 23 patients demonstrated a decrease in PSA by ≥ 50% for at least 4 weeks. The nadir decrease in PSA occurred beyond 150 days of therapy in most patients. Therapy was well tolerated. Grade 4 neutropenia with fever occurred in only six cycles (4.5%). Two patients required 25% dose reductions, both occurring with cycle 6, secondary to increased transaminases in one patient, and grade 3 lacrimation in the other patient. Two patients were removed after the first cycle of therapy due to toxicity (deep venous thrombosis, chest palpitations). Mean testosterone levels were not reduced in 17 patients assessed before and during therapy (P = .12). Conclusion This study demonstrated the activity of docetaxel alone, without androgen ablation, in patients with PSA progression after completion of local therapy. Treatment with docetaxel in this population with early disease progression was well tolerated, biochemically active, and was not androgen ablative. Accrual to national phase III studies in early disease is now critical and should be strongly encouraged to determine the ability of early chemotherapy to improve survival.

Antiandrogen Withdrawal Alone or in Combination With Ketoconazole in Androgen-Independent Prostate Cancer Patients: A Phase III Trial (CALGB 9583)

2004 ◽  
Vol 22 (6) ◽  
pp. 1025-1033 ◽  
Author(s):  
Eric J. Small ◽  
Susan Halabi ◽  
Nancy A. Dawson ◽  
Walter M. Stadler ◽  
Brian I. Rini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progressive Disease ◽  
Specific Antigen ◽  
Phase Iii ◽  
Adrenal Androgen ◽  
Phase Iii Trial ◽  
Androgen Ablation ◽  
Psa Response ◽  
Androgen Levels ◽  
Androgen Independent

Purpose Antiandrogen withdrawal (AAWD) results in a prostate-specific antigen (PSA) response (decline in PSA level of ≥ 50%) in 15% to 30% of androgen-independent prostate cancer (AiPCa) patients. Thereafter, adrenal androgen ablation with agents such as ketoconazole (K) is commonly utilized. The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy. Patients and Methods AiPCa patients were randomized to undergo AAWD alone (n = 132), or together with K (400 mg orally [po] tid) and hydrocortisone (30 mg po each morning, 10 mg po each evening; n = 128). Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K. Results Eleven percent of patients undergoing AAWD alone had a PSA response, compared to 27% of patients who underwent AAWD and simultaneous K (P = .0002). Objective responses were observed in 2% of patients treated with AAWD alone compared to 20% in patients treated with AAWD/K (P = .02). There was no difference in survival. PSA and objective responses were observed in 32% and 7%, respectively, of patients receiving deferred K, and were more common in patients with prior AAWD response. Treatment with K was well tolerated, and resulted in a decline in adrenal androgen levels, which rose at the time of disease progression. Conclusion K has modest activity in AiPCa patients, while AAWD alone has minimal activity. Adrenal androgen levels fall with treatment with K and then climb at the time of progression, suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of K.

Prostate-specific antigen as a measure of disease outcome in metastatic hormone-refractory prostate cancer.

1993 ◽  
Vol 11 (4) ◽  
pp. 607-615 ◽  
Author(s):  
W K Kelly ◽  
H I Scher ◽  
M Mazumdar ◽  
V Vlamis ◽  
M Schwartz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Specific Antigen ◽  
Phase Iii ◽  
Cancer Center ◽  
Hormone Refractory Prostate Cancer ◽  
Data Set ◽  
Hormone Refractory

PURPOSE To evaluate the prognostic significance of pretreatment parameters and posttherapy declines in prostate-specific antigen (PSA) in relation to the survival of patients with hormone-refractory prostate cancer. PATIENTS AND METHODS One hundred ten assessable patients treated on seven sequential protocols at Memorial Sloan-Kettering Cancer Center (MSKCC) for hormone-refractory prostate cancer were evaluated for 29 different pretherapy and posttherapy parameters, including a posttherapy decline in PSA of 50% and 80% from baseline. RESULTS In the univariate analysis, initial Karnofsky performance status (KPS) > or = 80% was associated with a favorable outcome (P = .005), while age, extent of disease on bone scan, and individual sites of metastatic disease were not significant. No difference in survival was observed between patients with measurable or assessable (bone only) disease. Initial hemoglobin (HGB; P = .0012), alkaline phosphatase (ALK; P = .0015), and lactate dehydrogenase (LDH; P = .0002) levels were significant discriminators, while the initial PSA was not. Using a landmark analysis, a significantly longer median survival rate was observed for patients with a > or = 50% decline in PSA (median not reached) versus patients with a less than 50% decline in PSA (median, 8.6 months; P = .0001). Multivariate analysis using the Cox proportional hazards model showed that a > or = 50% decline in PSA (P = .0004) and the natural log of LDH (P = .0001) were the two most significant variables predicting survival. The model was confirmed on an independent data set from the Norwegian Radium Hospital (NRH) in Oslo, Norway. CONCLUSION The results suggest that posttherapy PSA declines can be used as a surrogate end point to evaluate new agents in hormone-refractory prostate cancer. The criteria for response need prospective validation in phase III trials.

Patients’ self-assessment versus investigators’ evaluation in a phase III trial in non-castrate metastatic prostate cancer (GETUG-AFU 15)

2014 ◽  
Vol 50 (5) ◽  
pp. 953-962 ◽  
Author(s):  
Gwenaelle Gravis ◽  
Patricia Marino ◽  
Florence Joly ◽  
Stéphane Oudard ◽  
Franck Priou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Phase Iii ◽  
Self Assessment ◽  
Phase Iii Trial

Clinical Protocol: Phase I Study of an Adenovirus/Prostate-Specific Antigen Vaccine in Men with Metastatic Prostate Cancer

2006 ◽  
Vol 0 (0) ◽  
pp. 060123080936010
Author(s):  
David M. Lubaroff ◽  
Badrinath Konety ◽  
Brian K. Link ◽  
Timothy L. Link ◽  
Tammy Madsen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Prostate Specific Antigen ◽  
Phase I Study ◽  
Metastatic Prostate Cancer ◽  
Specific Antigen ◽  
Clinical Protocol ◽  
Antigen Vaccine
Sign in / Sign up

Export Citation Format

Share Document