Results of a randomized phase II study of irofulven in hormone-refractory prostate cancer patients that have failed first-line docetaxel treatment

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5068-5068
Author(s):  
E. R. Berger ◽  
T. Ciuleanu ◽  
L. Hart ◽  
K. N. Chi ◽  
J. Alexandre ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Median Number ◽  
Hormone Refractory Prostate Cancer ◽  
Antitumor Effects ◽  
Pain Status ◽  
Randomized Phase Ii ◽  
Hormone Refractory ◽  
Grade 3

5068 Background: Currently, no available treatments demonstrate an increase in survival for patients (pts) with hormone- refractory prostate cancer (HRPC) who have failed treatment with docetaxel-based regimens. Previous monotherapy and combination Phase I/II trials with irofulven (IROF) have shown antitumor effects in pts with HRPC, including those with resistance to docetaxel. A randomized phase II study was undertaken in HRPC pts with documented resistance to docetaxel to evaluate the efficacy and safety of IROF regimens compared to mitoxantrone (MITOX). Methods: Pts with metastatic HRPC with documented progression by RECIST or PSA Working Group criteria during or within 3 months of prior docetaxel were randomized to 1 of 3 arms in a 2:2:1 ratio: Arm A: IROF (0.45 mg/kg, Day [D]1, 8 every [q] 3 weeks [w]) and prednisone (PRED; 10 mg qd); Arm B: IROF (0.4 mg/kg D1, 15), capecitabine (CAPE; 2,000 mg/m2 D1–15 q4w) and PRED; Arm C: MITOX (12 mg/m2 q3w) and PRED. Pts were stratified by baseline pain status. Efficacy endpoints included time to progression (TTP), overall survival (OS), and response. Results: Enrollment of 134 treated pts was completed as of Jan 2006 (Arm A/B/C: 53/54/27). Median age: 64/66/63 years, median KPS: 80/90/80, median baseline PSA (ng/mL): 144/136/243, disease-related pain at baseline: 65%/57%/59%, and median number of metastatic sites: 1/1/2. Median pre-study PSA doubling time (days) was 42/44/50. Efficacy: As of Jan 2007, median OS (mos) was 10.1/9.5/7.4 in Arms A/B/C (based on 73% of pt deaths). Preliminary median TTP (mos) was 2.2/3.8/1.8, based mainly on PSA progression. PSA and RECIST responses were 10%/22%/0% and 10%/10%/13%, respectively. Safety: Treatment was well tolerated in all arms. The most frequent Grade 3–4 toxicities (% pts) were asthenia (8%/15%/0%), and vomiting (4%/11%/0%). Grade 3–4 hematological events included neutropenia (22%/15%/61%) and thrombocytopenia (23%/21%/4%). Conclusions: Results to date indicate longer survival, longer TTP, and greater PSA response for IROF/PRED and IROF/CAPE/PRED compared to MITOX/PRED. Based on these data, a larger randomized trial of irofulven in docetaxel resistant HRPC patients is warranted. No significant financial relationships to disclose.

Multicenter Randomized Phase II Study of Two Schedules of Docetaxel, Estramustine, and Prednisone Versus Mitoxantrone Plus Prednisone in Patients With Metastatic Hormone-Refractory Prostate Cancer

2005 ◽  
Vol 23 (15) ◽  
pp. 3343-3351 ◽  
Author(s):  
Stéphane Oudard ◽  
Eugeniu Banu ◽  
Philippe Beuzeboc ◽  
Eric Voog ◽  
Louis Marie Dourthe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Specific Antigen ◽  
Hormone Refractory Prostate Cancer ◽  
Randomized Phase Ii ◽  
Psa Response ◽  
Psa Progression ◽  
Hormone Refractory ◽  
To Receive

Purpose Mitoxantrone-corticosteroid is currently the standard palliative treatment in hormone-refractory prostate cancer (HRPC) patients. Recent clinical trials documented the high activity of the docetaxel-estramustine combination. We conducted a randomized phase II study to evaluate prostate-specific antigen (PSA) response (primary end point) and safety of two docetaxel-estramustine-prednisone (DEP) regimens and mitoxantrone-prednisone (MP). Patients and Methods One hundred thirty metastatic HRPC patients were randomly assigned to receive docetaxel (70 mg/m2 on day 2 or 35 mg/m2 on days 2 and 9 of each 21-day cycle) and estramustine (280 mg PO tid on days 1 through 5 and 8 through 12) or mitoxantrone 12 mg/m2 every 3 weeks; all patients received prednisone (10 mg daily). Results One hundred twenty-seven patients were assessable for PSA response and safety. A ≥ 50% PSA decline was found in a greater percentage of patients in the docetaxel arms (67% and 63%) compared with MP (18%; P = .0001). Median time to PSA progression was five times longer with DEP than with MP (8.8 and 9.3 v 1.7 months, respectively; P = .000001). Overall survival was better in the docetaxel arms (18.6 and 18.4 months) compared with the MP arm (13.4 months), but not significantly so (P = .3). Crossover rates differed significantly among treatment arms (16%, 10%, and 48% in arms A, B, and C, respectively; P = .00001). Treatment-related toxicities were mild and mainly hematologic. Conclusion The results of this randomized phase II study showed significantly higher PSA decline ≤ 50% and longer times to progression in HRPC patients receiving DEP-based chemotherapy than MP, and that DEP could be proposed in this setting.

Combination of LHRH analog with somatostatin analog and dexamethasone versus chemotherapy in hormone-refractory prostate cancer: a randomized phase II study

Urology ◽  
2004 ◽  
Vol 63 (1) ◽  
pp. 120-125 ◽  
Author(s):  
Meletios A. Dimopoulos ◽  
Christos Kiamouris ◽  
Dimitra Gika ◽  
Charalambos Deliveliotis ◽  
Aris Giannopoulos ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Somatostatin Analog ◽  
Hormone Refractory Prostate Cancer ◽  
Randomized Phase Ii ◽  
Hormone Refractory ◽  
Lhrh Analog

Randomized Phase II Study of Two Doses of Gefitinib in Hormone-Refractory Prostate Cancer: A Trial of the National Cancer Institute of Canada-Clinical Trials Group

2005 ◽  
Vol 23 (3) ◽  
pp. 455-460 ◽  
Author(s):  
C.M. Canil ◽  
M.J. Moore ◽  
E. Winquist ◽  
T. Baetz ◽  
M. Pollak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Phase Ii ◽  
National Cancer Institute ◽  
Phase Ii Study ◽  
Hormone Refractory Prostate Cancer ◽  
Randomized Phase Ii ◽  
Rate Of Increase ◽  
Measurable Disease ◽  
Hormone Refractory

Purpose Overexpression of the epidermal growth factor receptor has been demonstrated in advanced prostate cancer and is associated with a poor outcome. A multi-institutional, randomized, phase II study was undertaken by the National Cancer Institute of Canada-Clinical Trials Group to evaluate the efficacy and toxicity of two doses of oral gefitinib in patients with minimally symptomatic, hormone-refractory prostate cancer (HRPC). Patients and Methods Between July and November 2001, 40 patients with HRPC and increasing prostate-specific antigen (PSA) or progression in measurable disease who had not received prior chemotherapy were randomly assigned to 250 mg (n = 19) or 500 mg (n = 21) oral gefitinib daily continuously. The primary end points were PSA response rate and objective measurable response. Functional Assessment of Cancer Therapy Prostate Cancer Subscale (FACT-P) quality-of-life questionnaires were completed at baseline and during treatment. Results None of the patients demonstrated a PSA or objective measurable response. Five (14.3%) of 35 assessable patients had stable PSA (one patient at 250 mg and four patients at 500 mg), and five patients (14.3%) had a best response of stable disease (duration, 2.5 to 16.8 months). No significant effect on the rate of increase in PSA was seen. The most common drug-related nonhematologic toxicities observed were grade 1 to 2 diarrhea (250 mg, 65%; 500 mg, 56%), fatigue (250 mg, 29%; 500 mg, 33%), and grade 1 to 2 skin rash (250 mg, 24%; 500 mg, 39%). FACT-P scores decreased during treatment, indicating worsening of symptoms compared with baseline. Conclusion Gefitinib did not result in any responses in PSA or objective measurable disease at either dose level. Gefitinib has minimal single-agent activity in HRPC.

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