Double-Blinded Randomized Study of High-Dose Calcitriol Plus Docetaxel Compared With Placebo Plus Docetaxel in Androgen-Independent Prostate Cancer: A Report From the ASCENT Investigators

2007 ◽  
Vol 25 (6) ◽  
pp. 669-674 ◽  
Author(s):  
Tomasz M. Beer ◽  
Christopher W. Ryan ◽  
Peter M. Venner ◽  
Daniel P. Petrylak ◽  
Gurkamal S. Chatta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Specific Antigen ◽  
Hazard Ratio ◽  
High Dose ◽  
Weekly Docetaxel ◽  
End Point ◽  
Psa Response ◽  
Grade 3 ◽  
Androgen Independent

Purpose To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel. Patients and Methods Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 μg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later. Results Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%). Conclusion This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.

Ixabepilone (Epothilone B Analogue BMS-247550) Is Active in Chemotherapy-Naive Patients With Hormone-Refractory Prostate Cancer: A Southwest Oncology Group Trial S0111

2005 ◽  
Vol 23 (34) ◽  
pp. 8724-8729 ◽  
Author(s):  
Maha Hussain ◽  
Catherine M. Tangen ◽  
Primo N. Lara ◽  
Ulka N. Vaishampayan ◽  
Daniel P. Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Hormone Refractory Prostate Cancer ◽  
Grade 5 ◽  
Psa Response ◽  
Hormone Refractory ◽  
Grade 3

Purpose The epothilones are a new class of tubulin-polymerizing agents with activity in taxane-sensitive and resistant tumor models. We evaluated ixabepilone (BMS-247550) in patients with metastatic hormone-refractory prostate cancer (HRPC). Methods Eligible patients had chemotherapy-naive metastatic HRPC, a Zubrod performance status of 0 to 2, and adequate organ function. All patients received BMS-247550 at 40 mg/m2 over 3 hours every 3 weeks. The primary end point was proportion of patients achieving a prostate-specific antigen (PSA) response. Results Forty-eight patients with metastatic HRPC were registered. Forty-two patients were eligible, with a median age of 73 years and a median PSA level of 111 ng/mL; 78% had bone-only or bone and soft tissue metastases, and 88% had objective radiologic disease progression at registration. Grade 3 and 4 adverse events (AEs) occurred in 16 and three patients, respectively. All grade 4 toxicities were neutropenia or leukopenia. The most frequent grade 3 AEs were neuropathy (eight patients), hematologic toxicity (seven patients), flu-like symptoms, and infection (five patients each). There were no grade 3/4 thrombocytopenia or grade 5 AEs. There were 14 confirmed PSA responses (33%; 95% CI, 20% to 50%); 72% of PSA responders had declines greater than 80%, and two patients achieved an undetectable PSA. The estimated median progression-free survival is 6 months (95% CI, 4 to 8 months), and the median survival is 18 months (95% CI, 13 to 24 months). Conclusion Ixabepilone has demonstrated activity in patients with chemotherapy-naive metastatic HRPC. Major toxicities were neutropenia and neuropathy. Further testing to define its activity relative to standard therapy is warranted.

Response to low-dose ketoconazole and subsequent dose escalation to high-dose ketoconazole in patients with androgen-independent prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4646-4646
Author(s):  
M. Nakabayashi ◽  
W. Xie ◽  
M. M. Regan ◽  
D. M. Jackman ◽  
P. W. Kantoff ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hormonal Therapy ◽  
Dose Escalation ◽  
Low Dose ◽  
Specific Antigen ◽  
High Dose ◽  
Time To Progression ◽  
Subsequent Dose ◽  
Psa Response ◽  
Androgen Independent

4646 Background: High dose ketoconazole (HDK) in combination with steroids has been recognized as an effective secondary hormonal therapy in androgen independent prostate cancer (AIPC). However, HDK causes more severe adverse events than low dose ketoconazole (LDK). Relatively little is known about the efficacy of LDK in AIPC. We evaluated the efficacy of LDK and of subsequent dose escalation from LDK to HDK as secondary hormonal therapy in patients with AIPC. Methods: We retrospectively identified patients with AIPC in a single institution treated with LDK (200 mg PO TID) as secondary hormonal therapy with or without concomitant steroids. Additionally, patients were identified who received dose escalation to HDK (400 mg PO TID) after experiencing a rising prostate-specific antigen (PSA). Results: 138 patients were eligible for the study. Median age was 64 years (range: 41–84); median PSA at initiation of ketoconazole was 37.4 ng/ml (range: 0.8–2279). Patients received LDK as either second (25.4%), third (50.0%) or fourth (21.7%) line hormonal therapy. Thirty-nine of 138 patients (28.3%, 95% CI 20.9%–36.6%) treated with LDK treatment experienced PSA declines ≥50%. Median duration of LDK was 6.4 months in responders and 2.9 months in non-responders. Dose escalation to HDK subsequently was performed in 55 (40%) patients, seven of whom (12.7%) demonstrated a subsequent PSA decline ≥50% (5 LDK responders and 2 LDK non-responders, respectively). Overall time to progression with LDK with or without dose escalation was 3.5 months (range 0.1+–61 months). The most common reversible adverse effect on LDK was grade 1 or 2 fatigue (12.3%). 41.8% of dose escalation group experienced either aggravation or development of toxicities. The most common toxicities on HDK were nausea (16.4%) and fatigue (14.5%). Conclusions: LDK is associated with a PSA response rate comparable to HDK as secondary hormonal therapy in patients with AIPC, and appears to be less toxic. Few patients responded to the dose escalation from LDK to HDK but durable additional responses occurred in some. No significant financial relationships to disclose.

Weekly High-Dose Calcitriol and Docetaxel in Metastatic Androgen-Independent Prostate Cancer

2003 ◽  
Vol 21 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Tomasz M. Beer ◽  
Kristine M. Eilers ◽  
Mark Garzotto ◽  
Merrill J. Egorin ◽  
Bruce A. Lowe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Agent ◽  
Specific Antigen ◽  
High Dose ◽  
Time To Progression ◽  
Oral Hydration ◽  
Phase Ii Studies ◽  
Measurable Disease ◽  
Psa Response ◽  
Androgen Independent

Purpose: To determine the safety and efficacy of weekly high-dose oral calcitriol (Rocaltrol, Roche Pharmaceuticals, Basel, Switzerland) and docetaxel (Taxotere, Aventis Pharmaceuticals, Bridgewater, NJ) in patients with metastatic androgen-independent prostate cancer (AIPC).Patients and Methods: Thirty-seven patients were treated with oral calcitriol (0.5 μg/kg) on day 1 followed by docetaxel (36 mg/m2) on day 2, repeated weekly for 6 weeks of an 8-week cycle. Patients maintained a reduced calcium diet and increased oral hydration. Prostate-specific antigen (PSA) response was the primary end point, which was defined as a 50% reduction in PSA level confirmed 4 weeks later.Results: Thirty of 37 patients (81%; 95% confidence interval [CI], 68% to 94%) achieved a PSA response. Twenty-two patients (59%; 95% CI, 43% to 75%) had a confirmed > 75% reduction in PSA. Eight of the 15 patients with measurable disease (53%; 95% CI, 27% to 79%) had a confirmed partial response. Median time to progression was 11.4 months (95% CI, 8.7 to 14 months), and median survival was 19.5 months (95% CI, 15.3 months to incalculable). Overall survival at 1 year was 89% (95% CI, 74% to 95%). Treatment-related toxicity was generally similar to that expected with single-agent docetaxel. Pharmacokinetics of either calcitriol or docetaxel were not affected by the presence of its companion drug in an exploratory substudy.Conclusion: The combination of weekly oral high-dose calcitriol and weekly docetaxel is a well-tolerated regimen for AIPC. PSA and measurable disease response rates as well as time to progression and survival are promising when compared with contemporary phase II studies of single-agent docetaxel in AIPC. Further study of this regimen is warranted.

Phase II trial of nab-paclitaxel as first-line therapy of hormone refractory metastatic prostate cancer (HRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5152-5152
Author(s):  
T. Kolevska ◽  
C. J. Ryan ◽  
V. Huey ◽  
L. Weisberg ◽  
S. Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Performance Status ◽  
Specific Antigen ◽  
Hematologic Toxicity ◽  
Hormone Refractory Prostate Cancer ◽  
First Line ◽  
Psa Response ◽  
Hormone Refractory ◽  
Grade 3

5152 Background: Many patients with hormone refractory prostate cancer have poor tolerance to treatment. Docetaxel chemotherapy was shown to improve survival but has substantial toxicity, requires steroid administration, may cause poorly reversible neuropathy and requires long infusion times, all limiting its use. Nab-paclitaxel, an albumin-bound nanopaticle form of paclitaxel, delivers paclitaxel without steroids, requires only 30 minutes infusion time and has favorable toxicity profile that may be more tolerable but effective in patients with prostate cancer. The goal of this study was to evaluate the efficacy and toxicity of nab-paclitaxel in first line chemotherapy of men with castration resistant prostate cancer. Methods: nab-paclitaxel was given iv100 mg/m2 weekly x 3 of 4 weeks cycles. Main eligibility criteria include: hormone refractory metastatic prostate cancer, no prior chemotherapy, performance status 0–2. Primary endpoint was efficacy based on prostate-specific antigen (PSA) response. PSA response was PSA decrease of >50%, progressive disease (PD) was PSA increase of >25%, stable disease (SD) was <25% PSA increase or <50% decrease sustained longer that 8 weeks. Results: There are 38 patients enrolled, 35 were evaluable for response. Median age was 71 years old (range 57–86). One patient discontinued the treatment after 1 infusion due to toxicity (elevated ALT). PSA response was seen in 9 (25%) patients and SD in 15 patients (43%), with an overall response rate of 25% and clinical benefit of 68%. Seven patients received treatment for ≥ 6 months with minimal toxicity (range 6–10 months). Grade 3 related hematologic toxicity was reported in 7 (18%) patients (4 anemia, 4 neutropenia), grade 3 related non-hematologic toxicity was reported in 6 patients (1 hypokalemia, 1 muscle weakness, 2 fatigue, 1 fever, 1 neuropathy, 1 ALT elevation). Conclusions: Nab-paclitaxel has activity in patients with metastatic hormone refractory prostate cancer. This regimen was well tolerated, and may be useful in patients who are not suitable candidates for docetaxel based therapy. [Table: see text]

Paclitaxel, Estramustine Phosphate, and Carboplatin in Patients With Advanced Prostate Cancer

2001 ◽  
Vol 19 (1) ◽  
pp. 44-53 ◽  
Author(s):  
William Kevin Kelly ◽  
Tracy Curley ◽  
Susan Slovin ◽  
Glenn Heller ◽  
John McCaffrey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Specific Antigen ◽  
Area Under The Curve ◽  
Complete Response ◽  
Dose Escalation Study ◽  
Time Curve ◽  
Grade 3 ◽  
Safe Dose ◽  
Androgen Independent

PURPOSE: To determine the safety and activity of weekly paclitaxel in combination with estramustine and carboplatin (TEC) in patients with advanced prostate cancer. PATIENTS AND METHODS: In a dose-escalation study, patients with advanced prostate cancer were administered paclitaxel (weekly 1-hour infusions of 60 to 100 mg/m2), oral estramustine (10 mg/kg), and carboplatin (area under the curve, 6 mg/mL-min every 4 weeks). Paclitaxel levels were determined 0, 30, 60, 90, and 120 minutes and 18 hours after infusion, and a concentration-time curve was estimated. Once a safe dose was established, a multi-institutional phase II trial was conducted in patients with progressive androgen-independent disease. RESULTS: Fifty-six patients with progressive androgen-independent disease were treated for a median of four cycles. The dose of paclitaxel was escalated from 60 to 100 mg/m2 without the occurrence of DLT. Posttherapy decreases in serum prostate-specific antigen levels of 50%, 80%, and 90% were seen in 67%, 48%, and 39% (95% confidence interval, 55% to 79%, 35% to 61%, 26% to 52%) of the patients, respectively. Of the 33 patients with measurable disease, two (6%) had a complete response and 13 (39%) had a partial response. The overall median time to progression was 21 weeks, and the median survival time for all patients was 19.9 months. Major grade 3 or 4 adverse effects were thromboembolic disease (in 25% of patients), hyperglycemia (in 38%), and hypophosphatemia (in 42%). Significant leukopenia, thrombocytopenia, and peripheral neuropathy were not observed. CONCLUSION: TEC has significant antitumor activity and is well tolerated in patients with progressive androgen-independent prostate cancer.

Phase I Trial of Docetaxel With Estramustine in Androgen-Independent Prostate Cancer

1999 ◽  
Vol 17 (3) ◽  
pp. 958-958 ◽  
Author(s):  
Daniel P. Petrylak ◽  
Robert B. Macarthur ◽  
John O'Connor ◽  
Gary Shelton ◽  
Timothy Judge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Response Rate ◽  
Area Under The Curve ◽  
Narcotic Analgesics ◽  
Pain Medications ◽  
Psa Response ◽  
Grade 3 ◽  
Recommended Phase Ii Dose ◽  
Androgen Independent

PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated every 21 days. RESULTS: Thirty-four patients were assessable for toxicity and 33 for response. In the MPT patients, dose-limiting myelosuppression was reached at 80 mg/m2, with six patients experiencing grade 3/4 granulocytopenia. In EPT patients, escalation above 70 mg/m2 was not attempted. Fourteen MPT (70%) and six EPT (50%) patients had a ≥ 50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. The overall 50% PSA response rate was 63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a partial response. At the time of entry onto the study, 15 patients required narcotic analgesics for bone pain; after treatment, eight (53%) discontinued their pain medications. The area under the curve for docetaxel increased linearly from 40 to 70 mg/m2. At 80 mg/m2, the measured area under the curve was 8.37 (standard deviation, 0.724), which was significantly higher than the previously reported values. CONCLUSION: The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.

Phase II study of intravenous vinorelbine plus hormone therapy in hormone-refractory prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14601-14601
Author(s):  
E. Silva ◽  
F. Silva
Keyword(s):  
Prostate Cancer ◽  
Elderly Patients ◽  
Prostate Specific Antigen ◽  
Phase Ii ◽  
Performance Status ◽  
Specific Antigen ◽  
Hormone Refractory Prostate Cancer ◽  
Phase Ii Studies ◽  
Hormone Refractory ◽  
Grade 3

14601 Background: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in Phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. The purpose of this study was the investigation of the efficacy of vinorelbine and its toxicity. Methods: Patients with metastatic prostate cancer, progressive after hormonal therapy, receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day. Previous chemotherapy was allowed if stopped 6 months before. 44 received VRL according to the protocol. Inclusion criteria: hormone refractory prostate cancer patients PSA >20; performance status WHO < 2. The primary endpoint was prostate specific antigen (PSA) levels, pain, and WHO performance status. Their mean (range) age was 71 (45–80) years, their median prostate specific antigen (PSA) level was 286 (38–950) ng/ml, and the median Gleason score was 8 (7 to 9). 38 patients had had previous chemotherapy. Results: Among the 44 patients, 7 with less than 3 cycles were not evaluated. Patients received a mean (range) of 9 (3–44) cycles of therapy. 6 patients (14%) had not been dispensed prior chemotherapy and 38 (86%) had; 19 (43%) had 2 lines of chemotherapy and 19 (43%) had 1 line. The median follow-up was 13 months. There were no reported drug related Grade 3 toxicities. Only 2 patients required a blood transfusion. Tumour responses: 7 (16%); 17 (39%) PSA stable; 13 (29%) PSA progression, 7 not evaluated. Time of PSA response was 7 months; time to progression: 7 months. Conclusions: Vinorelbine (VRL) is a safe regimen in previous poly-chemotherapy treated hormone-refractory prostate cancer elderly patients and even with response and efficacy. No significant financial relationships to disclose.

Randomized phase II trial of docetaxel, with or without doxercalciferol, in advanced, androgen-independent prostate cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5119-5119
Author(s):  
S. Attia ◽  
J. Eickhoff ◽  
G. Wilding ◽  
J. Blank ◽  
H. Rezazadeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Double Blind ◽  
Vitamin D Analogs ◽  
Psa Response ◽  
Androgen Independent

5119 Background: Docetaxel is the standard of care for advanced androgen-independent prostate cancer (AIPC). Doxercalciferol, a vitamin D analog (1a-hydroxyvitamin D2), has single-agent activity in AIPC (Clin Cancer Res 9(11), 2003). Preclinical evidence supports combining vitamin D with chemotherapy to treat AIPC. Here we report results of a multi-institutional trial combining docetaxel and doxercalciferol. Methods: Patients with chemo-naive AIPC were randomized 1:1 to receive, on a four week cycle, docetaxel (35 mg/m2 IV; days 1, 8 and 15) with either doxercalciferol (10 mcg PO daily, days 1–28) or placebo in a double-blind fashion. The primary endpoint was to compare progression-free survival (PFS). Secondary endpoints were to assess overall survival (OS), objective response (RECIST), PSA response (consensus criteria), and toxicity. PFS and OS were analyzed on an intent-to-treat basis. Eligibility criteria included no prior cytotoxic therapy; radiographic evidence of metastasis; performance status ≤ 2 and no recent history of nephrolithiasis. Results: Seventy patients were randomized. Median follow-up time was 16.2 months (range, 0–40.5 months). Median PFS in the doxercalciferol arm was 14.9 months (95% CI: 8.7–16.6 months) versus 11.9 months (95% CI: 8.9–16.4 months) in the placebo arm (p=0.73). Median OS in the doxercalciferol arm was 18.1 months (95% CI: 14.9–26.2 months) and 17.9 months (95% CI: 12.1–24.6 months) in the placebo arm (p=0.63). Twenty-nine patients in the doxercalciferol arm and 33 in the placebo arm were evaluable for objective response. No complete responses were seen. Partial response rate was 14% (doxercalciferol) vs. 15% (placebo) (p=0.88). PSA response rate was 44% (95% CI: 29%-60%) in the doxercalciferol arm and 42% (95% CI: 27%-59%) in the placebo arm (p=0.87). Grade 3/4 toxicity rates were 38% in the doxercalciferol arm and 39% in the placebo arm (p=0.99). Conclusions: Despite encouraging data with other vitamin D analogs combined with docetaxel in AIPC, the addition of daily doxercalciferol to weekly docetaxel did not enhance median PFS, OS or tumor response. Toxicity was similar between treatment groups. Further evaluation of vitamin D analogs in combination with chemotherapy in AIPC remains of interest. No significant financial relationships to disclose.

Prognostic value of free testosterone (FT) levels during salvage chemotherapy with carboplatin plus weekly docetaxel in metastatic castration- and docetaxel-resistant prostate cancer (mDRPC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 152-152
Author(s):  
Christoph W. Reuter ◽  
Michael A. Morgan ◽  
Martin Fenner ◽  
Viktor Grünwald ◽  
Arnold Ganser
Keyword(s):  
Prostate Cancer ◽  
Disease Progression ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Free Testosterone ◽  
Salvage Chemotherapy ◽  
Blood Levels ◽  
Weekly Docetaxel ◽  
Grade 3 ◽  
The Impact

152 Background: Recent data suggest that carboplatin plus weekly docetaxel (DC) may be effective in mDRPC. Carboplatin, docetaxel and steroids interfere with testosterone biosynthesis and/or metabolism. In this study the impact of DC treatment on testosterone blood levels was analyzed. Methods: Docetaxel failure/resistance was defined as disease progression during docetaxel treatment according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 74 consecutive DRPC patients (pts.) were treated with at least 2 cycles of carboplatin AUC5 iv for 30 min on day 1 plus docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) every 4 weeks and prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. FT levels were measured before (n=50) and during DC chemotherapy (n=43). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 35/74 (47.3%) pts. At the current analysis the median follow-up time was 16.0 months and 54/74 pts. had died. Median progression-free survival (PFS) was 6.9 months (CI 95% 5.3, 8.4) and median overall survival (OS) was 18.6 months (CI 95% 12.4, 24.7). Median nadir FT levels were 2.8 pmol/L before and below the RIA detection limit of 0.6 pmol/L during DC treatment (p=0.011). While only 4/50 pts. had FT levels <0.6 pmol/L before DC treatment (all under abiraterone therapy), 27/43 pts. had nadir FT values <0.6 pmol/L during DC chemotherapy (p<0.001). FT levels <1 pmol/L during DC treatment were associated with a higher PSA response rate (hazard ratio HR 0.09; CI 0.02, 0.81, p=0.032) and FT levels <0.6 pmol/L with a higher OS (HR 0.45; CI 0.18, 0.98, p=0.045). FT remained statistically prognostic in multivariable analyses. The DC regimen was reasonably well tolerated, with leukopenia/ neutropenia as the most common reversible grade 3/4 toxicity (41.9/37.8%). Conclusions: These data demonstrate for the first time that FT is an important prognostic factor for PSAR and OS in mDRPC pts. receiving chemotherapy.

scholarly journals SWOG S0925: A Randomized Phase II Study of Androgen Deprivation Combined With Cixutumumab Versus Androgen Deprivation Alone in Patients With New Metastatic Hormone-Sensitive Prostate Cancer

2015 ◽  
Vol 33 (14) ◽  
pp. 1601-1608 ◽  
Author(s):  
Evan Y. Yu ◽  
Hongli Li ◽  
Celestia S. Higano ◽  
Neeraj Agarwal ◽  
Sumanta K. Pal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Relative Risk ◽  
Specific Antigen ◽  
Xenograft Model ◽  
Patient Characteristics ◽  
Circulating Tumor Cell ◽  
Androgen Deprivation ◽  
End Point ◽  
Psa Response ◽  
Hormone Sensitive

Purpose Cixutumumab, formerly IMC-A12, is a recombinant human monoclonal immunoglobulin G1 antibody that targets insulin-like growth factor I receptor (IGF-IR). Cixutumumab was synergistic with castration in a hormone-sensitive prostate cancer xenograft model. Patients and Methods Patients with new metastatic prostate cancer were randomly assigned within 30 days of initiating androgen deprivation (AD) to cixutumumab added to a luteinizing hormone–releasing hormone agonist with bicalutamide versus AD alone. With 180 patients and one-sided alpha of 0.10, there would be 90% power to detect an absolute 20% difference in undetectable prostate-specific antigen (PSA; ≤ 0.2 ng/mL) rate at 28 weeks (relative risk, 1.44); this end point was previously strongly correlated with survival. Secondary end points included the proportion of patients with PSA > 4.0 ng/mL, safety and tolerability, circulating tumor cell (CTC) levels, and seven plasma IGF-IR biomarkers. Fisher's exact test was used for the primary end point, and extended Mantel-Haenszel χ2 test was used for three PSA response categories. Results The trial accrued 210 eligible patients (105 randomly assigned to each arm). Patient characteristics were similar in both arms. Undetectable PSA rate was 42 (40.0%) of 105 for cixutumumab plus AD and 34 (32.3%) of 105 for AD alone (relative risk, 1.24; one-sided P = .16). Lower baseline CTCs (0 v 1 to 4 v ≥ 5/7.5 mL whole blood) were associated with higher rate of PSA response (three categories; P = .036) in 39 evaluable patients. IGF-IR biomarkers were not correlated with PSA outcome, and cixutumumab did not significantly change these biomarker levels. Conclusion Cixutumumab plus AD did not significantly increase the undetectable PSA rate in men with new metastatic hormone-sensitive prostate cancer. CTCs at baseline may carry prognostic value.

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