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.

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.

A phase I open-label, dose escalation study to determine the maximum tolerated dose and to evaluate the safety profile of lenalidomide with every three week docetaxel in subjects with androgen independent prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14618-14618 ◽  
Author(s):  
R. A. Moss ◽  
G. Shelton ◽  
J. Melia ◽  
S. G. Mohile ◽  
D. P. Petrylak
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Dose Escalation ◽  
Specific Antigen ◽  
Maximum Tolerated Dose ◽  
Open Label ◽  
Narcotic Analgesics ◽  
Dose Escalation Study ◽  
Measurable Disease ◽  
Androgen Independent

14618 Background: Based on the known efficacy of docetaxel (D) in Androgen Independent Prostate Cancer (AIPC), and demonstrated activity of the antiangiogenesis agent thalidomide in combination with docetaxel, a Phase I trial in patients (pts) with AIPC with evidence of progression by unidimensionally measurable disease or rising serum Prostate Specific Antigen (PSA) levels after antiandrogen withdrawal was designed. The study evaluates the combination of escalating doses of D and lenalidomide (Ln), a derivative of thalidomide with immunomodulatory and antiangiogenic properties. Pts were permitted to have no more than two prior chemotherapy regimens. Methods: Pts were given D and Ln on a q3 week dose-escalation schedule. Dose Levels of D (mg/m2): Level (L) 1 = 60 L2-L5 =75, given IVPB over 60 minutes in combination with prednisone 5mg po bid. Decadron 20 mg was given 12, 6 hrs and 15 minutes prior to D on D#1. Dose of Ln (mg/day) on D#1–14 of 21-day cycle: L 1 = 10 mg, L2= 10 mg, L3 = 15 mg, L4–20 mg L5 = 25 mg. Patient Characteristics: L1: N = 5. Median Age 66.2 yrs. Median PSA = 101.9 (range 5.9–164.0). Prior CT: none. Prior palliative RT: none. Patients with unidimensionally measurable disease: 4, all in lymph nodes. Patients with bone metastases: 5. Pre-treatment, 1 patient required narcotic analgesics. Results: Five L1 patients are evaluable for toxicity and response. Median number of cycles administered = 4 (range 2–5). Toxicity: There have been no Grade (G) 3 or 4 toxicities. Anti-tumor activity: Two pts (40%) have had a greater than 50% decline in serum PSA on 2 consecutive measurements at least 2 weeks apart. Of 4 pts with unidimensionally measurable disease, all have stable disease by RECIST criteria. Conclusions: At L1, D + Ln has been well tolerated in AIPC. Further dose escalation to L2 and above is planned. [Table: see text]

Suramin and hydrocortisone: determining drug efficacy in androgen-independent prostate cancer.

1995 ◽  
Vol 13 (9) ◽  
pp. 2214-2222 ◽  
Author(s):  
W K Kelly ◽  
H I Scher ◽  
M Mazumdar ◽  
D Pfister ◽  
T Curley ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adaptive Control ◽  
Confidence Interval ◽  
Continuous Infusion ◽  
Advanced Prostate Cancer ◽  
Specific Antigen ◽  
Clinical Activity ◽  
Drug Concentrations ◽  
Measurable Disease ◽  
Androgen Independent

PURPOSE The combination of suramin and hydrocortisone has shown clinical benefit in patients with androgen-independent prostate cancer. Widespread use was limited by the complex dose schedules and the need for pharmacologic monitoring. This study reports three sequential pharmacokinetically derived treatment regimens that simplified the administration of suramin and hydrocortisone with reduced toxicity. PATIENTS AND METHODS Three cohorts of patients with advanced prostate cancer that progressed despite castrate levels of testosterone received oral hydrocortisone plus suramin administered in the following manners: (1) a loading dose of suramin followed by a continuous infusion using an adaptive control program (cohort A); (2) an intermittent schedule using a simplified adaptive control schedule (cohort B); and (3) an empiric dosing regimen (cohort C). Drug concentrations were monitored along with the toxicities associated with each regimen. Efficacy was assessed using measurable-disease criteria, radionuclide scans, and posttherapy changes in prostate-specific antigen (PSA) levels. RESULTS Fifty-six patients were treated and plasma suramin concentrations were similar for each regimen. A partial response was observed in 4% (one of 28; 95% confidence interval, 0% to 18.4%) of patients with measurable disease, while 12% (six of 50; 95% confidence interval, 4.5% to 24.3%) had a greater than 80% decline in the baseline PSA level. The median duration of response was 12 months. No responses on radionuclide scans were seen. Anemia and lymphocytopenia were the most common toxicities, while 7% of patients developed a sensory or motor neurotoxicity. In the sequential regimens, the frequency of renal insufficiency (P = .04) and coagulopathy (P < .0001) decreased, while transaminase elevations (P = .05) were more common using intermittent infusions (cohorts B and C) versus continuous infusion schedules (cohort A). CONCLUSION The administration of suramin was simplified and the drug concentrations were maintained. In this cohort of patients with advanced prostate cancer, the clinical activity of suramin using these dosing schedules was limited. Pharmacodynamic issues, patients selection, and criteria to assess efficacy could have effected the clinical outcome.

Prostate Cancer

2018 ◽  
Author(s):  
Kathryn M. Wilson ◽  
Lorelei Mucci
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Family History ◽  
Prostate Specific Antigen ◽  
Advanced Prostate Cancer ◽  
Advanced Disease ◽  
African Ancestry ◽  
Specific Antigen ◽  
Dietary Factors ◽  
Increased Risk

Prostate cancer is among the most commonly diagnosed cancers among men, ranking second in cancer globally and first in Western countries. There are marked variations in incidence globally, and its incidence must be interpreted in the context of diagnostic intensity and screening. The uptake of prostate-specific antigen screening since the 1990s has led to dramatic increases in incidence in many countries, resulting in an increased proportion of indolent cancers that would never have come to light clinically in the absence of screening. Risk factors differ when studying prostate cancer overall versus advanced disease. Older age, African ancestry, and family history are established risk factors for prostate cancer. Obesity and smoking are not associated with risk overall, but are associated with increased risk of advanced prostate cancer. Several additional lifestyle factors, medications, and dietary factors are now emerging as risk factors for advanced disease.

scholarly journals Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

2016 ◽  
Vol 9 (2) ◽  
pp. 506-515
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vamshi Krishna Muddu ◽  
Vijay Maruti Patil ◽  
Kumar Prabhash
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Retrospective Data Analysis ◽  
Grade 3 ◽  
Named Patient Programme

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27) under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80) and progression-free survival was 2.67 months (1.07–20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

Sign in / Sign up

Export Citation Format

Share Document