Suramin in hormone-refractory metastatic prostate cancer: a drug with limited efficacy.

1996 ◽  
Vol 14 (5) ◽  
pp. 1626-1636 ◽  
Author(s):  
P J Rosen ◽  
E F Mendoza ◽  
E M Landaw ◽  
B Mondino ◽  
M C Graves ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Peak Plasma ◽  
Specific Antigen ◽  
Rest Period ◽  
High Rate ◽  
Hormone Refractory Prostate Cancer ◽  
Rapid Infusion ◽  
Measurable Disease ◽  
Hormone Refractory

PURPOSE To confirm the previously reported high response rates and prolonged survival in hormone-refractory prostate cancer treated with suramin. PATIENTS AND METHODS Thirty-six eligible patients with hormone-refractory prostate cancer with either measurable disease or bone disease only and a prostate-specific antigen (PSA) level greater than 50 ng/mL were enrolled. Treatment consisted of two 8-week courses of outpatient-based therapy with an interposed rest period. A bayesian adaptive control strategy and a three-compartment pharmacokinetic model that accommodates clearance changes was used to guide individual dosing. A rapid infusion of 1,000 mg/m2 suramin was followed by five daily infusions that targeted 285 micrograms/mL peak plasma levels during the first week. All patients received concomitant hydrocortisone. For the next 7 weeks, patients received one to two doses per week that targeted levels in the 150 to 285 micrograms/mL range and integrated weekly averages of 200 ug/mL. RESULTS Nine patients (28%) had a partial response to suramin based on a > or = 50% decrease in PSA levels coupled with either relief of bone pain or by a 50% decrease in measurable disease. The median overall survival time for all patients is 31 weeks (95% confidence interval [CI], 23 to 51). Treatment was generally well tolerated, with fatigue being the most common significant toxicity, but fatal idiosyncratic myelosuppression (grade V) was observed in one patient. CONCLUSION Using this dosing schedule, suramin has limited activity against hormone-refractory metastatic prostate cancer. Recent data suggest that hydrocortisone administered with suramin may be partly responsible for the benefit attributed to the drug. Although a small cohort of patients appeared to benefit, we were unable to confirm the previously reported high rate of activity and durability of remission using this agent.

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]

Phase II Study of Docetaxel, Estramustine, and Low-Dose Hydrocortisone in Men With Hormone-Refractory Prostate Cancer: A Final Report of CALGB 9780

2001 ◽  
Vol 19 (9) ◽  
pp. 2509-2516 ◽  
Author(s):  
D.M. Savarese ◽  
S. Halabi ◽  
V. Hars ◽  
W.L. Akerley ◽  
M-E Taplin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Low Dose ◽  
Response Rate ◽  
Specific Antigen ◽  
Phase Iii ◽  
Clinical Activity ◽  
Final Report ◽  
Hormone Refractory Prostate Cancer ◽  
Measurable Disease ◽  
Hormone Refractory

PURPOSE: To investigate the combination of docetaxel, estramustine (EM), and low-dose hydrocortisone in men with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Combinations of EM with other antimitotic agents such as docetaxel are synergistic in vitro and show significant clinical activity in patients with HRPC. We studied intravenous administration of docetaxel 70 mg/m2, oral estramustine, and low-dose daily hydrocortisone in men with HRPC who demonstrated progression after initial hormone therapy. RESULTS: Of the 47 men enrolled onto this multicenter cooperative group study, 46 were assessable for response and/or toxicity. In the 24 patients with measurable disease, there were three complete and nine partial responses for a measurable disease response rate of 50% (12 of 24 patients; 95% confidence interval [CI], 27% to 73%). In the 44 patients in whom pretreatment prostate-specific antigen (PSA) was elevated, 30 (68%) had a 50% or greater decrease, and 25 (57%) had a 75% or greater decrease in PSA. The combined measurable disease and biochemical response rate in all 46 assessable patients was 54% (three complete responses, 22 partial responses, 95% CI, 37% to 71%). The predominant toxicity was neutropenia, with 26% of patients having grade 3 and 30% having grade 4 granulocytopenia; there were no episodes of febrile neutropenia. Other common but mild adverse effects included malaise/fatigue, peripheral edema, and hyperglycemia. The incidence of thromboembolic events during therapy was 9%. With a median follow-up of 17 months, the median survival was 20 months. The median time to disease progression was 8 months for all patients, and 10 months for those with measurable disease. CONCLUSION: This therapy is efficacious and moderately well tolerated in HRPC and should be compared in a phase III trial with mitoxantrone and prednisone.

Prostate Cancer: Biology, Incidence, Detection Methods, Treatment Methods, and Vaccines

2020 ◽  
Vol 20 (10) ◽  
pp. 847-854
Author(s):  
Ronald Bartzatt
Keyword(s):  
Prostate Cancer ◽  
Cancer Treatment ◽  
Prostate Specific Antigen ◽  
Cancer Biology ◽  
Early Stage ◽  
Specific Antigen ◽  
Detection Methods ◽  
Hormone Refractory Prostate Cancer ◽  
High Risk Prostate Cancer ◽  
Hormone Refractory

Cancer of the prostate are cancers in which most incidences are slow-growing, and in the U.S., a record of 1.2 million new cases of prostate cancer occurred in 2018. The rates of this type of cancer have been increasing in developing nations. The risk factors for prostate cancer include age, family history, and obesity. It is believed that the rate of prostate cancer is correlated with the Western diet. Various advances in methods of radiotherapy have contributed to lowering morbidity. Therapy for hormone- refractory prostate cancer is making progress, for almost all men with metastases will proceed to hormone-refractory prostate cancer. Smoking cigarettes along with the presence of prostate cancer has been shown to cause a higher risk of mortality in prostate cancer. The serious outcome of incontinence and erectile dysfunction result from the cancer treatment of surgery and radiation, particularly for prostate- specific antigen detected cancers that will not cause morbidity or mortality. Families of patients, as well as patients, are profoundly affected following the diagnosis of prostate cancer. Poor communication between spouses during prostate cancer increases the risk for poor adjustment to prostate cancer. The use of serum prostate-specific antigen to screen for prostate cancer has led to a greater detection, in its early stage, of this cancer. Prostate cancer is the most common malignancy in American men, accounting for more than 29% of all diagnosed cancers and about 13% of all cancer deaths. A shortened course of hormonal therapy with docetaxel following radical prostatectomy (or radiation therapy) for high-risk prostate cancer has been shown to be both safe and feasible. Patients treated with docetaxel-estramustine had a prostate-specific antigen response decline of at least 50%. Cancer vaccines are an immune-based cancer treatment that may provide the promise of a non-toxic but efficacious therapeutic alternative for cancer patients. Further studies will elucidate improved methods of detection and treatment.

Lack of Correlation Between Prostate-Specific Antigen and the Presence of Measurable Soft Tissue Metastases in Hormone-Refractory Prostate Cancer

1996 ◽  
Vol 14 (6) ◽  
pp. 513-517 ◽  
Author(s):  
William D. Figg ◽  
Kara Ammerman ◽  
Nicholas Patronas ◽  
Seth M. Steinberg ◽  
Ronald G. Walls ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Soft Tissue ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Hormone Refractory Prostate Cancer ◽  
Hormone Refractory

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.

Methotrexate and estramustine phosphate in the treatment of hormone-refractory prostatic carcinoma. Preliminary study

1992 ◽  
Vol 59 (1_suppl) ◽  
pp. 151-152
Author(s):  
T. Torelli ◽  
A.M. Bacchioni ◽  
P. Corrada ◽  
G.L. Leidi ◽  
G. Ordesi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostatic Carcinoma ◽  
High Rate ◽  
Hormone Refractory Prostate Cancer ◽  
Estramustine Phosphate ◽  
Number Of Patients ◽  
Low Toxicity ◽  
Preliminary Study ◽  
Hormone Refractory

The authors report preliminary results of a study performed on six patients with by advanced, hormone-refractory prostate cancer. These patients were treated by estramustine phosphate (10 mg/kg) and methotrexate (60 mg/mq). Low toxicity allows the use of this therapy in outpatient regimens. Moreover, the high rate of partial responses (five patients) shows the remarkable efficacy of this therapy, even if follow-up and number of patients are not sufficient to reach definitive conclusions.

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