Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate.

1994 ◽  
Vol 12 (10) ◽  
pp. 2005-2012 ◽  
Author(s):  
K J Pienta ◽  
B Redman ◽  
M Hussain ◽  
G Cummings ◽  
P S Esper ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Soft Tissue ◽  
Median Survival ◽  
Performance Status ◽  
Specific Antigen ◽  
Complete Response ◽  
Experimental Models ◽  
Survival Duration ◽  
Median Survival Duration ◽  
Hormone Refractory

PURPOSE Estramustine and etoposide (VP-16) have been demonstrated to inhibit the growth of prostate cancer cells in experimental models. This led us to evaluate the effectiveness of this combination in the treatment of patients with metastatic prostate carcinoma refractory to hormone therapy. PATIENTS AND METHODS Estramustine 15 mg/kg/d and VP-16 50 mg/m2/d, were administered orally in divided doses for 21 days. Patients were then taken off therapy for 7 days and the cycle then repeated. Therapy continued until evidence of disease progression. RESULTS Forty-two patients have been enrolled onto this trial with a minimum of 40 weeks follow-up. Of 18 patients with measurable soft tissue disease, three demonstrated a complete response (CR) and six a partial response (PR) for longer than 2 months. Of these 18 patients, pretreatment prostate-specific antigen (PSA) levels decreased by at least 75% in five men (28%) and by at least 50% in nine (50%). The median survival duration has not been reached in those patients who demonstrated a response either by soft tissue or PSA criteria. Of 24 patients with disease limited to bone, six (25%) demonstrated improvement and nine (38%) demonstrated stability in their bone scans. Five men (21%) demonstrated a decrease of at least 75% in pretreatment PSA levels and 14 (58%) demonstrated at least a 50% decrease; the median survival duration has not been reached in these patients. Pretreatment performance status is an important predictor of survival. CONCLUSION We conclude that the combination of estramustine and VP-16 is an active oral regimen in hormone-refractory prostate cancer.

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

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.

Simple prognostic model to predict survival in patients with undifferentiated carcinoma of unknown primary site.

1995 ◽  
Vol 13 (7) ◽  
pp. 1720-1725 ◽  
Author(s):  
A van der Gaast ◽  
J Verweij ◽  
A S Planting ◽  
W C Hop ◽  
G Stoter
Keyword(s):  
Alkaline Phosphatase ◽  
Prognostic Factors ◽  
Median Survival ◽  
Performance Status ◽  
Primary Site ◽  
Survival Duration ◽  
Unknown Primary ◽  
Unknown Primary Site ◽  
Carcinoma Of Unknown Primary ◽  
Median Survival Duration

PURPOSE We performed this study to identify prognostic factors in a subgroup of patients with carcinoma of unknown primary site treated with cisplatin combination chemotherapy. PATIENTS AND METHODS Seventy-nine patients with poorly differentiated adenocarcinoma or undifferentiated carcinoma of unknown primary site were treated on two consecutive phase II chemotherapy protocols. The first protocol consisted of treatment with 3-week courses of cisplatin, etoposide, and bleomycin (BEP). In the second protocol, cisplatin was administered weekly combined with oral administration of etoposide (DDP/VP). To identify prognostic factors, univariate and multivariate analyses were conducted. RESULTS In the univariate analysis, performance status, histology, liver or bone metastases, and serum levels of alkaline phosphatase and AST were significant variables to predict survival. In the multivariate analysis, performance status and alkaline phosphatase were the most important prognostic factors. CONCLUSION Good-prognosis patients had a performance score of 0 (World Health Organization [WHO]) and an alkaline phosphatase serum level less than 1.25 times the upper limit of normal (N). These patients had a median survival duration greater than 4 years. Intermediate-prognosis patients were characterized by either a WHO performance status < or = 1 or an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of 10 months and a 4-year survival rate of only 15%. The poor-prognosis group had both a WHO performance status > or = 1 and an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of only 4 months and none survived beyond 14 months. Treatment strategies for these three groups are discussed. It is suggested that this prognostic model be validated in other patients series.

A multivariate prognostic nomogram incorporating PSA kinetics in hormone-refractory metastatic prostate cancer (HRPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5058-5058
Author(s):  
M. Eisenberger ◽  
E. S. Garrett-Mayer ◽  
Y. Ou Yang ◽  
R. de Wit ◽  
I. Tannock ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Factors ◽  
Median Survival ◽  
Cox Model ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Tumor Grade ◽  
Multivariate Model ◽  
Psa Kinetics ◽  
Hormone Refractory

5058 Background: To develop a prognostic model and nomogram using baseline clinical variables to predict death among men with metastatic hormone-refractory prostate cancer (HRPC). Methods: TAX 327 was a clinical trial that randomized 1,006 men with metastatic HRPC to receive 3-weekly or weekly docetaxel or mitoxantrone, each with prednisone. Of these, 635 men had baseline data that included PSA kinetics, with 518 mortality events recorded as of November 2006. We developed a multivariate Cox model and nomogram to predict survival at two, three, and five years. Results: Ten independent prognostic factors were identified in multivariate analysis and include: 1) presence of liver metastases (HR 1.64, p=0.02), 2) number of metastatic sites (HR 1.58 if =2 sites, p=0.001), 3) clinically significant pain at baseline (HR 1.46, p<0.0001), 4) Karnofsky Performance Status (HR 1.42 if =70, p=0.01), 5) type of progression at baseline (HR 1.40 for measurable disease progression and 1.28 for bone scan progression, p=0.002 and 0.014 respectively), 6) pretreatment PSA doubling time (PSADT, HR 1.20 if <55 days, p=0.048), 7) baseline PSA (HR 1.17 per log rise, p<0.0001), 8) tumor grade (HR 1.18 for high grade, p=0.076), 9) alkaline phosphatase (HR 1.26 per log rise, p<0.0001), and 10) hemoglobin (HR 1.10 per unit decline, p=0.006). A PSADT <55 days (median value for this dataset) was associated with other adverse prognostic factors, but was independently associated with shortened overall survival. Men with a PSA less than the median of 114 ng/ml and longer PSADT (=55 days) had a median survival of 24.7 months, while those with higher PSA and shorter PSADT had a median survival of 13.8 months. A nomogram was developed based on this Cox multivariate model and validated internally using bootstrap methods, with a concordance index of 0.69. Conclusions: This multivariate model identified several prognostic factors in men with metastatic HRPC including PSADT, and led to the successful development of a clinically applicable nomogram. External prospective validation may support the wider use of this prognostic baseline model for men with HRPC treated with chemotherapy. No significant financial relationships to disclose.

Polyamine-reduced diet in metastatic hormone-refractory prostate cancer (HRPC) patients

2003 ◽  
Vol 31 (2) ◽  
pp. 384-387 ◽  
Author(s):  
B. Cipolla ◽  
F. Guillé ◽  
J.-P. Moulinoux
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Specific Antigen ◽  
World Health Organisation ◽  
World Health ◽  
Hormone Refractory Prostate Cancer ◽  
Cancer Specific Survival ◽  
Pain Status ◽  
Intestinal Decontamination ◽  
Hormone Refractory

Polyamine (PA) deprivation is effective in prostate carcinoma models. We have assessed the observance by patients, tolerance and side effects of a PA-reduced diet (PRD) and intestinal decontamination (ID), in order to reduce PA dietary and intestinal bacterial pools, in metastatic, hormone-refractory prostate cancer (HRPC) patients. A total of 13 volunteers (mean age, 67±10 years) with metastatic HRPC were proposed for PRD and ID (0.75 g/day of oral neomycin every other week). The mean time from HRPC diagnosis to the start of the diet was 12±8 months. Of the total 13, seven patients had received prior chemotherapy or Estramustine phosphate. PRD was obtained after HPLC assessment of PA contents in current foods and given 5 days a week. Toxicity, performance and pain status were assessed according to the World Health Organisation and EORTC scales. Prostatic specific antigen (PSA), blood counts, ionograms, transaminases and erythrocyte PA spermidine (Spd) and spermine (Spm; assessed by HPLC) were evaluated regularly. Mean observance was 8±7 months (range, 2–26 months). One case of grade II toxicity to neomycin was observed. Cancer-specific survival (after the diet) was 14±7 months, and two patients are still alive. All the other patients have died of their cancer at 12±6 months (range, 4–20 months). Cancer-specific survival after hormonal escape was 27±11 months (range, 9–45 months). Performance status was improved during the regimen and deteriorated 3 months after stopping. Pain score was improved (1.3 versus 0.6; P=0.04) during the diet and increased (2.1 versus 0.3) 3 months after stopping. Erythrocyte Spd (11.6±7 versus 7.7±2 nmol/8×109 erythrocytes; P=0.036) and Spm (7±6 versus 3.9±1.6 nmol/8×109 erythrocytes; P=0.036) levels were significantly reduced at 3 months. One patient had a >50% reduction in PSA, three patients had PSA stabilization for 6 months. PSA progression was observed in all other patients. No significant modification of other studied biological parameters was noted. Reducing PA dietary intake and ID is a well-observed and tolerated regimen and seems to be beneficial for patient quality of life and pain control. Patients with low initial PSA can experience durable stabilization. These encouraging results in such an aggressive disease certainly warrant further investigation.

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.

Importance of continued testicular suppression in hormone-refractory prostate cancer.

1993 ◽  
Vol 11 (11) ◽  
pp. 2167-2172 ◽  
Author(s):  
C D Taylor ◽  
P Elson ◽  
D L Trump
Keyword(s):  
Prostate Cancer ◽  
Weight Loss ◽  
Performance Status ◽  
Survival Duration ◽  
Hormone Refractory Prostate Cancer ◽  
Androgen Ablation ◽  
Systemic Treatments ◽  
Disease Site ◽  
Androgen Suppression ◽  
Hormone Refractory

PURPOSE Patients in whom prostate cancer progresses despite testicular androgen ablation are generally said to have cancers that have become resistant to hormonal maneuvers. If androgen suppression has been pharmacologic, this therapy is often stopped before consideration of other systemic treatments. This exploratory study sought clinical correlates of experimental evidence that there may be substantial acceleration of tumor growth after cessation of androgen suppression. MATERIALS AND METHODS A retrospective multivariate analysis was performed on survival data for 341 patients treated on four clinical trials of secondary therapy for hormone-refractory prostate cancer. Factors included in the model were recent weight loss, age, performance status, disease site (soft tissue v bone-dominant), prior radiotherapy, and continued androgen suppression v discontinued exogenous endocrine therapy. RESULTS Recent weight loss, age, performance status, and disease site were important prognostic factors for survival duration in hormone-refractory prostate cancer. Correcting for these factors, continued testicular androgen suppression was also an important predictor of survival duration in all data sets examined. CONCLUSION This retrospective study showed a modest advantage in survival duration for men with hormone-refractory prostate cancer who continued to receive testicular androgen suppression. The hypothesis that continued hormonal maneuvers can still affect survival in this group warrants examination in prospective trials.

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 trial of 96-hour paclitaxel plus oral estramustine phosphate in metastatic hormone-refractory prostate cancer.

1997 ◽  
Vol 15 (9) ◽  
pp. 3156-3163 ◽  
Author(s):  
G R Hudes ◽  
F Nathan ◽  
C Khater ◽  
N Haas ◽  
M Cornfield ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Specific Antigen ◽  
Complete Response ◽  
Hormone Refractory Prostate Cancer ◽  
Estramustine Phosphate ◽  
Clinical Criteria ◽  
Hormone Refractory ◽  
Hormonal Therapies

PURPOSE To evaluate the antitumor activity of 96-hour paclitaxel and daily oral estramustine phosphate (EMP) in patients with metastatic hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS Thirty-four patients with adenocarcinoma of the prostate that progressed after one or more hormonal therapies and a trial of antiandrogen withdrawal were enrolled onto this phase II trial. Patients received paclitaxel 120 mg/m2 by 96-hour intravenous (i.v.) infusion on days 1 through 4 of each 21-day cycle, together with daily oral EMP 600 mg/m2/d, continuously. RESULTS Four of nine patients with measurable disease had objective responses (one complete response [CR] and three partial responses [PRs]) in liver (two patients) or nodes (two patients) of 2, 6, 8, and 20 months' duration. Of 25 assessable patients with metastases limited to bone, 14 had a > or = 50% decline in pretreatment prostate-specific antigen (PSA) level sustained for at least 6 weeks and seven had a > or = 80% decline. Overall, 17 of 32 patients (53.1%) with elevated pretreatment PSA levels had a > or = 50% decline of PSA and nine (28.1%) had a > or = 80% decrease. The main toxicities (> or = grade 2) were nausea, fluid retention, and fatigue, which occurred in 33%, 33%, and 24.2% of patients. Median time to progression, based on increasing PSA level and other clinical criteria, was 22.5 weeks. The estimated median overall survival time is 69 weeks. CONCLUSION The combination of EMP and 96-hour paclitaxel is an active regimen for patients with HRPC. These results further support the therapeutic strategy of combining agents that impair microtubule function by complementary mechanisms.

Phase II study of hepatic arterial floxuridine, leucovorin, and dexamethasone for unresectable liver metastases from colorectal carcinoma.

1994 ◽  
Vol 12 (11) ◽  
pp. 2288-2295 ◽  
Author(s):  
N Kemeny ◽  
J A Conti ◽  
A Cohen ◽  
P Campana ◽  
Y Huang ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Median Survival ◽  
Response Rate ◽  
Survival Rates ◽  
Hepatic Metastases ◽  
Hepatic Arterial Infusion ◽  
Complete Response ◽  
Survival Duration ◽  
Median Survival Duration ◽  
Biliary Sclerosis

PURPOSE To determine the toxicity, response rate, and survival of a regimen of hepatic arterial floxuridine (FUDR) with leucovorin (LV) and dexamethasone (Dec) for the treatment of unresectable hepatic metastases from colorectal carcinoma. PATIENTS AND METHODS Sixty-two patients with hepatic metastases (33 previously untreated with chemotherapy) were treated with FUDR (0.30 mg/kg/d) and LV (15 mg/m2/d) and Dec (20 mg total dose) as a 14-day hepatic arterial infusion via an implantable pump alternating with 2 weeks of saline. RESULTS The complete response (CR) plus partial response (PR) rate was 78% in previously untreated patients, with a median survival duration of 24.8 months; 1- and 2-year survival rates were 91% and 57%, respectively. In the previously treated group, the response rate was 52%, with a median survival duration of 13.5 months. Only 3% of patients (two of 62) developed biliary sclerosis; this was significantly lower than the 21% biliary sclerosis rate observed in our previous trial of hepatic arterial FUDR and LV without Dec (P = .002). CONCLUSION The addition of Dec to hepatic arterial FUDR and LV reduces biliary toxicity while maintaining an excellent response rate and survival. We recommend that this treatment be studied further.

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