Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007112 (prostatic adenocarcinoma)
 2,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The unavailability of effective treatment of metastatic hormone refractory prostatic carcinoma warrants trials of new and promising treatments. Coumarin is an investigational new drug that has produced objective tumor regression in some patients with metastatic renal cell carcinoma and malignant melanoma. Coumarin has shown activity against prostatic carcinoma in the Dunning R-3327 rat prostatic adenocarcinoma model. Forty-eight patients with metastatic hormone naive (5 stage D1 and 10 stage D2) or hormone refractory (33 stage D3) prostatic carcinoma of average age 67.6 years (range 46-86) and ECOG performance status of 2 or better were given 3 grams coumarin daily by mouth and evaluated monthly for toxicity and response by rigid criteria in a multicenter trial. Toxicity was limited to asymptomatic SGOT elevations in 3 patients and nausea and vomiting in 4 patients that required cessation of therapy in 2. Eligibility and protocol violations removed 6 additional patients from response evaluation. There were no complete responses. Partial responses (3 of 40 patients, 8%) occurred in 2 patients with bidimentionally measurable disease and 1 patient with disease evaluable by bone scan and elevated prostate specific antigen and prostatic acid phosphatase. The remaining patients progressed after 1 to 12 (average 4.4) months. Coumarin is a relatively nontoxic drug that may warrant further trials in a subset of patients with prostatic carcinoma.
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PMID:Phase II evaluation of coumarin (1,2-benzopyrone) in metastatic prostatic carcinoma. 154 51

In patients with metastatic hormone-relapsed adenocarcinoma of the prostate, adriamycin was compared to 5-fluorouracil in a randomized trial in 99 patients and adriamycin alone was studied in an open trial in 48 patients. Response to adriamycin was superior as judged by response of measurable disease (25 vs 8%; P less than 0.05) and survival (median 29 vs 24 weeks; Cox analysis, P less than 0.03), but comparable as judged by acid phosphatase response. Ambulatory status and site of metastases influenced rate of response to chemotherapy. Activity level, site of metastases, weight loss, and the symptom of protein aversion were prognostic factors for survival. Hematologic and gastrointestinal toxicity were frequent but were tolerated satisfactorily. Adriamycin therapy may be beneficial in patients with prostatic cancer after hormone therapy.
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PMID:A comparative clinical trial of adriamycin and 5-fluorouracil in advanced prostatic cancer: prognostic factors and response. 634 81

Intravenous doxorubicin (30 to 60 mg. per m.2 every 3 weeks) was administered to 52 patients with metastatic adenocarcinoma of the prostate, including 41 with bidimensionally measurable soft tissue lesions. Prior therapy in the measurable disease group included hormonal manipulation in 39 cases, irradiation in 39 and cytotoxic drugs in 19. In 39 of 41 adequately treated patients with soft tissue lesions only 2 (5 per cent, 95 per cent confidence limits 0 to 12 per cent) achieved a partial remission for 12 and 6 months, respectively, 3 had a minor response for 5, 4 and 3 months, respectively, and 1 had stabilization of disease for 4 months. Survival in this group was 16 months versus 5 months for patients with a mixed response and progression of disease. Of 11 patients with evaluable parameters only 1 had stabilization and 5 showed subjective improvement. Recognizing the patient selection bias and treatment schedule in this study, we believe that doxorubicin has marginal activity in soft tissue lesions in patients with advanced prostatic cancer.
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PMID:Phase II trial of doxorubicin in bidimensionally measurable prostatic adenocarcinoma. 637 69

Menogaril, a semisynthetic anthracycline antibiotic, was administered to patients with metastatic adenocarcinoma of the prostate. Forty-five patients with measurable disease and 45 patients with evaluable disease received 150-200 mg/m2 over 1 hour every 28 days. There were three partial responses (PR) among 87 patients evaluable for response. Myelosuppression was dose limiting. There were two deaths related to leukepenia. Other toxicities included phlebitis, alopecia, nausea and vomiting. One patient developed acute nonlymphocytic leukemia. Menogaril at these doses and schedule is toxic and has no significant antitumor activity in metastatic adenocarcinoma of the prostate.
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PMID:Phase II trial of menogaril in metastatic adenocarcinoma of the prostate. A Southwest Oncology Group study. 796 Jun 10

Based upon prior data suggesting that alpha-interferon possesses chemomodulatory activity, the Southwest Oncology Group conducted a study in which patients with hormone refractory, metastatic (stage D2) adenocarcinoma of the prostate were treated with 5-fluorouracil (5-FU) and Roferon-A. All patients had bidimensionally measurable disease. Treatment consisted of 5-FU 750 mg/m2/day by continuous i.v. infusion for 5 days with Roferon-A 9 million units subcutaneously ono days 1, 3 and 5. Roferon-A was continued three times weekly throughout treatment. Following a one week hiatus from 5-FU (week 2), 5-FU was continued at a dose of 750 mg/m2 i.v. bolus weekly. Nineteen patients were evaluable for toxicity. The most common toxicities were gastrointestinal and mucosal, hematologic and a flu-like syndrome. There were no deaths related to treatment. Among the 14 patients evaluable for response, the response rate was 0% (95% confidence interval, 0-18%). Thirteen of the 19 evaluable patients have died with a median survival of 9 months. The combination of 5-FU and Roferon-A does not have sufficient activity against advanced, hormone refractory prostate cancer to warrant further investigation.
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PMID:Treatment of stage D2 hormone refractory carcinoma of the prostate with 5-fluorouracil and Roferon-A: a Southwest Oncology Group study. 1085 28

Twenty-nine patients with progressive hormone-refractory metastatic adenocarcinoma of the prostate were treated with daily estramustine phosphate at 10 mg/kg, and I.V. doxorubicin 50 mg/m2 every 3 weeks. Twenty-six patients were evaluable. Four of seven patients with nonosseous measurable disease had partial responses lasting 3 to 10 months. Eleven of 19 patients with osseous metastases had stable disease or improvement on bone scan, 6 of these for 7 months or longer. Median time to progression was 20 weeks, and the median survival was 43 weeks.
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PMID:Phase II pilot study of combined chemohormonal therapy with doxorubicin and estramustine in metastatic prostate cancer. 1120 3

Recent studies of docetaxel have demonstrated improved survival over mitoxantrone and prednisone in patients with hormone-refractory prostate cancer (HRPC), supporting the study of novel docetaxel-containing regimens as primary therapy or following initial docetaxel-based therapy. To evaluate the combination of docetaxel and vinorelbine in the treatment of patients with HRPC, 40 patients with proven adenocarcinoma of the prostate with progressive metastatic disease despite androgen ablation were enrolled onto this phase II trial. Patients were treated with docetaxel 60 mg/m2 on day 1 and vinorelbine 15 mg/m2 on days 1 and 8 of a 21-day cycle. All patients received dexamethasone 8 mg twice daily for 4 days starting 1 day prior to the docetaxel infusion. After the first three patients were enrolled, filgrastim was added on days 2-6 and 9-13. Of the 40 patients enrolled, 19 had no prior chemotherapy and 21 had received at least one prior chemotherapy regimen. Of the 19 patients without prior chemotherapy and the 21 with prior chemotherapy, 7 (37%) and 6 (29%) , respectively, demonstrated a decrease in prostate specific antigen by > 50% maintained for at least 4 weeks. Out of eight patients with measurable disease, one achieved a partial response and four demonstrated stable disease. There was one patient with deep vein thrombosis, and febrile neutropenia was noted in only three patients after the protocol was modified to include filgrastim support. The combination of docetaxel and vinorelbine with filgrastim was well tolerated and active against HRPC in patients with or without prior chemotherapy.
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PMID:A phase II trial of docetaxel and vinorelbine in patients with hormone-refractory prostate cancer. 1583 57

Taxanes remain the only agents to extend survival in castration-resistant metastatic prostate cancer, but their impact on the natural history of this disease is modest. We sought to test the hypothesis that increased delivery of taxane chemotherapy to the tumor through the use of a macromolecular polymer-drug conjugate of paclitaxel modulated by estradiol could extend the utility of this class of drugs. Patients with metastatic adenocarcinoma of the prostate who progressed despite standard hormonal therapy and after docetaxel-containing chemotherapy were treated with transdermal estradiol (0.2 mg/24 h) for 4 weeks followed by the same dose of transdermal estradiol and paclitaxel poliglumex (PPX; 150 mg/m intravenous) every 28 days. The primary objective was to determine the level of activity of the regimen measured using a fraction of patients who experienced a confirmed decline in serum prostate-specific antigen (PSA) of 50% or more. A two-stage phase II study designed to identify a response rate of > or =25% required three responders among 21 patients in the first stage. Twenty-one patients who received a median of two earlier chemotherapy regimens were enrolled in the trial between March 2007 and May 2008. During the estradiol-only treatment phase, no patient had a PSA decline in excess of 50% and lesser PSA declines that ranged from 8.8 to 34.1% were seen in five patients. No patients achieved a > or =50% PSA decline following the addition of PPX and there were no responses in measurable disease. The median time to progression was 4 weeks. In conclusion, this regimen of low-dose transdermal estradiol induction followed by PPX does not have activity in taxane pretreated patients with castration-resistant prostate cancer.
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PMID:A phase II study of paclitaxel poliglumex in combination with transdermal estradiol for the treatment of metastatic castration-resistant prostate cancer after docetaxel chemotherapy. 2001 65