Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amonafide (benzisoquinolinedione; NSC 308847) was subjected to a Phase II trial for the treatment of advanced hormone-refractory carcinoma of the prostate. In addition to adequate baseline organ functions, patients were required to have a favorable performance status, bidimensionally measurable disease and no prior chemotherapy. Amonafide was given at a dose of 225 mg/m2 intravenously daily for 5 days. Treatment cycles were repeated every 21 days. Dose escalation and reduction schema were used based upon toxicities from preceding cycles. Of 47 patients enrolled, 43 were evaluable. The most common toxicities were hematologic to include leukopenia (72%), granulocytopenia (32.6%), and thrombocytopenia (44.2%). There were no complete responses and only 5 partial responses for an overall response rate of 12% (95% confidence interval: 4-25%). The results indicate that Amonafide, in the dose and schedule tested, lacks sufficient activity against hormone-refractory prostate cancer to warrant further trials.
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PMID:Phase II trial of amonafide for the treatment of advanced, hormonally refractory carcinoma of the prostate. A Southwest Oncology Group study. 797 72

Rhenium-186 (tin) hydroxyethylidene diphosphonate (186Re-HEDP), a bone-seeking radiopharmaceutical, has been successfully used in the treatment of patients with painful bone metastases. Toxicity is usually limited to reversible thrombocytopenia. An infrequent but clinically significant side effect is the occurrence of transient cranial neuropathy. We report on two prostatic cancer patients with metastatic bone cancer. Both patients developed transient cranial neuropathy shortly after treatment with 186Re-HEDP. Transient neuropathy of cranial nerves needs to be distinguished from neurological abnormalities caused by disease progression.
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PMID:Transient cranial neuropathy in prostatic cancer with bone metastases after rhenium-186-HEDP treatment. 877 46

Hormone refractory prostate carcinoma is an incurable disease. Therapy affecting the tissue matrix at the level of the cytoskeleton has been demonstrated to inhibit prostate cancer growth. In vivo and in vitro evidence demonstrated vinblastine and tamoxifen to be agents that would interact to inhibit prostate cancer growth by microtubule inhibition. This study evaluated the effectiveness of these agents in combination in 22 patients with metastatic hormone refractory prostate cancer. Patients received tamoxifen 20 mg twice daily continuously plus vinblastine 4 mg/m2 on days 1, 8, 15, 22, 28, and 35 every 49 days. Disease response was assessed after the first two cycles of therapy. No partial or complete responses were definitively identified. Only 23% of participants received two or more full cycles of therapy. Major toxicities included grade 1-3 leukopenia (73%), grade 2-3 anemia (64%), and two participants experienced a grade 3/4 thrombocytopenia. Only two participants experienced a greater than 50% decrease in serum PSA, one of which may have been attributed to a flutamide withdrawal syndrome. We conclude that the dosage and schedule of vinblastine and tamoxifen used in this study is inactive in the treatment of metastatic hormone refractory prostate cancer.
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PMID:A phase II evaluation of oral tamoxifen and intermittent intravenous vinblastine in hormone-refractory adenocarcinoma of the prostate. 882 79

We report three cases of transient acute renal failure accompanied by thrombocytopenia all occurring within 48 h of percutaneous transperineal cryoprostatectomy. Renal function spontaneously improved in all three patients, who currently have normal renal function and are voiding without difficulty. No known risk factor or specific etiology for the renal failure could be identified; therefore, we conclude that the renal failure is most likely secondary to the cryosurgery procedure, a common link shared by all three patients. We are currently administering intravenous mannitol before initiation of the freeze and have seen no further episodes of postcryosurgical acute renal failure in > 50 patients with prostate cancer. Because cryosurgery is currently becoming a more pervasive treatment option for localized prostate cancer, we believe it most important to report this heretofore unrecognized potential complication.
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PMID:Acute renal failure with thrombocytopenia after cryosurgery of the prostate. 908 45

Recent advances in radionuclide therapy offer a new approach for the management of metastatic bone pain. This paper reports the results of dosage escalation studies with 186Re-HEDP as a bone-seeking radiopharmaceutical in patients with bone metastases originating from breast or prostate cancer with regard to toxicity, pharmacokinetics and bone marrow dosimetry and the palliating effect on bone pain. Thrombocytopenia proved to be the dose limiting factor and 186Re-HEDP showed a considerable efficacy in end-stage patients with metastatic bone pain.
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PMID:Treatment of metastatic bone pain using the bone seeking radiopharmaceutical Re-186-HEDP. 917 33

To assess the tumor targeting, safety, and efficacy of monoclonal antibody 131I-labeled CC49 in patients with androgen-independent prostate cancer, 16 patients received 75 mCi/m2 of the radiolabeled antibody after 7 days of IFN-gamma pretreatment. Sequential tumor biopsies in three patients showed a median 5-fold (range, 2-6-fold) increase in the proportion of cells staining positively for the TAG-72 antigen, whereas one showed a decrease in staining. Fourteen patients received 131I-labeled CC49, whereas 2 showed a disease-related decrease in performance status, precluding antibody treatment. The antibody localized to sites of metastatic androgen-independent prostate cancer in 86% (12 of 14; 95% confidence interval, 57-95%) of cases. Both osseous and extraosseous sites were visualized, and in six (42%) patients, more areas were visible when the radioimmunoconjugate was used than were apparent when conventional scanning techniques were used. The localization of the conjugate in the marrow cavity was usually a site not visualized by the radionuclide bone scan, in which the isotope localizes primarily to the tumor-bone interface. The dose-limiting toxicity was thrombocytopenia because five (36%) patients showed grade IV and seven (50%) showed grade III effects. In addition, six (42%) patients, four of whom were hospitalized, showed a flare in baseline pain, and four showed a decrease in pain. No patient showed a >50% decline in prostate-specific antigen, although radionuclide bone scans remained stable in four cases for a median of 4 months. The results are consistent with dosimetry estimates showing that the delivered dose to tumor was subtherapeutic and suggest that approaches that exclusively target the bone tumor interface or the marrow stroma may be unable to completely eradicate disease in the marrow cavity. For CC49, improving outcomes would require repetitive dosing, which was precluded by the rapid development of a human antimouse antibody response.
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PMID:Interferon-gamma and monoclonal antibody 131I-labeled CC49: outcomes in patients with androgen-independent prostate cancer. 953 32

3 weeks after commencing treatment with estramustine phosphate, typical manifestations of hemolytic-uremic syndrome occurred in a 66-year-old patient with prostate cancer. Urinary tract obstructions were excluded and no renal damage could be identified. An improvement in renal function was achieved by stopping estramustine phosphate and infusing adequate amounts of fluids and electrolytes. Anemia and thrombocytopenia also progressively improved after the discontinuation of chemotherapy. Nausea and vomiting, hepatotoxicity, impotence, reduced libido and hypercalcemia are major side effects of estramustine phosphate, and would be difficult to explain our observations without considering the role played by estramustine phosphate. Our observations suggest that estramustine phosphate might play either a direct role or produce a side effect within the context of latent paraneoplastic syndrome. The improvement in renal function which occurred when treatment stopped might confirm our hypothesis.
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PMID:Hemolytic-uremic syndrome during therapy with estramustine phosphate for advanced prostatic cancer. 994 96

For patients with local recurrence of prostate cancer after definitive irradiation therapy there is no treatment widely considered safe and effective. After extensive preclinical testing of prodrug gene therapy in vitro and in vivo, we conducted a phase I dose escalation clinical trial of intraprostatic injection of a replication-deficient adenovirus (ADV) containing the herpes simplex virus thymidine kinase gene (HSV-tk) injected directly into the prostate, followed by intravenous administration of the prodrug ganciclovir (GCV). Our goal was to determine safe dose levels of the vector for future trials of efficacy. Patients with a rising serum prostate-specific antigen (PSA) level and biopsy confirmation of local recurrence of prostate cancer without evidence of metastases one or more years after definitive irradiation therapy were eligible for the trial. After giving informed consent, patients received injections of increasing concentrations of ADV/HSA-tk in 1 ml into the prostate under ultrasound guidance. Ganciclovir was then given intravenously for 14 days (5 mg/kg every 12 hr). Patients were monitored closely for evidence of toxicity and for response to therapy. Eighteen patients were treated at 4 escalating doses: group 1 (n = 4) received 1 x 10(8) infectious units (IU); group 2 (n = 5) received 1 x 10(9) IU; group 3 (n = 4) received 1 x 10(10) IU; group 4 (n = 5) received 1 x 10(11) IU. Vector was detected by PCR of urine samples after treatment, increasing in frequency and duration (up to 32 days) as the dose increased. All cultures of blood and urine specimens were negative for growth of adenovirus. Minimal toxicity (grade 1-2) was encountered in four patients. One patient at the highest dose level developed spontaneously reversible grade 4 thrombocytopenia and grade 3 hepatotoxicity. Three patients achieved an objective response, one each at the three highest dose levels, documented by a fall in serum PSA levels by 50% or more, sustained for 6 weeks to 1 year. This study is the first to demonstrate the safety of ADV/HSV-tk plus GCV gene therapy in human prostate cancer and the first to demonstrate anticancer activity of gene therapy in patients with prostate cancer. Further trials are underway to identify the optimal distribution of vector within the prostate and to explore the safety of repeat courses of gene therapy.
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PMID:In situ gene therapy for adenocarcinoma of the prostate: a phase I clinical trial. 1034 May 55

Anthracyclines and cisplatin have been shown separately to have modest activity in prostate cancer. The synergism between anthracyclines and cisplatin, with the lack of overlapping toxicities, led to the conduct of this phase II trial of the combination of epirubicin and cisplatin in hormone-refractory metastatic prostate cancer. Twenty-one evaluable patients with hormone-refractory metastatic prostate cancer received epirubicin 100 mg/m2 followed by cisplatin 80 mg/m2 with prehydration and mannitol diuresis. Epirubicin and cisplatin produced a biochemical response (>50% decrease in tumor marker) in 32% of patients, symptomatic improvement in 38%, and a response in measurable and evaluable disease sites in 14%. Toxicities were mainly hematologic, with 77% and 41% >grade 2 neutropenia and thrombocytopenia, respectively. Greater than grade 2 toxicities were: cardiac (three), renal secondary to sepsis (one), nausea and vomiting (two), weakness (one), mucositis (one), and diarrhea (one). The combination of epirubicin and cisplatin was associated with manageable toxicities in this elderly population; however, antitumor activity was marginal in this disease. Participation in clinical trials should continue to be offered to patients with hormone-refractory metastatic prostate cancer.
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PMID:Combination of epirubicin and cisplatin in hormone-refractory metastatic prostate cancer. 1052 Oct 61

The toxicity of 186Re-1,1-hydroxyethylidene diphosphonate (186Re-HEDP) therapy in patients with painful bone metastases is mainly limited to thrombocytopaenia. The aim of this study was to investigate the influence of bone marrow scintigraphy on the prediction of decreased platelet counts after 186Re-HEDP therapy. Twenty-nine prostatic cancer patients with multiple painful bone metastases were included in the study. From a pre-therapy nanocolloid bone marrow scintigram, the bone marrow index (BMI) was determined as an indicator of the extent of bone marrow involvement. The influence of the BMI on the prediction of percent decrease in platelet counts was investigated. The mean BMI was 59 +/- 20. Regression analysis showed that the BMI does not improve the relationship between percent reduction in platelet count and administered dose. In contrast, we previously showed that the bone scan index (BSI) does predict the percent reduction in platelet counts before treatment. We conclude that bone marrow scintigraphy does not provide any additional information on platelet toxicity after a therapeutic dose of 186Re-HEDP. Bone scintigraphy is preferred in the prediction of reduced platelet counts.
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PMID:Can bone marrow scintigraphy predict platelet toxicity after treatment with 186Re-HEDP? 1053 89


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