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)

Hormone-refractory prostate cancer is characterized by a low response rate following second-line therapy. Encouraging results have been reported in Phase II studies with estramustine associated with vinblastine or etoposide. Vinorelbine is a new semisynthetic vinca alkaloid that has demonstrated activity in prostate cancer. We therefore evaluated the activity of the following schedule: estramustine, 400 mg/m2 orally days 1-42; etoposide, 50 mg/m2 orally days 1-14; and 28-42; vinorelbine, 20 mg/m2 days 1, 8, 28, and 35; cycles being repeated every 8 weeks. Twenty-five patients have been included and are assessable for response and side effects. Patient characteristics were as follows: median age, 71 years (range 55-81); ECOG performance status 0-2; nonosseous disease, 3 cases; bone metastases, 23 cases. Sixty-two cycles have been delivered. Two patients with measurable disease and six patients with bone disease had a partial remission for an overall response rate of 32% (95% confidence interval 15-53%). Seven patients had stabilization of disease and 10 had progression of disease. Median duration of response was 3 months (range 2-5). Prostate-specific antigen in 14 patients (56%) decreased from baseline by at least 50%. Toxicity was manageable. Neutropenia was mild, with only three cases of grade III-IV toxicity. Two patients had severe anemia. The results of this study indicate that the schedule is active and well tolerated in hormone-refractory prostate cancer patients.
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PMID:Phase II study of estramustine, oral etoposide, and vinorelbine in hormone-refractory prostate cancer. 925 95

The purpose of this study was to evaluate the efficacy of vinorelbine treatment in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score for the subgroup of patients with pain), as well as its toxicity in patients with progressive metastatic androgen-independent prostatic carcinoma. 44 patients with prostatic carcinoma progressing after orchiectomy or during treatment with hormonal agents were treated with vinorelbine at a dose of 30 mg/m(2) intravenously (i.v.) on days 1 and 8 of a 21-day cycle. Inclusion criteria were metastatic progressive prostatic carcinoma with prostate-specific antigen (PSA) serum levels >/=3 x upper limit of normal, World Health Organization (WHO) performance status </=2, age <85 years and adequate bone marrow, liver and renal functions. Treatment was continued until progression or a maximum of 12 cycles. Treatment was delayed for a week if haematological toxicity grade >/=2 was observed on the day of scheduled vinorelbine administration. 9 patients received less than three cycles, 6 due to rapid tumour progression. Treatment at day 1 had to be delayed in 13.7% of 183 cycles. Treatment at day 8 had to be omitted in 19.7% of all cycles. Grade >/=3 granulocytopenia occurred in 18% of patients. 4 patients had severe constipation. In 7 patients (15.9%, Confidence Interval (CI) 6.6-30.1%), a PSA response (>/=50% reduction of PSA levels) was observed. Among 8 patients with measurable disease, 3 had partial remission and 1 no change. Median time to PSA progression in 43 assessable patients was 11.9 weeks (range 3-52 weeks). Median duration of PSA response was 14 weeks (9-30 weeks). Clinical benefit was seen in 7 of 31 cases (23%) with baseline pain, there was no association with PSA response. Vinorelbine is a fairly well tolerated drug with a moderate single agent activity in patients with androgen-refractory prostate cancer.
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PMID:Vinorelbine in androgen-independent metastatic prostatic carcinoma--a phase II study. 1214 53

Anti-tubulin couplets have activity in hormone-resistant prostate cancer. This study was designed to define the dose-limiting toxicity (DLT) and recommended phase II dose (RPTD) of the unique triplet combination of paclitaxel, estramustine phosphate (EMP) and vinorelbine (Pacl-E-Vin). Patients with advanced malignancies who had failed standard therapy, ECOG performance status (PS 0-2) and adequate organ function were included. Dose of EMP was fixed at 300 mg/m2/dose p.o. t.i.d. on days 1-3 and 8-10. Vinorelbine dose was 20 mg/m2/day i.v. on days 3 and 10. Paclitaxel was dose escalated from 40 to 50 mg/m /day i.v. on days 3 and 10. Cycles were repeated every 3 weeks. Twelve adults (median age 72) were entered on this study. Primary tumors included prostate (n=7), cervix (n=2), melanoma (n=1), colon (1) and lung with synchronous prostate cancer (n=1). Nine patients had received no prior chemotherapy, one had received a prior regimen and two had received two or more prior regimens. Of four evaluable patients at dose level 1, one patient had grade 3 neutropenia leading to the day 10 dose being withheld. Of five evaluable patients at dose level 2, there was one DLT (febrile neutropenia) and two grade 3 neutropenias leading to the day 10 dose being withheld. One patient had a lower extremity deep vein thrombosis. Other side effects were mild and reversible. Nine patients were evaluable for efficacy: three with prostate cancer had a greater than 50% prostate-specific antigen (PSA) response, and a patient with synchronous prostate and lung cancer had a greater than 50% PSA response. We conclude that the DLT of Pacl-E-Vin is neutropenia. RPTD is vinorelbine 20 mg/m2, paclitaxel 40 mg/m2, both administered on days 3 and 10, and EMP 900 mg/m2/day on days 1-3 and 8-10, q3w. Dose omission at day 10 followed by 20% dose reduction of paclitaxel and vinorelbine is recommended in the event of grade 3 neutropenia. Activity in hormone-refractory prostate cancer is promising and warrants phase II evaluation.
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PMID:A phase I study of paclitaxel, estramustine phosphate and vinorelbine (Pacl-E-Vin) in advanced malignancies: triple tubulin targeting. 1254 60

A phase II trial of vinorelbine and low dose prednisone in hormone-refractory metastatic prostate cancer was conducted in order to investigate its safety, efficacy and impact on quality of life. Vinorelbine was administered at the dose of 25 mg/m(2) i.v. weekly for 12 weeks and then biweekly, along with 10 mg of daily oral prednisone until time of progression. Fourteen patients, median age of 74 years, were treated. The treatment was generally well tolerated with leukopenia and anemia as the major side effects. One patient achieved partial remission and eleven remained with stable disease. One of the eleven patients with stable disease had a dramatic PSA response from 1000 to 236 ng/ml; seven of these progressed after week twelve when vinorelbine was given biweekly. PSA response occurred in 5 of 14 patients. The median time to progression was 28 weeks and the median survival was 17 months. Nine out of the 14 accrued patients were evaluable for quality of life assessment. Five of them improved, three remained unchanged and two had a slight worsening. Four patients had improvement in pain control and fatigue. Our preliminary data suggest that the combination of vinorelbine/prednisone has modest activity in metastatic prostate cancer with a very favorable toxicity profile and is very well tolerated in this group of elderly patients.
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PMID:Phase II study of vinorelbine with low dose prednisone in the treatment of hormone-refractory metastatic prostate cancer. 1279 40

Anticancer drugs docetaxel and vinorelbine suppress cell growth by altering microtubule assembly and activating the proapoptotic signal pathway. Vinorelbine and docetaxel have been approved for treating several advanced cancers. However, their efficacy in the management of advanced hormone-refractory prostate cancer remains to be clarified. Microtubule damage by some anticancer drugs can activate the ERK survival pathway, which conversely compromises chemotherapeutic efficacy. We analyzed the effect of ERK inhibitors PD98059 and U0126 on vinorelbine- and docetaxel-induced cell growth suppression of androgen-independent prostate cancer cells. In androgen-independent C-81 LNCaP cells, inhibition of ERK by PD98059, but not U0126, plus docetaxel resulted in enhanced growth suppression by an additional 20% compared to the sum of each agent alone (p < 0.02). The combination treatment of docetaxel plus PD98059 also increased cellular apoptosis, which was in part due to the inactivation of Bcl-2 by increasing phosphorylated Bcl-2 by more than 6-fold and Bax expression by 3-fold over each agent alone. At these dosages, docetaxel alone caused only marginal phosphorylation of Bcl-2 (10%). Docetaxel plus U0126 had only 20% added effect on Bcl-2 phosphorylation compared to docetaxel alone. Nevertheless, both U0126 and PD98059 exhibited an enhanced effect on docetaxel-induced growth suppression in PC-3 cells. No enhanced effect was observed for vinorelbine plus PD98059 or U0126. Thus, the combination therapy of docetaxel plus PD98059 may represent a new anticancer strategy, requiring lower drug dosages compared to docetaxel monotherapy. This may lower the cytotoxicity and enhance tumor suppression in vivo. This finding of a combination effect could be of potential clinical importance in treating hormone-refractory prostate cancer.
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PMID:ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells. 1450 50

To study the mechanisms of the development of hormone refractory prostate cancer, we established an androgen-independent (AI) prostate cancer cell line derived from hormone-dependent (AD) LNCaP cells. Our previous studies have demonstrated that AI cells are deficient in expression of p21(WAFl/CIP1) (p21) due to overexpressed AR and are resistant to apoptosis. In this study, the induction of p53 and p21 expression by vinorelbine (Navelbine) was compared between AD and AI cells in an attempt to understand the difference(s) in apoptotic signalling pathways in these cells. Using a series of deletion of p21 reporter constructs, we found that vinorelbine mediated p21 induction in a p53-dependent manner in AD cells. In contrast, p21 expression restored by vinorelbine in AI cells was found to be through both p53-dependent and-independent pathways. In the absence of two p53 binding sites, Spl-3 and Spl-4 sites, in the promoter of human p21 gene, were found to be required for vinorelbine-mediated p21 activation. No p21 induction was observed by paclitaxel in AI cells. Exposure of AI cells to paciltaxel followed by vinorelbine produced synergism. Our data, thus, provide a basis for the synergistic combination of vinorelbine and paclitaxel for the treatment of advanced prostate cancer.
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PMID:Unique induction of p21(WAF1/CIP1)expression by vinorelbine in androgen-independent prostate cancer cells. 1456 33

Vegetables and fruit help the prevention and the therapy of several kinds of cancer because they contain micronutrients, a class of substances that have been shown to exhibit chemopreventive and chemotherapeutic activities. In the present study the effects of resveratrol (100 and 200 microM), a phytoalexin found in grapes, and of the ethanolic extract of propolis (50 and 100 microg/ml), a natural honeybee hive product, were tested in androgen-resistant prostate cancer cells (DU145), a cell line resembling the last stage of prostate carcinoma. A comparison between the activity of these micronutrients and vinorelbine bitartrate (Navelbine), a semi-synthetic drug normally used in the therapy of prostate cancer, was conducted. Several biochemical parameters were tested, such as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase release), cell redox status (nitric oxide formation, reactive oxygen species production, reduced glutathione levels), genomic DNA fragmentation (COMET assay) with special attention on the presence of apoptotic DNA damage (TUNEL test), and possible mitochondrial transmembrane potential alteration (deltapsi). Our results point out the anticancer activity of resveratrol and propolis extract in human prostate cancer, exerting their cytotoxicity through two different types of cell death: necrosis and apoptosis, respectively. The data obtained suggest the possible use of these micronutrients both in alternative to classic chemotherapy, and in combination with very low dosage of vinorelbine (5 microM).
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PMID:Resveratrol and propolis as necrosis or apoptosis inducers in human prostate carcinoma cells. 1549 Sep 73

In the Western world cancer is the second leading cause of mortality, and prostate carcinoma represents in men the second most important type of cancer-causing death. We have already shown that resveratrol (200 microM) triggers in DU145, an androgen-resistant prostate cancer cell line, a necrotic-like cell death, while propolis ethanolic extract (100 microg/ml) causes an apoptotic-like cell demise. The present research is aimed to better elucidate the molecular mechanisms activated by the two micronutrients. Vinorelbine bitartrate, a drug widely used in prostate cancer therapy, was utilized as a reference drug, because it is known to induce apoptosis. The combined treatments between the micronutrients and vinorelbine have been studied to test a possible vinorelbine dose reduction, avoiding its side effects without altering its cytotoxic action. In this investigation SEM and TEM analyses were performed to examine the morphological modifications induced; our observations confirmed necrotic cell features after treatment with resveratrol, and apoptotic modifications after propolis. We also measured cell cycle progression to study a correlation with p21 and p53, two well-known cell cycle checkpoints. The levels of HSP27 and HSP70, two chaperones also exerting antioxidant/antiapoptotic functions, were been also analyzed. Our data indicate that the two micronutrients modulate cell cycle distribution, increasing p53 levels, without the induced HSPs being able to rescue DU145 from death. The results presented suggest chemotherapy based on resveratrol and propolis, alone or in combination with vinorelbine, as a potential useful tool for prostate cancer therapy; the increase in cell cycle control and the modulation of HSPs expression reinforce this suggestion.
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PMID:Resveratrol and propolis extract: an insight into the morphological and molecular changes induced in DU145 cells. 1655 47