PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “PSA response”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed2005

Ixabepilone (epothilone B analogue BMS-247550) is active in chemotherapy-naive patients with hormone-refractory prostate cancer: a Southwest Oncology Group trial S0111.

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.

Adenocarcinoma↗
PubMed2004

High-dose calcitriol and carboplatin in metastatic androgen-independent prostate cancer.

Calcitriol acts synergistically with carboplatin in preclinical models of adenocarcinoma of the prostate. The authors sought to test high-dose oral calcitriol in combination with carboplatin in patients with metastatic androgen-independent prostate cancer. Seventeen patients received oral calcitriol (0.5 microg/kg) on day 1 and intravenous carboplatin (AUC 7 or AUC 6 in patients with prior radiation) on day 2, repeated every 4 weeks. PSA response was the primary end point and was defined as a 50% reduction confirmed 4 weeks later. Palliative response (2-point reduction or normalization of pain on the present pain intensity [PPI] scale without increased analgesic consumption) was also examined. One of 17 patients (6%, 95% CI, 0-28) achieved a confirmed PSA response. Four patients (24%, 95% CI, 7-49) had PSA reductions ranging from 24 to 38%. Of the 15 patients with a PPI > or = 1 point on entry, 3 (18%, 95% CI, 4-48) met criteria for palliative response. Treatment-related toxicity was mild and generally similar to that expected with single-agent carboplatin. Despite encouraging preclinical evidence, the addition of oral calcitriol to carboplatin in this study was not associated with an increase in the response rate when compared with the reported activity of carboplatin alone.

Adenocarcinoma↗
PubMed2005

A phase II study of nilutamide in men with prostate cancer after the failure of flutamide or bicalutamide therapy.

OBJECTIVE: To determine the prostate-specific antigen (PSA) response and time to PSA or radiographic progression in men with prostate cancer refractory to bicalutamide and/or flutamide therapy. PATIENTS AND METHODS: Men with histologically confirmed prostate cancer not amenable to curative surgery or radiation therapy were eligible for the study if they had radiographic or PSA progression on at least one antiandrogen (not nilutamide) despite continued androgen suppression and standard antiandrogen withdrawal periods. All men received nilutamide 150 mg/day orally for > or = 8 weeks unless there was unacceptable toxicity or disease progression. All men were evaluated for response, safety and toxicity. Baseline PSA levels, chest X-ray, bone scan and abdominopelvic computed tomography studies were obtained; the re-evaluation included PSA levels every 4 weeks and repeated imaging every 8 weeks in those with baseline abnormalities. The chest X-ray was repeated if there were pulmonary symptoms. Nineteen men were consented and 16 were evaluable for response. RESULTS: The median (range) Gleason score was 7 (6-9) and the median number of previous second-line therapies was 2 (1-4). Bicalutamide therapy had failed in all patients. At baseline, 13 (of 16 men) had radiographically evident disease, nine with diffuse osseous and four with radiographically measurable metastases. There was no grade 3/4 toxicity; the commonest grade 1/2 toxicities were constipation (three), sensory neuropathy (four), fatigue (six), and visual changes (two) involving transiently altered colour vision and sensitivity to light, respectively. Responses included three partial and 13 with progressive disease. CONCLUSIONS: The study was discontinued after a planned interim analysis because nilutamide had no apparent activity. Although well tolerated, nilutamide offers benefit to few men with prostate cancer in whom bicalutamide has failed.

Adult↗
PubMed2001

Phase II study of weekly docetaxel in symptomatic androgen-independent prostate cancer.

BACKGROUND: This study sought to define the activity and toxicity of weekly docetaxel in patients with androgen-independent prostate cancer and cancer-related pain. PATIENTS AND METHODS: Twenty-five patients were treated with docetaxel 36 mg/m2 i.v. administered weekly for six consecutive weeks followed by two weeks without treatment. This eight-week treatment cycle was repeated until progression or unacceptable toxicity. Endpoints included palliative response (a 2-point reduction on the 6-point Present Pain Intensity scale without an increase in analgesic consumption or a 50% decrease in analgesic use without an increase in pain), PSA response (a 50% decrease maintained at least four weeks), measurable disease response, survival, and toxicity. RESULTS: Twelve of 25 patients (48%, 95% confidence interval (95% CI): 28%-68%) had a palliative response. Eleven of the 24 patients who entered with an elevated PSA (46%, 95% CI: 25%-67%) had a PSA response. Two of five patients with measurable disease had a partial response. Toxicity of therapy was modest with no treatment-related mortality. Twenty-five percent of patients experienced a grade 3 or 4 hematologic toxicity and 36% of patients experienced a grade 3 non-hematologic toxicity. CONCLUSIONS: Weekly docetaxel is well tolerated in patients with androgen-independent prostate cancer and has significant activity as measured by relief of pain, reduction in PSA, and reduction in measurable disease.

Aged↗
PubMedDate not supplied

Phase II study of vinorelbine with low dose prednisone in the treatment of hormone-refractory metastatic prostate cancer.

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.

Adenocarcinoma↗
PubMed2005

Multicenter randomized phase II study of two schedules of docetaxel, estramustine, and prednisone versus mitoxantrone plus prednisone in patients with metastatic hormone-refractory prostate cancer.

PURPOSE: Mitoxantrone-corticosteroid is currently the standard palliative treatment in hormone-refractory prostate cancer (HRPC) patients. Recent clinical trials documented the high activity of the docetaxel-estramustine combination. We conducted a randomized phase II study to evaluate prostate-specific antigen (PSA) response (primary end point) and safety of two docetaxel-estramustine-prednisone (DEP) regimens and mitoxantrone-prednisone (MP). PATIENTS AND METHODS: One hundred thirty metastatic HRPC patients were randomly assigned to receive docetaxel (70 mg/m2 on day 2 or 35 mg/m2 on days 2 and 9 of each 21-day cycle) and estramustine (280 mg p.o. tid on days 1 through 5 and 8 through 12) or mitoxantrone 12 mg/m2 every 3 weeks; all patients received prednisone (10 mg daily). RESULTS: One hundred twenty-seven patients were assessable for PSA response and safety. A > or = 50% PSA decline was found in a greater percentage of patients in the docetaxel arms (67% and 63%) compared with MP (18%; P = .0001). Median time to PSA progression was five times longer with DEP than with MP (8.8 and 9.3 v 1.7 months, respectively; P = .000001). Overall survival was better in the docetaxel arms (18.6 and 18.4 months) compared with the MP arm (13.4 months), but not significantly so (P = .3). Crossover rates differed significantly among treatment arms (16%, 10%, and 48% in arms A, B, and C, respectively; P = .00001). Treatment-related toxicities were mild and mainly hematologic. CONCLUSION: The results of this randomized phase II study showed significantly higher PSA decline < or = 50% and longer times to progression in HRPC patients receiving DEP-based chemotherapy than MP, and that DEP could be proposed in this setting.

Adenocarcinoma↗
PubMed2002

[PSA-related parameters in prostate cancer relapsed after endocrine therapy].

PURPOSE: Prostate cancer is generally controlled by endocrine therapy even in an advanced state, but relapse may occur in many cases. Generally, the prognosis of a relapsed case is poor, but the prognosis differs case by case. We experienced 74 cases of prostate cancer relapsed after effective endocrine therapy, and investigated the relationship between the PSA-related parameters, clinical stage and prognosis. PATIENTS AND METHODS: We investigated 74 prostate cancer patients whose PSA declined 10 ng/ml or lower by the treatment consisting of endocrine therapy, but relapsed later. Pre-treatment PSA, the value of PSA nadir, the period from the start of treatment to PSA nadir, the period from the start of treatment to relapse, PSA doubling time (PSA-DT) at relapse and PSA response to the second line therapy at relapse were calculated, and compared with the clinical stage and prognosis. The relationship between each PSA parameter and clinical stage was tested using the Kruskal-Wallis test and chi 2 test. Cancer-specific survival after relapse in stage D patients was calculated by the Kaplan-Meier method and differences in prognosis were tested using the Logrank test. RESULTS: Pre-treatment PSA was significantly (p < 0.01) high, while the period from the start of treatment to relapse (p < 0.05) and PSA-DT at relapse (p < 0.01) was significantly short as the stage progressed. According to PSA response to the second line therapy at relapse, the rate of CR + PR was significantly (p < 0.05) high in clinical stage B + C group compared to clinical stage D group. The prognosis after relapse was significantly poorer in patients with relapse within 10 months after start of treatment than in those with relapse later, and in patients whose PSA-DT at relapse was shorter than 2 months than in those with a longer PSA-DT. CONCLUSIONS: The period from the start of treatment to relapse, and PSA-DT at relapse were useful PSA-related parameters for predicting prognosis after relapse, and for determining the strategy of cancer therapy after relapse. Using these data, the physician can inform the family and the patient of the prognosis more accurately, so that they can adjust future plans.

Aged↗
PubMed2001

Less pain does equal better quality of life following strontium-89 therapy for metastatic prostate cancer.

93 patients with hormone refractory metastatic prostate cancer were entered on a prospective study to measure reduction in pain and changes in quality of life (QoL) after the administration of 150 MegaBequerel (MBq) Strontium-89 (Sr-89). QoL was assessed using a validated instrument, the Functional Living Index - Cancer (FLIC) questionnaire. Pain response was measured using the Radiation Therapy Oncology Group scoring system. Overall there was limited QoL improvement over 3 months following Sr-89. However, in the 53 patients (63%) achieving pain responses, QoL did significantly improve within 6 weeks of receiving Sr-89 compared to patients with stable or worsening bone pain, and this was independent of other parameters that might influence QoL outcomes, such as performance status, baseline PSA and extent of skeletal disease (P = 0.004). PSA 'response' occurred in 30 patients (37%) over 4 months after Sr-89. This did not appear to correlate with clinical improvement. This study supports the presumption that improvement in pain following Sr-89 is accompanied by better QoL. The lack of correlation of PSA response and clinical parameters indicates that in the palliative setting, PSA may not provide a useful surrogate for treatment outcome.

Bone Neoplasms↗
PubMed1999

Endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer.

OBJECTIVE: To determine the endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of Zoladextrade mark (goserelin acetate, Zeneca Pharmaceuticals, Wilmington, Delaware, USA), a luteinizing hormone-releasing hormone agonist analogue, when administration was extended from every 12 weeks to every 13 weeks in patients with advanced prostate cancer. PATIENTS AND METHODS: Between July 1995 and May 1996, 59 patients with either locally advanced (T3 or T4) or metastatic prostate cancer were enrolled in an open-label, multicentre trial. Primary efficacy endpoints were testosterone measurements, and assessments of prostate specific antigen (PSA) response, subjective and objective response. Quality of life (QoL) was a secondary efficacy endpoint. RESULTS: Mean testosterone concentrations decreased to < 0.3 microgram/L by week 4 and remained so for the duration of treatment. There were no statistically significant differences in mean testosterone levels between weeks 12 and 13, or weeks 25 and 26. Serum testosterone suppression was adequate in all 58 evaluable patients at week 13, and 51 of 52 (98%) patients at week 26. Of the 58 evaluable patients, 52 (90%) had a PSA response. A subjective response was recorded for six of 11 evaluable patients. Of 58 patients evaluable for objective response, 46 (79%) had a partial response, three (5%) had stable disease and nine (16%) had objective progression. Except for a significant (P=0.014) decrease in overall sexual interest, QoL was unchanged during therapy. The most common side-effects, regardless of causality, were hot flushes (67%), pain (31%) and pelvic pain (22%). Mild injection-site complaints occurred with only three of 221 (1.4%) depot injections. CONCLUSIONS: Zoladextrade mark 10.8-mg depot, administered every 13 weeks to patients with advanced prostatic cancer, is well tolerated, provides adequate suppression of serum testosterone and produces PSA, subjective and objective responses.

Aged↗
PubMed1999

Effect of finasteride and/or terazosin on serum PSA: results of VA Cooperative Study #359.

BACKGROUND: Medical management of benign prostatic hyperplasia (BPH) giving rise to lower urinary tract symptomatology (LUTS) has emerged as the mainstay for first-line therapy. Prostate-specific antigen (PSA) is the most important method of detecting prostate carcinoma. The effect of finasteride on PSA has been widely reported. Little data exist with respect to alpha-adrenergic blocking therapy in men treated for BPH. In the present investigation we set out to evaluate the effect of these two forms of therapy. METHODS: Patients enrolled in the VA Cooperative Study #359 trial were evaluated. This study evaluated men with moderate LUTS owing to BPH in four treatment groups: placebo (P), finasteride (F), terazosin (T), and combination of finasteride plus terazosin (C). Men were recruited at 31 VA medical centers and had a baseline in 52-week PSA determination at the respective sites. RESULTS: There was no significant difference in baseline PSA between four groups (mean range, 2.0-2.9 ng/ml). Statistically significant reduction in PSA levels was observed at 52 weeks in the F and C arms (P < 0.001), whereas significant increases were observed in the T and P arms (P < 0.01). Additionally, there was no significant difference in PSA response between the T and P arms. Thirty percent of men in the C or F arms had more than 40-60% reduction of PSA. In contrast, the majority of men on T or P had less than 40% change in PSA. Only 35% of men on F or C had the expected 40-60% reduction in PSA level. CONCLUSIONS: These data demonstrate no clinically significant effect of T on PSA level. The heterogeneity of PSA response to F may make monitoring patients for the development of prostate cancer problematic.

Adrenergic alpha-Antagonists↗
PubMed2000

Palladium-103 brachytherapy for prostate carcinoma.

PURPOSE: A report of biochemical outcomes for patients treated with palladium-103 (Pd-103) brachytherapy over a fixed time interval. METHODS AND MATERIALS: Two hundred thirty patients with clinical stage T1-T2 prostate cancer were treated with Pd-103 brachytherapy and followed with prostate-specific antigen (PSA) determinations. Kaplan-Meier estimates of biochemical failure on the basis of two consecutive elevations of PSA were utilized. Multivariate risk groups were constructed. Aggregate PSA response by time interval was assessed. RESULTS: The overall biochemical control rate achieved at 9 years was 83.5%. Failures were local 3.0%; distant 6.1%; PSA progression only 4.3%. Significant risk factors contributing to failure were serum PSA greater than 10 ng/ml and Gleason sum of 7 or greater. Five-year biochemical control for those exhibiting neither risk factor was 94%; one risk factor, 82%; both risk factors, 65%. When all 1354 PSA determinations obtained for this cohort were considered, the patients with a proportion of PSAs < or = 0.5 ng/ml continued to increase until at least 48 months post-therapy. These data conformed to a median PSA half-life of 96.2 days. CONCLUSIONS: Prostate brachytherapy with Pd-103 achieves a high rate of biochemical and clinical control in patients with clinically organ-confined disease. PSA response following brachytherapy with low-dose-rate isotopes is protracted.

Aged↗
PubMed2002

Low serum testosterone level predicts worse response to endocrine therapy in Japanese patients with metastatic prostate cancer.

Patients with prostate cancer generally respond to androgen withdrawal therapy, but progression to androgen-independence is frequently observed later. To examine whether pretreatment serum androgen status could predict disease progression in metastatic prostate cancer, pretreatment serum testosterone, histological grade, extent of bony metastasis, serum prostate-specific antigen (PSA) response to hormone therapy, and prognosis of the 40 patients with untreated metastatic prostate cancer who received endocrine therapy were evaluated. Although there were no differences in age, pretreatment PSA level, extent of bony disease and histological grade between patients with normal testosterone and those with low testosterone, PSA response after endocrine therapy was better in normal testosterone group. There was a significantly longer interval to disease progression in patients with normal testosterone than in those with low testosterone. The patients with metastatic prostate cancer with low serum testosterone were in the high risk group of worse response to endocrine therapy. Additional therapy might be considered in those patients.

Aged↗
PubMed2006

Interleukin 6, a nuclear factor-kappaB target, predicts resistance to docetaxel in hormone-independent prostate cancer and nuclear factor-kappaB inhibition by PS-1145 enhances docetaxel antitumor activity.

PURPOSE: To investigate whether nuclear factor kappaB (NF-kappaB)/interleukin 6 (IL-6) was linked to docetaxel response in human prostate cancer cell lines, and whether inhibition of NF-kappaB sensitized tumor cells to docetaxel. We also aimed to correlate IL-6 (as a surrogate marker of NF-kappaB) and docetaxel response in hormone-independent prostate cancer (HIPC) patients. EXPERIMENTAL DESIGN: Hormone-dependent (LNCaP) and hormone-independent (PC-3 and DU-145) prostate cancer cell lines were exposed to docetaxel alone or combined with the NF-kappaB inhibitor PS-1145 (an inhibitor of IkappaB kinase-2). Effects of dose, exposure time, and schedule dependence were assessed. Activation of NF-kappaB was assayed by electrophoresis mobility shift assay and luciferase reporter assay, IL-6 levels by ELISA, and cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle and apoptosis were assessed by fluorescence-activated cell sorting analysis. Apoptosis was also measured by detection of cleavage of poly(ADP-ribose) polymerase. In patients with metastatic HIPC receiving docetaxel-based chemotherapy, IL-6 serum levels were assayed before chemotherapy and every 3 to 4 weeks thereafter. RESULTS: PC-3 and DU-145 cells had higher NF-kappaB activity, secreted more IL-6, and were more resistant to docetaxel than LNCaP cells. NF-kappaB activity was induced by docetaxel. Cotreatment with docetaxel and PS-1145 prevented docetaxel-induced NF-kappaB activation, reduced IL-6 production, and increased docetaxel effects on cell viability in PC-3 and DU-145 cells but not in LNCaP. Synergism with docetaxel and PS-1145, as assayed by median-effect principle, was observed in DU-145 and PC-3. In HIPC patients, pretreatment IL-6 serum levels correlated to prostate-specific antigen (PSA) response: median IL-6 level was 10.8+/-9.5 pg/mL in PSA responders versus 36.7+/-20.8 pg/mL (P=0.006) in nonresponders. A PSA response was also linked to a decline in IL-6 levels during treatment. Median overall survival was 6.8 months in patients with high IL-6 versus 16.6 months in those with low IL-6 (P=0.0007). On multivariate analysis, pretreatment IL-6 (P=0.05) was an independent prognostic factor for time to disease progression and survival. CONCLUSIONS: Inhibition of NF-kappaB emerges as an attractive strategy to enhance docetaxel response in prostate cancer. The interest of this view is further supported by a significant association between high IL-6 in sera of HIPC patients and decreased response to docetaxel.

Aged↗
PubMed2006

Vinorelbine, doxorubicin, and prednisone in androgen-independent prostate cancer.

BACKGROUND: Ultimately, patients with metastatic prostate cancer progress on androgen ablation therapy. The investigation of new chemotherapeutic regimens for the treatment of androgen-independent prostate cancer (AIPC) is essential. The authors conducted a Phase II trial with vinorelbine, doxorubicin, and daily prednisone (NAP) to investigate the antitumor activity and palliative response of this regimen in patients with AIPC. METHODS: Forty-six patients entered this Phase II combination chemotherapy trial. Patients were treated with both vinorelbine and doxorubicin at doses of 20 mg/m2 on Days 1, 8, and 15 every 28 days and prednisone 5 mg twice daily. Endpoints included prostate-specific antigen (PSA) response and palliation, as measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) instrument, the Brief Pain Inventory Scale, and a narcotic analgesic log. RESULTS: The median follow-up for all 46 patients was 13.4 months. Fifty-two percent of patients had impaired performance status at baseline. One responding patient remained on NAP and was progression-free at 11.5 months. Thirty-nine patients progressed, 3 patients died prior to response assessment, and 3 patients refused therapy. The median overall survival was 57 weeks (95% confidence interval [95% CI], 36-76 weeks), and the median time to disease progression was 17 weeks (range, 11-24 weeks). The PSA response among the 36 patients who completed 3 cycles of NAP was 42% (95% CI, 26-59%). There was a statistically significant improvement in quality of life measured both by the FACT-General instrument (P = .03) and the FACT-P instrument (P = .0006) over the 3 months compared with baseline measurements. Pain medicine use also improved: The median morphine equivalents among patients who were taking pain medications at the time of study enrollment showed a substantial decline after 1 cycle of treatment that was maintained. Pain (as assessed by the Brief Pain Inventory) improved compared with baseline pain at the 2nd-month assessment (worst pain, P = .08; least pain, P = .02; and average pain, P = .003). Overall, the regimen was tolerated well. The most common side effects were mild fatigue and gastrointestinal complaints (all of which were Grade 1 or 2 [according to Version 2.0 of the Expanded Common Toxicity Criteria]). Seventeen patients (37%) experienced Grade 3 or 4 neutropenia. Five patients (11%) developed a cardiac ejection fraction of <50% during treatment and had doxorubicin discontinued. No patients developed clinical congestive heart failure. CONCLUSIONS: The NAP combination produced substantive palliation and a moderate response rate in men with AIPC.

Aged↗
PubMed1997

PSA evolution: a prognostic factor during treatment of advanced prostatic carcinoma with total androgen blockade. Data from a Belgian multicentric study of 546 patients.

OBJECTIVES: To study the prognostic value of the prostate-specific antigen (PSA) response and its relationship with other initial prognostic factors during the treatment of advanced prostatic carcinoma with total androgen blockade. METHODS: Five hundred forty-six patients with advanced loco-regional (M0) or distant metastatic (M1) prostatic carcinoma treated with flutamide combined with either orchiectomy or LHRH analogues were included in this analysis. Initial patients characteristics and the PSA response were evaluated in relation to progression-free survival using a univariate and multivariate (Cox regression) analysis. RESULTS: The following prognostic factors were indicative of a decrease in progression-free survival: the absence of PSA normalization (< 4 ng/ml) after 3 or 6 months, M1 stage, high G grade, ECOG performance status > 1, presence of pain and absence of dysuria. In M1 patients the combination of PSA normalization after 3 or 6 months with initial G grade and ECOG performance status had the strongest predictive value. CONCLUSIONS: This study demonstrates that PSA normalization after 3 or 6 months along with initial tumor stage, grade and health status of the patient are the most important prognostic factors related to progression-free survival in the hormonal treatment of advanced prostatic carcinoma.

Aged↗
PubMed2004

Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer.

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. PATIENTS AND METHODS: Patients with metastatic prostate cancer, progressive after primary hormonal therapy, were randomised to receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day or hydrocortisone alone until disease progression. Centres could choose to add aminoglutethimide 1000 mg/day to hydrocortisone as second-line hormone therapy (HT) for all their patients. Randomisation was stratified by centre. Further chemotherapy was allowed after progression. The primary end point was progression-free survival (PFS). The final analysis was performed on a total of 414 patients. Reported results were all based on intention-to-treat analyses. All progressions and responses were reviewed by an independent panel. RESULTS: PFS was significantly prolonged in the VRL plus HT arm compared with the HT alone arm, according to the statistical hypothesis of the protocol (P=0.055 in the two-sided log-rank test with a pre-specified significance level of 10%). The 6-month PFS rates were 33.2% versus 22.8%, and the median durations of PFS were 3.7 versus 2.8 months. In the multivariate Cox analysis, which included age, Karnofsky performance status (PS), haemoglobin, alkaline phosphatase at study entry and number of prior hormonal treatments, the P value was decreased to 0.005. The prostate-specific antigen (PSA) response rate (> or =50% decline sustained for at least 6 weeks) was significantly higher for VRL plus HT compared with HT (30.1% versus 19.2%; P=0.01). Clinical benefit, defined as a decrease in pain intensity or analgesic consumption or an improvement of Karnofsky PS for at least 9 weeks, and at least stable assessment in the other two, was also more frequently observed in patients who received VRL plus HT versus HT alone (30.6% and 19.2%; P=0.008). There was no statistical difference in overall survival. Forty-three per cent of patients in the HT arm received at least one line of further chemotherapy after progression, compared with 28% of patients in the VRL-based arm. Aminoglutethimide did not seem to result in better efficacy for either arm. VRL plus HT was well tolerated, with a median administered relative dose intensity of 90%; grade 4 neutropenia occurred in 6.5% of patients and non-haematological toxicity was rare. CONCLUSIONS: The combination of VRL and hydrocortisone compared with hydrocortisone alone resulted in improved clinical benefit, PFS and PSA response rate. This therapeutic gain is similar to that previously reported with mitoxantrone in combination with low-dose corticosteroids. There was no gain in survival; however, the combination is well tolerated in this elderly group of patients, who often present cardiac co-morbidities, and therefore offers an active and safe therapeutic option for patients with hormone-refractory prostate cancer.

Aged↗
PubMed2006

A phase II trial of dexamethasone, vitamin D, and carboplatin in patients with hormone-refractory prostate cancer.

BACKGROUND: A Phase II prospective trial was performed to study the efficacy of combination therapy with dexamethasone, calcitriol (1,25-dihydroxyvitamin D3), and carboplatin in patients with hormone-refractory prostate cancer (HRPC). Preclinical data from prostate cancer cell lines suggested a synergistic effect of these therapies. METHODS: All patients had pathologically confirmed prostate cancer with at least 2 consecutive increases in prostate-specific antigen (PSA). Treatment started with 1 mg of oral dexamethasone given daily with 0.5 mcg of daily calcitriol added at the start of Week 5. Carboplatin (area under the concentration time curve = 2) was started at the beginning of Week 7. Initially, carboplatin was given weekly; however, the protocol was changed later to give carboplatin for the first 4 weeks of a 6-week cycle. Of 40 patients who consented to participate, 6 patients were ineligible or declined to start therapy, leaving 34 treated patients. The median follow-up was 80.7 weeks (range, 11.5-260 weeks). RESULTS: A formal PSA response was seen in 13 of 34 treated patients (38.2%; 95% confidence interval [95% CI], 22.2-56.4%). The median overall survival was 97.7 weeks (95% CI, 61-114 weeks). Significant adverse events that were observed during the trial period included 2 deaths (myocardial infarction and cardiogenic shock), 4 patients with Grade 3 neutropenia (according to the National Cancer Institute Common Toxicity Criteria, version 2.0), 2 patients with thrombosis, 2 patients with inflammatory bowel symptoms, and 2 patients with new-onset diabetes mellitus. CONCLUSIONS: The novel combination of dexamethasone, calcitriol, and carboplatin for patients with HRPC produced a PSA response in 13 of 34 patients and had an acceptable side-effect profile.

Aged↗