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Results for “PSA response”

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PubMed2003

Biweekly administration of low-dose docetaxel in hormone-resistant prostate cancer: pilot study of an effective subtoxic therapy.

Taxane-based chemotherapy has shown activity but also toxicity when administered at standard doses in patients with hormone-resistant prostate cancer (HRPC). In this pilot study, we investigated biweekly low-dose docetaxel in patients with HRPC as a convenient regimen with low toxicity. Sixteen patients with metastatic HRPC entered the study. Median age was 73 years, median performance status (PS) was 2, and median Gleason score was 9. All patients had undergone and failed combined androgen-blockade therapy (luteinizing hormone-releasing hormone analogue plus antiandrogen) for their metastatic disease; 3 had also been treated with mitoxantrone. Treatment consisted of docetaxel 30 mg/m2 administered every 2 weeks. Prostate-specific antigen (PSA) response, characterized by a 50% decrease of PSA level confirmed 4 weeks later, was the primary endpoint. Durations of PSA response and toxicity assessment were secondary endpoints. A total of 136 biweekly docetaxel doses were administered, with a median of 8.5 doses per patient (range, 2-24). Six patients (38%; 95% confidence interval, 25%-43%) fulfilled the criteria of PSA response. Median duration of PSA response was 4.5 months (range, 3-12). Toxicity was negligible: myelotoxicity was practically absent, whereas 3 patients developed grade 1 alopecia and 1 patient developed dacryorrhea. We conclude that our study provides evidence that biweekly docetaxel at 30 mg/m2 can be considered an effective nontoxic therapeutic option for patients with HRPC. Confirmation of these preliminary data in larger-scale trials is justified

Aged↗

PubMed2000

Prostate specific antigen response to mitoxantrone and prednisone in patients with refractory prostate cancer: prognostic factors and generalizability of a multicenter trial to clinical practice.

PURPOSE: We determine prostate specific antigen (PSA) response and durability, and prognostic factors associated with response and survival in patients with symptomatic hormone refractory prostate cancer treated with mitoxantrone and prednisone at a single institution. We then compare the results with those of a randomized phase III clinical trial. MATERIALS AND METHODS: A retrospective review of all 133 patients treated with mitoxantrone and prednisone at Princess Margaret Hospital since 1994 was performed. PSA response and duration, and overall survival were determined as well as the influence of baseline factors on these outcome parameters. Results were compared to those for patients randomized to receive mitoxantrone and prednisone in the Canadian clinical trial which demonstrated palliative benefit of this regimen. RESULTS: Patients treated after trial closure had shorter survival (p = 0.003) but represented a poorer prognosis cohort. PSA response of the trial and post-trial cases was 34% and 28%, respectively (p = 0.36), and median duration of response was 118 and 175 days or greater, respectively. Factors predictive of PSA response in the non-trial cohort were longer time from diagnosis of prostate cancer (p = 0. 027) and higher baseline PSA (p = 0.013). Factors predictive of increased survival in both groups were younger age (p <0.04), better baseline Eastern Cooperative Oncology Group performance status (p <0. 02), and higher hemoglobin (p </=0.05) and PSA response (p <0.0001). Gleason score was not predictive of response or survival. CONCLUSIONS: Although patients treated outside of the trial had poorer prognostic features, rates of PSA response to mitoxantrone and prednisone were comparable. Factors predictive of survival were similar in the 2 cohorts. Results of the randomized trial are generalizable to clinical practice.

Adenocarcinoma↗

PubMed2005

Prostate-specific antigen response duration and risk of death for patients with hormone-refractory metastatic prostate cancer.

OBJECTIVES: To evaluate whether the time to return to the baseline prostate-specific antigen (PSA) level (PSA response duration) is significantly associated with the time to death after randomization for men with hormone-refractory metastatic prostate cancer. METHODS: The study (n = 213) and validation (n = 281) cohorts constituted 494 men with hormone-refractory metastatic prostate cancer treated in four prospective randomized Phase II studies between February 1996 and October 2001. Cox regression analysis was used to evaluate whether a significant association existed between the PSA response duration and the time to death after randomization, controlling for treatment and known prognostic factors. RESULTS: A decreasing PSA response duration was significantly associated with a shorter survival after randomization in the study (P = 0.001) and validation (P = 0.02) cohorts, controlling for treatment and known prognostic factors, which included serum PSA, lactate dehydrogenase, alkaline phosphatase, and hemoglobin levels and the Eastern Cooperative Oncology Group performance status. The adjusted hazard ratio for death was 1.9 (95% confidence interval 1.4 to 2.6; P = 0.0002) and 2.1 (95% CI 1.2 to 3.5; P = 0.01) for men in the study and validation cohorts, respectively, whose PSA response duration was shorter than the median value of 3 months. The PSA response duration dichotomized about the median remained significantly associated with death whether patients in the validation cohort experienced at least a 50% reduction (P = 0.05) in the PSA level or not (P = 0.03). CONCLUSIONS: The duration of the PSA response to treatment is significantly associated with length of survival for men with hormone-refractory metastatic prostate cancer.

Adult↗

PubMed1997

Intermittent androgen deprivation after PSA-complete response as a strategy to reduce induction of hormone-resistant prostate cancer.

OBJECTIVES: The increasing interest in exploring the use of intermittent androgen deprivation in prostate cancer has prompted a retrospective review of patients who elected to stop treatment. METHODS: Case records were reviewed. RESULTS: Twenty patients after 3 to 48 months (median 12) of endocrine therapy elected to stop therapy. Thirteen subsequently relapsed after a median observation of 9 months. Seven of 20 patients continue progression-free for 9 to 42 months (median 33). After second-line therapy, 75% of patients with a relapse remain progression-free at 2 years. Progression-free survival was higher in patients at Stage M0 (82% at 1 year) versus M+ (29% at 1 year). CONCLUSIONS: With 10 of 13 patients demonstrating an ongoing second PSA response, 45% of patients showing no progression, and 85% alive at 3 years, these results support findings from previous publications that suggest that there are no major risks with use of intermittent hormone therapy. However, in the future, there is an urgent need that such studies should be randomized and done in the context of audit-based research and development programs. The resources released could then be invested with respect to further improvements in treatment of prostate cancer, possibly considering such a combined approach with immunotherapy as an alternative to surgery or radiotherapy for early disease in elderly patients with long PSA-doubling time.

Aged↗

PubMed2005

Clinical outcome of oral uracil/tegafur (UFT) therapy for patients with hormone refractory prostate cancer.

There is no standard therapeutic strategy for advanced hormone refractory prostate cancer after the initial hormonal therapy fails. The objective of this study was to retrospectively evaluate the clinical outcome of the oral anticancer agent, uracil/tegafur (UFT) for patients with hormone refractory prostate cancer. This study included 68 patients with hormone refractory prostate cancer treated by oral administration of UFT (300-600 mg/day). All patients had previously received maximum androgen blockade (MAB) which failed. In this series, response was defined as more than 50% decrease from the baseline prostate specific antigen (PSA) value at the start of second line therapy. Upon initiating administration of UFT, a reduction in PSA value was observed in 41 of the 68 patients (60.3%), among whom 13 (19.1%) were regarded as responders; however, PSA value continued to increase in the remaining 27 (39.7%). Median duration of PSA response was 7 months (range 1-22 months). During the observation period, there were no severe side effects due to UFT administration, but 7 patients transiently presented appetite loss. Patients without bone metastasis at the initial diagnosis or whose serum PSA value at the start of UFT therapy was less than 2.0 ng/ml showed a significantly higher incidence of PSA response to UFT; however, other factors examined had no significant impact on PSA response to UFT. Furthermore, cause-specific survival in responders to UFT therapy was significantly better than that in non-responders. These findings suggest that administration of UFT after the failure of initial MAB therapy can achieve a comparatively favorable PSA response without severe side effects; therefore, it may be worthy to consider administering UFT to patients with hormone refractory prostate cancer.

Administration, Oral↗

PubMed2002

EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.

Many chemotherapeutic regimens combined with estramustine phosphate (EMP) have been elaborated for the treatment of hormone-refractory prostate cancer over 30 years. However, older EMP-based combination chemotherapies with vinblastine, vinorelbine, doxorubicin or cyclophosphamide showed relatively low PSA response rate (25-58%) accompanied with high toxicities. On the other hand, newly developed EMP-based combination regimens with etoposide, pacitaxel, carboplatin or docetaxel demonstrated promising PSA response rate (43-77%) with moderate to severe toxicity in the rate of thromboembolic event (5-18%) and of neutropenia (9-41%). Treatment-related death was less in the latter combination group (5/615, 0.8%) than that in the former group (3/234, 1.3%). Of note, in the docetaxel combination with EMP, PSA response rate is as high as 77% with high rate (41%) of neutropenia but no treatment-related death was observed. Docetaxel combination with EMP seems to be the best regimen, though not completely justified by randomized trials, to be selected in the modern era, which will be followed by paclitaxel, carboplatin and EMP combination with PSA response rate of 71%. In addition, an interim report in 83 patients was presented. They were not consecutively enrolled but were treated on low-dose EMP monotherapy for previously untreated advanced prostate cancer in Department of Urology of Tokyo University and our 21 affiliated hospitals. Overall PSA response rate was as high as 93.4% out of 76 assessable patients. However, overall toxicity rate was abnormally high (39.5%) with drug discontinuation rate of 32.1%. The reason of low drug compliance may be attributed to gastrointestinal symptoms. To overcome the low drug compliance, appropriate patients for EMP administration should be selected by using gene analysis on the basis of sophisticated tailor-made medicine.

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PubMed2002

Vinorelbine in androgen-independent metastatic prostatic carcinoma--a phase II study.

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.

Aged↗

PubMed2001

Nilutamide: possible utility as a second-line hormonal agent.

OBJECTIVES: To study the ability of nilutamide to induce prostate-specific antigen (PSA) responses in patients with hormone-resistant prostate cancer who had been exposed to prior antiandrogen therapy, because resistance to antiandrogens may be mediated by altered binding to a mutated or overexpressed androgen receptor and because an alternative antiandrogen may overcome such resistance. Nilutamide is a little used antiandrogen that has a chemical structure distinct from that of the other two antiandrogens, flutamide and bicalutamide. METHODS: Fourteen patients with hormone-resistant prostate cancer were treated with nilutamide 150 mg/day (n = 12) or 300 mg/day (n = 2). Seven had been treated with one prior antiandrogen (all with bicalutamide), five with both bicalutamide and flutamide, and two had received bicalutamide and prior chemotherapy. RESULTS: In a retrospective analysis, 7 (50%) of the 14 patients had a greater than 50% decline in their PSA level, and 4 of the 6 patients with bone pain experienced subjective improvement. The median duration of the PSA response was 11 months (range 2 to 28+) with 2 of the 7 patients still experiencing a PSA response. In addition, 3 patients (20%) had brief and minor PSA responses (less than 50%). CONCLUSIONS: A subset of patients, whose disease progresses with prior antiandrogen therapy, may experience a PSA response to nilutamide. The role of nilutamide in such hormone-resistant patients deserves additional prospective study.

Androgen Antagonists↗

PubMed2003

3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot) in advanced prostate cancer: results from an Italian, open, multicenter trial.

OBJECTIVES: To determine the endocrine effects, efficacy and tolerability of the 3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot; 'Zoladex' is a trade mark of the AstraZeneca group of companies) in the treatment of patients with advanced prostate cancer. METHODS: Between February 1996 and October 1997, this open, multicentre study enrolled 120 patients with locally advanced (T3/4) or metastatic (N+ or M1) disease, or an increase in prostate-specific antigen (PSA) level after radical prostatectomy. Patients received goserelin acetate 10.8-mg depot every 12 weeks until clinical progression or interruption for adverse events or other reasons. RESULTS: The mean testosterone concentrations were suppressed to the castration range (< or =2 nmol/l) after 4 weeks of treatment and remained suppressed throughout the study. In total, 99/115 (86%) patients had a serum PSA response, and the mean PSA value decreased significantly during treatment (p = 0.006). The mean PSA level at baseline was significantly lower in patients without disease progression compared to those who experienced disease progression (p = 0.0002). Goserelin acetate 10.8-mg depot was well tolerated and there were no injection site reactions. CONCLUSIONS: The goserelin acetate 10.8-mg depot is well tolerated with no injection site reactions. It produces PSA responses and provides reliable suppression of serum testosterone.

Aged↗

PubMed2005

Prospective study of estramustine phosphate for hormone refractory prostate cancer patients following androgen deprivation therapy.

INTRODUCTION: Estramustine phosphate (EMP) in combination with other cytotoxic agents has been widely used in clinical trials as an anti-tumor agent for the treatment of hormone-refractory prostate cancer (HRPC). However, few prospective studies have considered the efficacy of EMP monotherapy for HRPC patients following androgen-deprivation therapy (ADT), given the availability of methods to measure prostate-specific antigen (PSA) levels in the serum. We therefore initiated a prospective study to determine whether EMP is efficient for HRPC following ADT using changes in PSA levels as the major endpoint. METHODS: After a diagnosis of anti-androgen withdrawal syndrome had been excluded, 34 patients with HRPC who showed an elevated serum PSA level in 3 or more sequential tests following ADT were treated orally with 560 mg/day of EMP. The clinical stage and the median PSA value for inclusion in the study were D2 and 25.9 (range 6.5-540.8) ng/ml, respectively. Treatment was continued until evidence of disease progression reappeared or until severe adverse effects appeared. RESULTS: Of the 34 patients enrolled, 29 were evaluated, while the other 5 (15%) patients were discontinued due to severe gastrointestinal side effects. Seven of the 29 patients (24%) showed a decrease of 50% or greater in serum PSA levels from the initially elevated values, with the median duration of PSA response being 8.0 (range 2.2-18.8) months. Baseline PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase, performance status, and length of time of initial hormonal treatment did not correlate with the PSA response. With a median follow-up time of 20.0 (range 3.2-45.6) months, the cancer-specific survival rate at 2 years was 83% in the PSA responders and 44% in the non-responders. The PSA response was correlated with cancer-specific survival (p = 0.029). CONCLUSIONS: Following ADT one quarter of HRPC patients responded to EMP, with more than 50% of patients showing a decrease in PSA levels and an enhanced survival rate.

Adenocarcinoma↗

PubMed1997

Simultaneous antiandrogen withdrawal and treatment with ketoconazole and hydrocortisone in patients with advanced prostate carcinoma.

BACKGROUND: Although antiandrogen withdrawal has moderate efficacy in patients with hormone refractory prostate carcinoma (HRPC), the effect of the simultaneous suppression of adrenal androgens with ketoconazole at the time of antiandrogen withdrawal is not known. METHODS: Twenty consecutive patients with HRPC who had developed progressive disease despite combined androgen blockade were treated with antiandrogen withdrawal and simultaneous ketoconazole as a means of inhibiting adrenal steroid production. Prostate specific antigen (PSA) response was defined as a > 50% fall in PSA from baseline that was maintained for at least 8 weeks. RESULTS: Ten patients had established metastatic disease, 2 had high PSAs and no imaging studies (PSA of 70 and 160 ng/mL, respectively), 3 had microscopically positive lymph nodes and serologic progression, and 5 had serologic progression alone. Overall, of 20 evaluable patients, 11 (55%) had a > 50% fall in PSA (95% confidence interval [CI], 31.5-76.9%). The median PSA response duration was 8.5 months (95% CI, 7-17 months). The median survival was 19 months. Toxicity was mild, with Grade 1 and 2 nausea and emesis in 15% of patients, Grade 1 fatigue in 10% of patients, and reversible Grade 1 or 2 hepatotoxicity in 10% of patients. Mild skin toxicity was observed in 20% of patients. CONCLUSIONS: The addition of ketoconazole and hydrocortisone to antiandrogen withdrawal appears to increase the PSA response proportion observed with antiandrogen withdrawal alone. Toxicity is mild.

Adrenal Cortex Hormones↗

PubMed2004

Randomized Phase II trial assessing estramustine and vinblastine combination chemotherapy vs estramustine alone in patients with progressive hormone-escaped metastatic prostate cancer.

Based on the results of combined data from three North American Phase II studies, a randomised Phase II study in the same patient population was performed, using combination chemotherapy with estramustine phosphate (EMP) and vinblastine (VBL) in hormone refractory prostate cancer patients. In all, 92 patients were randomised into a Phase II study of oral EMP (10 mg kg day continuously) or oral EMP in combination with intravenous VBL (4 mg m(2) week for 6 weeks, followed by 2 weeks rest). The end points were toxicity and PSA response in both groups, with the option to continue the trial as a Phase III study with time to progression and survival as end points, if sufficient responses were observed. Toxicity was unexpectedly high in both treatment arms and led to treatment withdrawal or refusal in 49% of all patients, predominantly already during the first treatment cycle. The mean treatment duration was 10 and 14 weeks, median time to PSA progression was 27.2 and 30.8 weeks, median survival time was 44 and 50.9 weeks, and PSA response rate was only 24.6 and 28.9% in the EMP/VBL and EMP arms, respectively. There was no correlation between PSA response and survival. While the PSA response in the patients tested was less than half that recorded in the North American studies, the toxicity of EMP monotherapy or in combination with VBL was much higher than expected. Further research on more effective and less toxic treatment strategies for hormone refractory prostate cancer is mandatory.

Administration, Oral↗

PubMed1995

Acquired cutaneous adherence in patients with androgen-independent prostate cancer receiving ketoconazole and doxorubicin: medication-induced sticky skin.

BACKGROUND: The phenomenon of sticky skin has been reported in patients with psoriasis who are receiving retinoids. OBJECTIVE: We describe therapy-induced sticky skin in eight patients receiving ketoconazole and doxorubicin for androgen-independent prostate cancer. METHODS: Patients were treated with oral daily ketoconazole (400 mg every 8 hours) and intravenous doxorubicin weekly (20 mg/m2 continuously for 24 hours). Thirty-nine patients were entered into the study; retrospective information regarding sticky skin was obtainable from 28 patients or their spouses. Prostate specific antigen (PSA) values were compared in patients with and without therapy-induced sticky skin. RESULTS: Eight patients (29%) described sticky skin. Six of these patients (75%) had a PSA response. Of the 20 patients without sticky skin a PSA response occurred in 12 (60%). CONCLUSION: Sticky skin occurred in patients with androgen-independent prostate cancer who were simultaneously receiving ketoconazole and doxorubicin. To our knowledge this unique skin manifestation of acquired cutaneous adherence has not been previously described in association with chemotherapeutic or antifungal agents. The pathogenesis of acquired cutaneous adherence in these patients might relate to therapy-induced elevation of endogenous retinoids. The similar PSA response rate in patients with or without sticky skin suggests that retinoids may not play an essential role in the mechanism of antitumor activity of ketoconazole and doxorubicin.

Adhesiveness↗

PubMed1998

Pyrazoloacridine for the treatment of hormone-refractory prostate cancer.

There is a pressing need for new agents for the treatment of hormone-resistant prostate cancer (HRPC). Pyrazoloacridine (PZA) has antitumor activity in several in vitro and in vivo tumor systems, and was selected for testing in clinical trials by the National Cancer Institute (NCI). We conducted a phase II trial of PZA for the treatment of HRPC. Seventeen male patients with HRPC were treated with PZA at 750 mg/m2 i.v. given over a period of 3 hr every 3 weeks. Response to therapy was assessed with serial measurements of serum prostate-specific antigen (PSA) and sequential imaging studies. The 17 patients were treated and fully evaluable. One patient experienced a significant decrease in PSA, from over 10,000 ng/ml to 423 ng/ml, along with an improvement in bone scan findings. However, no other patient obtained an objective or PSA response (overall PSA response rate = 5.9%). Median survival duration was 15.3 months. Toxicity was moderate. If PSA is used as a marker of response, single-agent PZA appears to lack efficacy in the treatment of HRPC. However, the one unambiguous response, and the favorable toxicity profile observed, may warrant further evaluation of this agent.

Acridines↗

PubMed2005

A study from the EORTC new drug development group: open label phase II study of sabarubicin (MEN-10755) in patients with progressive hormone refractory prostate cancer.

Sabarubicin (MEN-10755), a new synthetic anthracycline analogue, was evaluated for safety and efficacy in a multicentre phase II study in patients with advanced hormone refractory prostate cancer (HRPC). Thirty seven patients were included, of which 34 were evaluable for PSA response according to Bubley's criteria. Sabarubicin was administered as a short (30 min) intravenous infusion at a dose of 80 mg/m(2) every 3 weeks. The main toxicity consisted of grade 3/4 neutropenia in 24 patients (64.9%), with grade 3/4 febrile neutropenia occurring in one patient only. Grade 3/4 cardiotoxicity was observed in 4 patients including one ineligible. Other toxicities were mild. Nine patients achieved a PSA response (26.5%), 10 patients had stable disease (29.4%) and 14 patients disease progression (41.2%). One patient (2.9%) had a PSA response that was not confirmed by repeat PSA testing. The objective response rate according to RECIST criteria was 6.7% in 15 patients with measurable disease. The median duration of PSA responses was relatively long 7.1 months (95% CI 4.9-20.7) as was the median time to treatment progression in patients with stable disease. The median overall survival was 18.7 months (95% CI 9.1-N), comparable to results recently observed in taxotere-containing regimens. To confirm and extend these results, further testing of sabarubicin in larger trials is warranted.

Aged↗

PubMed2004

Capecitabine in hormone-resistant metastatic prostatic carcinoma - a phase II trial.

The objective of the trial is to evaluate the efficacy of capecitabine in patients with metastatic hormone-resistant prostate carcinoma (HRPC), in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score) and its safety profile. In all, 25 patients with HRPC were enrolled on a phase II trial of capecitabine (Xeloda) at a dose of 1250 mg m(-2) orally twice daily on days 1-14 every 21 days. The inclusion criteria were PSA serum levels >3 x upper limit of normal, a WHO performance status 0-2, age <85 years and adequate bone marrow, liver and renal function. In patients with grade 2 or higher haematological toxicity on day 1 of the treatment cycle, therapy was first delayed, and then continued at a lower dose. Trial end points were PSA response and clinical benefit defined by quality of life (QL) data and analgesic consumption. The median age of patients was 70 years (range 54-85 years). A median of three cycles of capecitabine was administered (range 1-8). PSA response was observed in three patients (12%, 95% CI 3-31%), with times to tumour progression of 18, 21 and 35 weeks, respectively. In these patients, the response durations were 12, 17 and 32 weeks, respectively. Minor PSA regression was also seen in two further patients. The median time to tumour progression of all patients was 12 weeks (95% CI 9-15 weeks). Haematological toxicity was minor, with leukopenia grade 3 observed in one patient. There were three deaths during trial treatment, respectively, due to sepsis following mucositis and leukopenia, presumed sepsis with mucositis induced by chemotherapy and concomitant radiotherapy and cerebral dysfunction progressing to coma. Hand-foot syndrome grades 2 and 3 were observed in four patients each. Clinical benefit was observed in five patients (20%, CI 7-41%). Based on toxicity data, we recommend a lower starting dose of 1000 mg x m(-2) orally twice daily. While capecitabine has some activity in HRPC, as suggested by observed PSA responses, we conclude that it is not worthwhile to investigate capecitabine monotherapy in a phase III trial. Combinations of capecitabine with other agents, such as vinorelbine or docetaxel, may prove to be more effective.

Aged↗

PubMed2003

Nilutamide as second line hormone therapy for prostate cancer after androgen ablation fails.

PURPOSE: We investigate the prostate specific antigen (PSA) response rate with nilutamide as a second line hormonal agent in patients with advanced prostate cancer in whom androgen ablation failed. MATERIALS AND METHODS: From 1998 to 2001, 28 patients with hormone resistant prostate cancer were treated with nilutamide as second line hormonal therapy. Average patient age +/- SD was 72.9 +/- 9.1 years. Median time from diagnosis of cancer to hormone failure was 48 months (range 2 to 120). Median followup from initiation of nilutamide therapy was 26 months (range 15 to 44). All patients had previously received at least 1 antiandrogen (flutamide or bicalutamide) in addition to medical or surgical castration, which failed. RESULTS: Upon initiation of nilutamide therapy 18 of the 28 patients (64%) had an initial reduction in PSA and 8 (29%) sustained a PSA response (greater than 50% decrease) beyond 3 months (range 3 to 21). PSA response to nilutamide in patients with a previous antiandrogen withdrawal response versus nonresponse was 100% and 18%, respectively. In 10 of the 28 patients, (36%) PSA continued to increase. Interstitial pneumonitis developed, in 1 patient and 5 had nonspecific complaints (headaches, nausea, dizziness). During followup 6 of the 28 patients died 1 of whom was a nilutamide responder. No patient died while on nilutamide. CONCLUSIONS: Nilutamide can achieve a significant sustained PSA response with a favorable toxicity profile. Patients with a previous antiandrogen withdrawal response have a significantly greater chance of responding to nilutamide.

Aged↗

PubMed2002

(IN)-efficacy of salvage radiotherapy for rising PSA or clinically isolated local recurrence after radical prostatectomy.

PURPOSE: To determine the efficacy of external beam radiotherapy (RT) as salvage treatment for prostate-specific antigen (PSA) failure or local recurrence after radical prostatectomy. METHODS AND MATERIALS: Between 1991 and 1997, 98 patients underwent salvage RT to the prostatic bed at the Toronto Sunnybrook Regional Cancer Centre for PSA failure or local recurrence after radical prostatectomy. Thirty-six patients were treated for persistently detectable postoperative PSA levels (Group A), 26 for a delayed PSA rise (Group B), and 36 for palpable and/or biopsy-proven local recurrence (Group C). None had clinically apparent distant metastasis at the time of salvage RT. Freedom from PSA failure was defined as the maintenance of PSA <or=0.2 ng/mL. Cox regression analyses were performed to identify factors predictive of relapse. RESULTS: The median follow-up from radical prostatectomy and RT was 5.11 and 4.21 years for Group A, 5.31 and 3.32 years for Group B, and 7.85 and 3.95 years for Group C, respectively. The initial PSA response rate was encouraging at a range of 86-94%. The complete PSA response rate (PSA <or=0.2 ng/mL) was lower, however and ranged from 53% to 62%. The actuarial relapse-free rate, including freedom from PSA failure, at 4 years was 26%, 39%, and 14% for Groups A, B, and C, respectively. At the time of the last follow-up, 49, 20, and 1 patient had PSA failure alone, distant metastasis, and local progression, respectively. The actuarial survival rate at 4 years was 89%, 95%, and 94% for Groups A, B, and C, respectively. On Cox regression analysis, the significant predictors for relapse were PSA level before salvage RT and Gleason score for Group A, none for Group B, and margin status for Group C. CONCLUSION: The efficacy of salvage RT for PSA failure or local recurrence after RT was limited, reflected by very low relapse-free rates. Salvage RT appeared more efficacious for patients with a delayed PSA rise than for those with either persistently detectable postoperative PSA levels or clinically palpable local recurrence. Other strategies such as a combination of salvage RT and hormonal therapy need to be explored.

Aged↗