First-line Docetaxel-based Chemotherapy Research Articles

Association of changes in measurable disease by RECIST with survival in metastatic castration-resistant prostate cancer (mCRPC).

186 Background: In men with mCRPC receiving chemotherapy, measurable disease response by World Health Organization criteria has been demonstrated to be prognostic for overall survival (OS). We aimed to explore the association of changes in measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) with OS. Methods: Data from the control arm (n=612) of the phase III VENICE trial receiving docetaxel plus prednisone combined with placebo were available. Data on baseline clinical and laboratory variables were obtained in addition to outcome measures: best RECIST 1.0 response, PSA response and OS. Cox proportional hazards regression was used to evaluate the prognostic ability of RECIST-defined changes for OS using a 90-day landmark analysis. Results: 363 of 612 patients (59.3%) had measurable lesions, of whom 296 were evaluable for landmark analysis. 28 (9.5%) had progressive disease (PD) prior to day 90, while 58 (19.6%) had unconfirmed partial response (PR), i.e. declines ≥30% of the sum of diameters of target lesions. Median OS beyond day 90 for men with PR, stable disease (SD), and PD was 28.3, 23.3, 11.4 months, respectively (P < 0.001). In a multivariable analysis adjusting for pain, PCWG-2 subtype, type of progression (PSA vs. other), Gleason Score (≤ 7 vs. > 7), PSA, derived neutrophil-lymphocyte ratio, ECOG performance status and alkaline phosphatase, the hazard ratio (HR) for OS for patients with PR was 0.64 (95% CI 0.42 – 0.99, P = 0.045) compared to those without PR, and 1.78 (95% CI 1.07 – 2.95, P = 0.026) for those with PD compared to those without PD. PD remained significant (HR = 1.85, 95% CI 1.10 – 3.12, P = 0.020) after adjusting for PSA changes, but PR (P = 0.14) did not. Conclusions: In men with mCRPC receiving first-line docetaxel-based chemotherapy PR and PD by RECIST 1.0 within 90 days were associated with longer or shorter OS, respectively. Given the more frequent detection of measurable disease with current imaging, the accrual of patients with measurable tumors in phase II trials to assess RECIST changes may provide an objective signal of efficacy of new drugs.

Radiographic progression by Prostate Cancer Working Group (PCWG)‐2 criteria as an intermediate endpoint for drug development in metastatic castration‐resistant prostate cancer

To investigate the association of radiographic progression defined by Prostate Cancer Working Group (PCWG)-2 guidelines and overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC). Two trials that used PCWG-2 guidelines to define progression were analysed: a randomized phase II trial (n = 221) comparing first-line docetaxel-prednisone plus AT-101 or placebo, and a phase III trial (n = 873) comparing prednisone plus sunitinib or placebo after docetaxel-based chemotherapy. Cox proportional hazards regression models were used to estimate the association of radiographic progression with OS. Landmark analyses compared progressing patients with those who had not progressed. Sub-analyses compared patients removed from trial for progression vs other reasons. An increased risk of death was seen for radiographic progression at landmark times from 6 to 12 months with docetaxel-based therapy (hazard ratio [HR] >1.7 at all time-points). An increased risk of death was also seen with post-docetaxel prednisone alone or with sunitinib for progression at landmark times from 2 to 8 months (HR >2.7 at all time-points). Kendall's τ was 0.50 (P < 0.001) in the setting of docetaxel-based therapy and 0.34 (P < 0.001) in the post-docetaxel setting for association between radiographic progression and death amongst patients with both events. Removal from study due to radiographic progression was associated with a significantly lower OS compared with removal for other reasons in both trials. Limitations of a retrospective analysis apply and there was no central radiology review. Radiographic progression by PCWG-2 criteria was significantly associated with OS in patients with mCRPC receiving first-line docetaxel-based chemotherapy or post-docetaxel therapy. With external validation as a surrogate endpoint in trials showing survival benefits, the use of radiographic progression-free survival may expedite drug development in mCRPC, which has been hampered by the lack of intermediate endpoints.

Potential value of rapid prostate-specific antigen decline in identifying primary resistance to abiraterone acetate and enzalutamide.

To identify factors predicting primary resistance to new-generation hormonal agents (NHAs), abiraterone acetate and enzalutamide in patients with castration-resistant prostate cancer (CRPC). Our hospital has conducted two successive named patient NHA programs. A total of 57 patients with progressive CRPC previously treated with first-line docetaxel-based chemotherapy received standard NHA doses: abiraterone acetate 1000 mg once-daily combined with prednisone (5 mg twice daily) or enzalutamide 160 mg once-daily. Patients, who were assessed monthly to check their hematological parameters and prostate-specific antigen (PSA) levels, also underwent imaging investigations every 3-4 months. In total, 24 variables were assessed as potential predictors of primary NHA resistance. Univariate analysis indicated that baseline pain and lactate dehydrogenase levels, and PSA levels after 1 month's treatment were predictive of primary NHA resistance. Only the predictive value of PSA levels after 1 month of treatment was confirmed at multivariate analysis. This factor strongly predicted progression-free and overall survival. RESULTS suggest the use of a simple and rapid method of identifying patients with primary resistance to NHAs: patients not achieving a ≥ 50% reduction in PSA levels within the first treatment month should undergo intensive investigations to verify whether they have primary resistance to NHAs.

Biochemical and Objective Response to Abiraterone Acetate Withdrawal: Incidence and Clinical Relevance of a New Scenario for Castration-resistant Prostate Cancer

To describe the incidence and clinical relevance of biochemical and objective responses to abiraterone acetate (AA) withdrawal (AAWD) in patients with castration-resistant prostate cancer (CRPC). Twenty-six patients with progressive CRPC treated with first-line docetaxel-based chemotherapy were administered with AA at the standard dose of 1000 mg/day in combination with prednisone until progression. The patients were regularly followed up during treatment and after AAWD. Nineteen of the 26 patients discontinued AA because of progression. Three of the patients undergoing AAWD experienced a biochemical response, which was accompanied by a metabolic and radiological response as revealed by choline positron emission tomography in 2 cases. Regardless of the underlying molecular bases, AAWD response does not occur rarely. It is sometimes long-lasting and accompanied by a metabolic and radiographic improvement. AAWD response should be taken into account when further therapeutic strategies are planned in patients with CRPC with progressive disease during abiraterone therapy.

Reduction in serum clusterin is a potential therapeutic biomarker in patients with castration‐resistant prostate cancer treated with custirsen

Elevated levels of clusterin (CLU), a stress-induced and secreted cytoprotective chaperone, are associated with advanced tumor stage, metastasis, treatment resistance, and adverse outcome in several cancers. Custirsen, a second-generation antisense oligonucleotide, inhibits CLU production in tumor cells and reduces serum CLU levels. A Phase 2 study evaluated custirsen in combination with second-line chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC) who had progressed while on or within 6 months of first-line docetaxel-based chemotherapy. Exploratory analyses evaluated serum CLU levels during custirsen treatment and correlative clinical effects on prostate-specific antigen (PSA) response, overall survival, and any relationship between serum CLU and PSA. Men with mCRPC were treated with mitoxantrone/prednisone/custirsen (MPC, n = 22) or docetaxel retreatment/prednisone/custirsen (DPC plus DPC-Assigned, n = 45) in an open-label, multicenter study. Subject-specific profiles of PSA and serum CLU levels during treatment were characterized using statistical modeling to compute subject-specific summary measures; these measures were analyzed for relationship to survival using proportional hazard regression. Estimated individual serum CLU response profiles were scored as below or at/above the median level for the population through 100 days postrandomization. Median survival was longer for subjects scoring below the median serum CLU level compared with subjects at/above the median level, respectively (MPC: 15.1 months vs. 6.2 months; DPC-Pooled: 17.0 months vs. 12.1 months). Lowered serum CLU levels during custirsen treatment when in combination with either chemotherapy regimen were predictive of longer survival in mCRPC. These results support further evaluation of serum CLU as a therapeutic biomarker.Aside from PSA, there are currently no other prognostic or predictive biomarkers that can be used to guide treatment response in metastatic castration resistant prostate cancer (mCRPC). In a Phase 2 study, men with mCRPC were treated with prednisone and custirsen plus either mitoxantrone or docetaxel retreatment. Statistical modeling was used to compute subject-specific summary measures of PSA and serum clusterin levels at baseline and at Day 100 of treatment, followed by a regression analysis to evaluate relationship to overall survival. In this analysis, reduced serum clusterin levels during treatment were predictive of longer survival. These results currently support further evaluation of serum clusterin as a therapeutic biomarker in three ongoing Phase 3 clinical trials.

Efficacy and safety of docetaxel-based chemotherapy in Japanese men over 80 years old with castration-resistant prostate cancer.

e16094 Background: Docetaxel-based chemotherapy is widely used to treat castration-resistant prostate cancer (CRPC). However, its efficacy in elderly males has not yet been fully elucidated. In Japan, the number of elderly CRPC patients continues to increase. Therefore, it is urgently necessary to evaluate the effect of docetaxel-based chemotherapy in elderly Japanese men with CRPC. Methods: Sixty-eight male patients with CRPC who were treated with first-line docetaxel-based chemotherapy in a single institution from 2006 to 2011 were evaluated retrospectively. Results: The median age was 72.4 ± 6.5 years. Ten patients (14.7 %) were ≥ 80 years old (older group), and 58 (85.3 %) were &lt; 80 years old (younger group). All patients received docetaxel at a dose of 75 mg/m2 once every 3 weeks, and prednisolone 10 mg was given every day orally. The prostate-specific antigen (PSA) levels of the older and younger groups before docetaxel-based chemotherapy were 41.2 ± 37.4 ng/ml and 106.5 ± 184.7 ng/ml, respectively (P = 0.273). The PSA doubling times before docetaxel-based chemotherapy were 91.6 ± 92.6 days and 92.5 ± 91.9 days, respectively (P = 0.977). The performance status of the older group was 0 or 1. In the same group, 7 patients (70.0%) achieved a PSA decline of ≥ 30% and 4 patients (40.0%) achieved a PSA decline of ≥ 50%. In the younger group, the PSA decline was ≥ 30% in 37 patients (63.8%) and ≥ 50% in 26 patients (44.8%). The PSA decline rates of ≥ 30% and ≥ 50% were not significantly different between the two groups (p = 0.68 and p = 0.75, respectively). Progression-free survival (PFS) was also not significantly different between the two groups (PFS 5.3 vs. 7.3 months, p = 0.39). The major grade 3–4 toxicities were myelosuppression. Grade 3/4 neutropenia occurred in 80.0% of the older group and 78.0% of the younger group, and Grade 4 neutropenia occurred in 20.0% of the older group and 24.2% of the younger group. There were no significant differences between the two groups (Grade 3/4; p = 0.89, Grade 4; p = 0.79). Conclusions: Docetaxel-based chemotherapy showed a significant effect with a tolerable adverse event rate in elderly Japanese males over 80 years old with castration-resistant prostate cancer.

901PD - Association of Progression by Prostate Cancer Working Group (PCWG)-2 Criteria and Survival in Metastatic Castration Resistant Prostate Cancer

ABSTRACT Background Intermediate endpoints to identify active agents for metastatic castration-resistant prostate cancer (mCRPC) are suboptimal. The Prostate Cancer Working Group (PCWG)-2 guidelines recommend time to clinical or radiographic event endpoints, and discouraged use of endpoints using PSA changes. We investigated the association of progression defined by PCWG-2 guidelines and overall survival (OS). Methods Two trials were analyzed: CS-205, a randomized phase II trial (n = 221) comparing first-line docetaxel-prednisone (DP) plus AT-101 or placebo, and SUN-1120 (n = 873), a phase III trial comparing prednisone plus sunitinib (SP) or placebo (PP) following docetaxel-based chemotherapy. Both trials continued therapy until progression defined by PCWG-2 criteria and OS was the primary endpoint. OS was derived by the Kaplan-Meier method. Cox proportional hazards regression models were used to estimate the effect of progression on OS. Landmark analyses at 2-month intervals compared patients with prior progression with those without progression. Sub-analyses compared patients removed from trial for progression vs. other reasons and examined the association of type of progression with OS. Results Patients who had previously progressed had an increased risk of death. In CS-205, the hazards ratio (HR) ranged from 2.31 to 3.43 between landmark times of 6 to 12 months and in SUN-1120 HR was 2.75 to 5.21 between landmark times from 2 to 8 months. Median OS was 5.5 versus 14.4 months in CS-205 beyond month 6 and 7.1 versus 16.1 months in SUN-1120 beyond month 2 for those with/without prior progression. The types of progression associated with OS varied between the trials. Patients removed from study due to progression (excluding death) had a significantly worse OS than those coming off for other reasons (HR: 1.90, 95% CI: 1.26-2.87 in CS-205 and HR: 1.23, 95% CI: 1.02-1.48 in SUN-1120). Conclusions Progression by PCWG-2 criteria was significantly associated with decreased OS in patients receiving first-line docetaxel-based chemotherapy or post-docetaxel therapy. Further validation will facilitate the employment of PCWG-2 defined progression as an intermediate endpoint. Disclosure G. Sonpavde: Research support to institution from Ascenta Therapeutics and Pfizer, Inc, B.A. Wood: Employee of Ascenta Therapeutics, S. Wang: Employee of Pfizer, Inc, J. Paolini: Employee of Pfizer, Inc, M. Lechuga: Employee of Pfizer, Inc, M.R. Smith: Research support to institution from Pfizer, Inc, M.D. Michaelson: Research support to institution from Pfizer, Inc, All other authors have declared no conflicts of interest.

Evaluation of oral chemotherapy with capecitabine and cyclophosphamide plus thalidomide and prednisone in prostate cancer patients

The aim of this study was to evaluate clinical outcomes of second-line chemotherapy with capecitabine and cyclophosphamide (CTX) plus thalidomide and prednisone in refractory advanced castrate-resistant prostate cancer (CRPC) patients. We retrospectively reviewed patients with advanced CRPC who had previously progressed to first-line docetaxel-based chemotherapy. Patients were given second-line chemotherapy with capecitabine and CTX plus thalidomide and prednisone throughout the course. Patients were evaluated for response and toxicity, and treatment was continued until the disease progression or excessive toxicity was noted. From April 2007 to February 2010, a total of 28 patients (median age, 72.8 ± 2.9 years) received second-line chemotherapy. The median cycle and duration of metronomic chemotherapy were six (range: 1-12) cycles and 6.3 (range 1.5-20.5) months, respectively. Prostatic-specific antigen was decreased by more than 50% in 10 (35.7%) of the 28 patients. All patients had bone metastases, and 8 patients (28.6%) had measurable soft tissue lesions. Among the 8 patients, 1 patient achieved partial response, and 3 patients had stabilized disease. With a median follow-up time of 29.5 (95% CI, 26.4-33.4) months, median composite progression-free survival and overall survival were 4.7 (95% CI, 3.4-5.7) months and 19.5 (95% CI, 18.9-25.5) months, respectively. No grade 3-4 toxicity was observed, and none of the patients experienced grade 3-4 hematological and nonhematological toxicities. These data suggested that oral combination second-line chemotherapy with capecitabine and CTX plus thalidomide and prednisone offers promising activity with an excellent safety profile for patients with advanced CRPC.

Role of Androgen Deprivation Treatment in Patients With Castration-Resistant Prostate Cancer, Receiving Docetaxel-Based Chemotherapy

To assess the impact of continued androgen deprivation therapy (ADT) in patients with castration-resistant prostate cancer (CRPC) receiving first-line docetaxel-based chemotherapy. A retrospective review was performed on 78 patients fulfilling the criteria for CRPC who were treated with docetaxel-based chemotherapy over 5 years. Thirty-nine patients received concurrent ADT (ADT group), whereas 39 patients discontinued ADT (No-ADT group). PSA response rates were 66.7% for ADT patients and 48.7% for No-ADT patients (P = 0.27). The median progression-free survival and overall survival were 5.0 months and 24.8 months for ADT patients and 4.9 months and 22.1 months for No-ADT patients, respectively (P = 0.57, P = 0.94). Follow-up testosterone levels were available in 13 patients of the No-ADT group and none of them recovered a normal serum testosterone level over a median follow-up duration of 8.3 months from ADT discontinuation. ADT was recommenced in 21 of 39 patients in the No-ADT group and, of these, 6 (29%) achieved a PSA response. Clinical outcomes were not significantly different when patients with CRPC received concurrent ADT, or were not so treated, when receiving first-line docetaxel-based chemotherapy. Despite ADT withdrawal, serum testosterone level did not recover to the noncastrated level during the period of chemotherapy, and reinduction of hormone sensitivity occurred in about one-quarter of patients.

The interval from the last cycle of docetaxel-based chemotherapy to progression is associated with the efficacy of subsequent docetaxel in patients with prostate cancer

There is currently no standard treatment after first-line docetaxel-based chemotherapy for patients with castration-refractory prostate cancer (CRPC). Some patients are likely to discontinue first-line docetaxel-based chemotherapy because of either completed treatment or the occurrence of manageable side-effects. The aim of this study was to determine whether a rechallenge with docetaxel might be appropriate in patients with CRPC previously treated with docetaxel. Between December 2004 and July 2009, 39 patients diagnosed with metastatic cancer prostate at the Institut Gustave Roussy were administered subsequent docetaxel after front-line docetaxel-based chemotherapy. The medical records of these patients were extracted from the database. The PSA response rate (PSA decline ⩾30% and ⩾50%), progression-free survival (PFS) and overall survival (OS) of patients receiving docetaxel as a subsequent line of therapy were evaluated using consensus criteria. The effect of pre-treatment variables on efficacy was studied. A PSA decline ⩾30% and ⩾50% was observed in 64% and 38% of patients, respectively, median PFS was 4.3 months [confidence interval (CI) 95%: 3.6–4.9] and median OS was 15.8 months (CI 95%: 11.7–20.3) in 39 patients who received subsequent docetaxel. The interval between the last cycle of first-line docetaxel and progression [median: 3.0 months; range: 1–30 months] was associated with PFS: median PFS was 3.4 months (CI 95%: 2.6–4.1) and 6.3 months (CI 95%: 3.0–5.6), respectively, in patients with an interval <3.0 months and an interval ⩾3.0 months, ( p = 0.04). Tolerance of re-treatment with docetaxel was acceptable with no toxicity-related death. Re-treatment with subsequent docetaxel in patients with CRPC pretreated with first-line docetaxel is safe and demonstrates some activity. The interval from the last cycle of first-line docetaxel-based chemotherapy to progression is associated with the efficacy of subsequent docetaxel.

Docetaxel first-line therapy in HER2-negative advanced breast cancer: a cohort study in patients with prospectively determined HER2 status

Docetaxel is one of the most active cytotoxic drugs against breast cancer, but data are lacking on specific activity in molecularly selected subgroups. This retrospective study was aimed at assessing the outcome and prognostic factors for survival of patients with HER2-negative tumors receiving first-line docetaxel-based chemotherapy for advanced breast cancer (ABC). The medical charts of all 162 patients with prospectively proven HER2-negative ABC and having received docetaxel as first-line chemotherapy for metastatic disease at our institution were retrospectively reviewed with special emphasis on docetaxel efficacy. Potential prognostic factors were sought using multivariate analysis. Median progression-free survival (PFS) was 12 months (95% confidence interval 9.7-14.8) and median overall survival (OS) was 34.9 months (95% confidence interval 28.1-52.1). Hormone receptor (HR) status was the strongest prognostic factor in the univariate analysis for both PFS [hazard ratio = 0.23; P = 0.00000063] and OS (hazard ratio = 0.35; P = 0.0000079). After multivariate analysis, only three independent variables for PFS (HR-positive tumor, no prior adjuvant/neoadjuvant chemotherapy, and isolated bone metastases) and two for OS (HR-positive tumor and isolated bone metastases) remained predictive of a favorable outcome. HER2-negative, HR-positive ABC patients have a relatively good prognostic after docetaxel-containing first-line therapy. The subset of HER2-negative, HR-negative (triple-negative) has a very poor outcome, and innovative therapies are eagerly awaited for these patients.

7020 Performance status and interval from first-line docetaxel-based chemotherapy to progression are significant prognostic factors in patients with castration-resistant prostate cancer receiving second-line chemotherapy

7020 Performance status and interval from first-line docetaxel-based chemotherapy to progression are significant prognostic factors in patients with castration-resistant prostate cancer receiving second-line chemotherapy

Combining carboplatin and etoposide in docetaxel-pretreated patients with castration-resistant prostate cancer: a prospective study evaluating also neuroendocrine features

BackgroundThere is currently no standard treatment for patients with castration-resistant prostate cancer (CRPC) whose disease progresses after docetaxel-based chemotherapy. The purpose of this study was to prospectively assess the anticancer activity and tolerance of the carboplatin–etoposide combination in this setting while evaluating neuroendocrine (NE) features. Patients and methodsPatients with CRPC and metastases who experienced failure after first-line docetaxel-based chemotherapy were treated with carboplatin (area under the curve 5, day 1) and etoposide (80 mg/m2/day from days 1 to 3), repeated every 3 weeks. The association between serum chromogranin A (CgA), neuron-specific enolase (NSE), prostate-specific antigen-doubling time (PSADT), and treatment efficacy was studied. ResultsForty patients with CRPC who had received docetaxel with (n=20) or without (n=20) estramustine received the carboplatin–etoposide combination as second-line chemotherapy. A prostate-specific antigen (PSA) response defined as a PSA decline ≥50% was achieved in nine patients (23%). Median progression-free survival (PFS) was 2.1 months (range 0.6–9.6) and median overall survival was 19 months (range 2.1–27.7). Pain response was achieved in 15 (53%) of 28 assessable patients. Toxicity, including mainly grades 3–4 anaemia (25%) and febrile neutropenia in only 2% of patients, was manageable. Baseline CgA, NSE, or PSADT were not significant predictors for response or PFS. The PSA response rates were 18% and 31% in patients with normal and elevated serum CgA, respectively. It was 25% and 20%, respectively, in patients with normal and elevated serum NSE. ConclusionsCombining carboplatin and etoposide as second-line chemotherapy in patients with CRPC is active and well tolerated in spite of a limited PFS. Activity was observed in CRPC with and without NE features.

Docetaxel-Based Chemotherapy in Elderly Patients (Age 75 and Older) with Castration-Resistant Prostate Cancer

BackgroundThere are no data on the patterns of care and outcome of very elderly patients with castration-resistant prostate cancer (CRPC) treated with docetaxel. ObjectiveTo assess the routine use of first-line docetaxel-based chemotherapy in CRPC patients aged >75 yr. Design, setting, and participantsWe reviewed the clinical files of 175 patients aged ≥75 yr with CRPC treated with first-line docetaxel in nine French tertiary care cancer centres from 2000 to 2007. MeasurementsResponse rate, survival, and adverse events (AE). Results and limitationsMedian age was 78 yr. Ninety-five patients (54%) received a standard 3-wk regimen (SR), and 80 patients (46%) received an adapted regimen (AR) delivered on a weekly schedule with various times for rest periods. Patients treated with an AR were older (>80 yr) and had poorer performance status (PS; ≥2) than patients treated with the SR. The prostate-specific antigen (PSA) response rates were not significantly different between the standard and adapted treatment groups (71% vs 68%, p=0.79). The median progression-free survival (PFS) was 7.4 mo. The median overall survival (OS) was 15 mo. The incidence of grade 3 or 4 AEs was 46% and was correlated with poor PS and the presence of visceral disease but not with the regimen. Early discontinuation of treatment because of toxicity occurred more frequently in the AR group than in the SR group (30% vs 8.4%, p=0.0005). In multivariate analysis, only PS and the presence of visceral disease were predictors of OS. ConclusionsDocetaxel is active and feasible in elderly patients with good PS. The optimal treatment of frail patients with CRPC remains to be established. Geriatric tools should be used to more accurately detect elderly CRPC patients who are unfit for chemotherapy. Age by itself should not be used as a criterion to deny patients with CRPC a potentially effective chemotherapy.

A prospective study of carboplatin-etoposide in docetaxel-pretreated patients with hormone-refractory prostate cancer (HRPC): Clinical activity and correlation with neuroendocrine features

5151 Background: There is currently no standard of care for patients (pts) with HRPC and disease progression after docetaxel-based chemotherapy. Platin compounds have demonstrated activity in this setting and in vitro evidence of synergy between carboplatin and etoposide has previously been reported. A significant proportion of advanced HRPC exhibit neuroendocrine features but there are limited data on whether these patients should be treated differently or not. Methods: Pts with HRPC who experienced failure after first-line docetaxel-based chemotherapy were prospectively treated with carboplatin (AUC 5 day 1) and etoposide (80 mg/m2 day 1 to 3), repeated every 3 weeks as second-line chemotherapy. The response rate (defined as a serum PSA decline of = 50%), progression-free survival (PFS) and overall survival (OS) were evaluated using consensus criteria (Bubley JCO 1999). Pain relief was evaluated using a visual analogic scale. Serum chromogranin A and neurone specific enolase (NSE) levels were measured at baseline. Toxicity was evaluated according to NCI criteria. Results: Forty-one HRPC pts, previously treated with docetaxel with (n=24) or without (n=17) estramustine, prospectively received carboplatin-etoposide as second-line chemotherapy. A PSA response was obtained in 9 pts (22%). Pain relief was achieved in 18 pts (45%). Median progression-free survival was 9 weeks and median overall survival was 19 months. Toxicity included grade 3–4 anemia in 25% and febrile neutropenia in 2%. Biological neuroendocrine features (e.g. elevated baseline serum chromogranin A and NSE) were not associated with response or PFS. The response rate was 18% and 31% in pts with normal and elevated baseline chromogranin A, respectively. Conclusions: The carboplatin-etoposide regimen is active and well-tolerated as second-line chemotherapy after docetaxel-based chemotherapy in HRPC patients. Activity was detected in both tumors with and without neuroendocrine features. No significant financial relationships to disclose.