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Eric J Small

Publications and source records attributed to Eric J Small.

At least 55 records · Page 3Linked to original sources
PubMed2005

Prognostic significance of plasma chromogranin a levels in patients with hormone-refractory prostate cancer treated in Cancer and Leukemia Group B 9480 study.

OBJECTIVES: To test the hypothesis that chromogranin A (CgA) levels are prognostic in patients with metastatic hormone-refractory prostate cancer (HRPC). The extent of neuroendocrine differentiation in prostate cancer correlates with aggressive disease and with progression to HRPC. Plasma CgA levels in patients with prostate cancer may reflect the extent of the tumor neuroendocrine phenotype. METHODS: Pretreatment plasma was collected from 390 patients with metastatic HRPC enrolled in the Cancer and Leukemia Group B (CALGB) 9480 trial, a study of three different doses of suramin. Plasma CgA levels were determined in 321 samples in duplicate using a quantitative sandwich immunoassay. The proportional hazards model was used to assess the prognostic significance of CgA in predicting overall survival. RESULTS: The median plasma CgA level was 12 U/L (interquartile range 7.7 to 19.3). In univariate analysis, plasma CgA correlated inversely with survival times, with a survival time of 17 months for low CgA (less than 12 U/L, 95% CI 14 to 19) compared with 11 months for high CgA (95% CI 8 to 14, P = 0.014) and at all exploratory cutpoints, including CgA of 9.5 U/L or less versus greater than 9.5 U/L, with survival of 19 months compared with 12 months (P = 0.0015). In multivariate models (adjusting for performance status, prostate-specific antigen, and lactate dehydrogenase), the plasma CgA levels remained predictive of overall survival. CONCLUSIONS: These results support the hypothesis that serum CgA levels correlate with outcome in patients with HRPC, although the clinical significance needs to be established in confirmatory studies before incorporation of CgA measurements in clinical practice.

Adenocarcinoma↗
PubMed2005

Progress in detection and treatment of prostate cancer.

PURPOSE OF REVIEW: The purpose of this review is to highlight the most important developments in the diagnosis, prevention, and management of prostate cancer reported in the past year that have been published in the medical literature. RECENT FINDINGS: Recent research has shown that clinically meaningful prostate cancer can develop in patients with a PSA value <4 ng/dL and has suggested that 'watchful waiting' approaches may not be appropriate for young patients or those with a life expectancy of greater than 15 years. The contribution of obesity to high-grade disease and a higher rate of relapse has also been described. There is now randomized data suggesting that adjuvant hormonal therapy for as little as six month's time confers a survival benefit for those receiving radiation therapy. Secondary hormonal manipulation with ketoconazole is now supported by randomized phase III data. Most importantly, this year the results of two randomized phase III clinical trials of chemotherapy in hormone refractory prostate cancer have shown that survival can be increased by 20% with the use of docetaxel. SUMMARY: Recent data reported in the past year have significant implications for those involved in the management of prostate cancer. The results of the chemotherapy trials have resulted in new standards of care for this disease.

Antineoplastic Agents, Hormonal↗
PubMed2005

High-dose etoposide, thiotepa, and dose-adjusted carboplatin (TVCa) with autologous hematopoietic stem cell rescue as treatment of relapsed or refractory germ cell cancer.

A phase I/II trial with high-dose etoposide, thiotepa, and dose-adjusted carboplatin (TVCa) with autologous hematopoietic stem cell rescue (AHSCT) as treatment for patients with relapsed or refractory germ cell cancer was investigated. The phase I portion involved a dose escalation schema for carboplatin and thiotepa while keeping the dose of etoposide constant. The intended carboplatin dose was adjusted for renal function based on the glomerular filtration rate. The phase II portion of the trial evaluated the efficacy, feasibility, and safety of tandem TVCa with AHSCT. Twenty-four patients with relapsed or refractory germ cell cancer were treated in this phase I/II trial. Nine of 24 (38%) achieved a complete response. With a median follow up of 71 months (range,1-108 months), all 9 of 24 (38%) are alive and continuously disease-free. There were 2 (7%) treatment-related deaths. The median time to an absolute granulocyte count greater than 0.5 x 10/L was 11 days (range, 9-20 days) on phase I and 10 days (range, 9-13 days) on phase II therapy. The median time to a platelet count greater than 20 x 10/L was 15 days (range, 12-40 days) on phase I and 14 days (range, 13-27 days) on phase II therapy. Nonhematologic toxicity was mild to moderate. A significant correlation was seen between intended carboplatin dose and actual AUC. TVCa high-dose chemotherapy is active and well tolerated in patients with relapsed or refractory germ cell cancer.

Adult↗
PubMed2005

Update on chemotherapy for advanced bladder cancer.

PURPOSE: Recent years have seen several advances in the treatment of locally advanced and metastatic bladder cancer. We summarize the current state of the art for advanced bladder cancer treatment. MATERIALS AND METHODS: A comprehensive review of published, prospective phase II/III clinical trials and retrospective analyses of patients with advanced bladder cancer was performed. RESULTS: Adjuvant and neoadjuvant chemotherapeutic strategies around the time of radical cystectomy have been used to decrease the risk of subsequent metastatic disease. Although the benefit of adjuvant chemotherapy remains unproven, neoadjuvant chemotherapy is associated with a modest 5% to 6% absolute survival benefit in 2 meta-analyses of the available data. Chemoradiation is feasible and effective in some patients, allowing bladder preservation with an acceptable risk of progression. Randomized, phase III data comparing methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy to gemcitabine/cisplatin showed similar response proportions and overall survival with less toxicity in the gemcitabine/cisplatin arm. This has led to the widespread use of gemcitabine/cisplatin as first line chemotherapy for metastatic bladder cancer. The optimal agents and regimens for second line chemotherapy remain undefined. Similarly biological and targeted therapies for advanced bladder cancer remain investigational. CONCLUSIONS: Combination cisplatin based neoadjuvant chemotherapy may benefit patients with locally advanced bladder cancer. Gemcitabine/cisplatin has replaced methotrexate, vinblastine, doxorubicin and cisplatin as the regimen of choice in patients with good renal function. The optimal regimens for the medically unfit patient and second line chemotherapy remain undefined. The development of targeted therapies, less toxic regimens and improved cytotoxic agents are necessary to improve outcomes.

Carcinoma, Transitional Cell↗
PubMed2005

Lifestyle correlates of health perception and treatment satisfaction in a clinical cohort of men with prostate cancer.

There is a growing need to understand how nutritional and lifestyle practices may optimize quality of life (QOL) and health after diagnosis for the 1.5 million men living with prostate cancer in the United States. We are establishing a clinical cohort of men with prostate cancer at the University of California San Francisco. Men completed detailed dietary and lifestyle questionnaires annually and provided consent for blood and tissue specimens to be stored for research if they underwent radical prostatectomy. We examined the feasibility of establishing this cohort and analyzepreliminary baseline data on participant demographics, lifestyle habits, and QOL using c2 and t-tests and logistic regression models. Between February 2002 and July 2004, we enrolled 343 men with prostate cancer into the survey portion of this cohort. The response rate was approximately 85% via in-clinic enrollment and 30% via mail enrollment. Based on analysis of the first 193 men enrolled, there was a high level of treatment satisfaction in this population (88% of men were satisfied or extremely satisfied with treatment) and positive reports of general health perception (73% of men perceived themselves to be in excellent [34%] or very good [39%] health). Whether treatment interfered with diet was an independent predictor of health perception and treatment satisfaction. Use of dietary supplements was high (90%) in this well-educated population. In conclusion, we demonstrated good feasibility for conducting this longitudinal study and observed initial indications that diet and other lifestyle practices were important predictors of patient QOL.

Aged↗
PubMed2005

Antigen-presenting cells 8015 (Provenge) in patients with androgen-dependent, biochemically relapsed prostate cancer.

BACKGROUND: Antigen-presenting cells 8015 (APC8015; Provenge) is an immunotherapeutic product designed to initiate a T-cell-mediated immune response against prostatic acid phosphatase, an antigen overexpressed in 95% of prostate cancer cells. In phase I/II trials, APC8015 has shown immunologic and clinical responses in patients with androgen-independent prostate cancer. This phase II trial was conducted to assess the prostate-specific antigen (PSA)-modulating effects of APC8015 in patients with androgen-dependent prostate cancer (ADPC) with biochemical progression. PATIENTS AND METHODS: Patients with nonmetastatic recurrent disease as manifested by increasing PSA levels (0.4-6.0 ng/mL) and who had undergone previous definitive surgical or radiation therapy were enrolled. Therapy consisted of APC8015 infusion on weeks 0, 2, and 4 (ie, 3 infusions). Prostate-specific antigen was measured at baseline and monthly until disease progression, defined as a doubling of the baseline or nadir PSA value (whichever was lower) to > or = 4 ng/mL or development of distant metastases. RESULTS: Thirteen of 18 patients demonstrated an increase in PSA doubling time (PSADT), with a median increase of 62% (4.9 months before treatment vs. 7.9 months after treatment; P = 0.09; signed-rank test). CONCLUSION: Therapy was well tolerated. APC8015 as single-agent immunotherapy for patients with ADPC and biochemical progression did not result in > or = 50% decrease in PSA from baseline levels but did appear to modulate PSADT in some patients. Further manipulations of host immunity may be required to achieve a significant antitumor effect.

Adenocarcinoma↗
PubMed2005

Prior estrogen therapy as a predictor of response to subsequent estramustine-based chemotherapy in patients with androgen-independent prostate cancer.

BACKGROUND: Hormone-refractory prostate cancer (HRPC) has modest response rates to second-line estrogenic agents such as diethylstilbestrol and the herbal product PC SPES. Estramustine phosphate (EMP) is a microtubule inhibitory agent with estrogenic properties commonly used in patients with metastatic HRPC. To determine whether previous response to second-line estrogen therapy would predict subsequent response to EMP-based chemotherapy, a retrospective study was conducted. PATIENTS AND METHODS: Patients with HRPC previously treated with second-line estrogenic therapy who subsequently received EMP-based chemotherapy were enrolled in a retrospective analysis. The progression of disease or response to treatment was determined with use of standard prostate-specific antigen (PSA) criteria and Response Evaluation Criteria in Solid Tumors. RESULTS: Seventy-eight patients were included in the analysis. Twenty-five patients with disease progression after receiving estrogen therapy received subsequent EMP-based chemotherapy. Overall, initial PSA response to any estrogen therapy was 54%. The overall PSA response to EMP-based chemotherapy was 60%, and the objective response was 36%. The PSA response to subsequent EMP-based chemotherapy was independent of patients having a previous response to estrogen therapy (70% vs. 53%; P = 0.68). The median overall survival for patients receiving estrogenic therapy and subsequent EMP-based chemotherapy was 12.7 months. CONCLUSION: Previous response to second-line hormonal maneuvers with estrogen therapy does not predict subsequent response to EMP-based chemotherapy.

Antineoplastic Agents, Hormonal↗
PubMed2004

Quality of life impact of three different doses of suramin in patients with metastatic hormone-refractory prostate carcinoma: results of Intergroup O159/Cancer and Leukemia Group B 9480.

BACKGROUND: Research has suggested that men with hormone-refractory prostate carcinoma have a lower quality of life (QOL) compared with men who have hormone-sensitive prostate carcinoma and that quality of life (QOL) steadily declines over the last year of life for men with prostate carcinoma. The primary purpose of the current study was to evaluate whether there was evidence of palliative effects associated with suramin at any of the three doses administered in the original clinical trial. METHODS: Patients with histologically confirmed advanced hormone-refractory adenocarcinoma of the prostate were randomized to receive suramin at a low dose (n = 129; median age, 69 years), an intermediate dose (n = 129; median age, 71 years), or a high dose (n = 127; median age, 70 years) as part of the Intergroup 0159/Cancer and Leukemia Group B 9480 trial. Patients completed a battery of assessment tools, including the Functional Assessment of Cancer Therapy (FACT)-Prostate, the Center for Epidemiological Studies-Depression Scale (CES-D), the Brief Pain Inventory, and an opioid medication log, at baseline, on Day 1 of the sixth week of active therapy, during the second week after treatment termination, and 3 months after administration of the final suramin dose. RESULTS: Patients who received low-dose suramin reported improvement in QOL (FACT-General: P < 0.01; FACT-Treatment Outcome Index: P < 0.01) and decreased levels of depression (CES-D: P < 0.0006) during treatment compared with patients in the intermediate- and high-dose arms. After treatment, all groups experienced equal decreases in FACT and CES-D scores. CONCLUSIONS: The pattern of results suggests that the lowest dose of suramin administered had a palliative effect in terms of improvement in QOL and decreased levels of depression and that this effect was lost once suramin was discontinued.

Adenocarcinoma↗
PubMed2004

Biology and clinical development of vascular endothelial growth factor-targeted therapy in renal cell carcinoma.

PURPOSE: To review the biology of renal cell carcinoma (RCC) leading to vascular endothelial growth factor (VEGF) overexpression and the clinical results of VEGF blockade in metastatic RCC. METHODS: A review of relevant published literature regarding VEGF, von Hippel-Lindau (VHL) gene inactivation and VEGF overexpression in RCC was performed. Further, a review of the mechanism, toxicity, and clinical development of VEGF-targeted therapy in metastatic RCC was undertaken. RESULTS: VEGF is the major proangiogenic protein that exerts a biologic effect through interaction with cellular receptors. The majority of sporadic clear-cell RCC tumors are characterized by VHL tumor suppressor gene inactivation. The resulting VHL gene silencing leads to VEGF overexpression. An antibody to VEGF (bevacizumab) has demonstrated a significant prolongation of time to disease progression compared with placebo in patients with metastatic RCC. Small molecules with inhibitory effects against the VEGF receptor have undergone initial clinical testing in metastatic RCC with substantial objective response rates. CONCLUSION: Therapeutic targeting of VEGF in RCC has strong biologic rationale and preliminary clinical efficacy. Further investigation will determine the optimal timing, sequence, and utility of these agents in RCC.

Adenocarcinoma, Clear Cell↗
PubMed2004

Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer.

BACKGROUND: Mitoxantrone-based chemotherapy palliates pain without extending survival in men with progressive androgen-independent prostate cancer. We compared docetaxel plus estramustine with mitoxantrone plus prednisone in men with metastatic, hormone-independent prostate cancer. METHODS: We randomly assigned 770 men to one of two treatments, each given in 21-day cycles: 280 mg of estramustine three times daily on days 1 through 5, 60 mg of docetaxel per square meter of body-surface area on day 2, and 60 mg of dexamethasone in three divided doses before docetaxel, or 12 mg of mitoxantrone per square meter on day 1 plus 5 mg of prednisone twice daily. The primary end point was overall survival; secondary end points were progression-free survival, objective response rates, and post-treatment declines of at least 50 percent in serum prostate-specific antigen (PSA) levels. RESULTS: Of 674 eligible patients, 338 were assigned to receive docetaxel and estramustine and 336 to receive mitoxantrone and prednisone. In an intention-to-treat analysis, the median overall survival was longer in the group given docetaxel and estramustine than in the group given mitoxantrone and prednisone (17.5 months vs. 15.6 months, P=0.02 by the log-rank test), and the corresponding hazard ratio for death was 0.80 (95 percent confidence interval, 0.67 to 0.97). The median time to progression was 6.3 months in the group given docetaxel and estramustine and 3.2 months in the group given mitoxantrone and prednisone (P<0.001 by the log-rank test). PSA declines of at least 50 percent occurred in 50 percent and 27 percent of patients, respectively (P<0.001), and objective tumor responses were observed in 17 percent and 11 percent of patients with bidimensionally measurable disease, respectively (P=0.30). Grade 3 or 4 neutropenic fevers (P=0.01), nausea and vomiting (P<0.001), and cardiovascular events (P=0.001) were more common among patients receiving docetaxel and estramustine than among those receiving mitoxantrone and prednisone. Pain relief was similar in both groups. CONCLUSIONS: The improvement in median survival of nearly two months with docetaxel and estramustine, as compared with mitoxantrone and prednisone, provides support for this approach in men with metastatic, androgen-independent prostate cancer.

Adenocarcinoma↗
PubMed2004

Prospective, multicenter, randomized phase II trial of the herbal supplement, PC-SPES, and diethylstilbestrol in patients with androgen-independent prostate cancer.

PURPOSE: To evaluate the herbal combination, PC-SPES, and diethylstilbestrol (DES) in patients with androgen independent prostate cancer (AIPC). PATIENTS AND METHODS: A randomized phase II study was conducted with cross-over design. Patients were randomly assigned to receive either three PC-SPES capsules orally three times a day or DES 3 mg orally once a day. Prophylactic warfarin was administered. At clinical or prostate-specific antigen progression, patients received the other therapy. The study closed prematurely after PC-SPES was withdrawn from the market. Chemical analyses were performed on multiple lots of PC-SPES. RESULTS: Ninety patients were enrolled, of whom 85 were assessable for response. Prostate-specific antigen declines > or = 50% were noted in 40% (95% CI, 25% to 56%) with PC-SPES, and 24% (95% CI, 12% to 39%) with DES. Median response duration was not reached with PC-SPES, and was 3.8 months with DES. Median time to progression for randomly assigned patients was 5.5 months for PC-SPES and 2.9 months for DES. Common toxicities included mild fatigue, gynecomastia, and mastodynia. Five thromboembolic events occurred (one PC-SPES, four DES). Responses in the cross-over phase were inconclusive. Four lots of PC-SPES had measurable quantities of DES, ranging from 0.01% to 3.1% of the dose used in the DES arm. Ethinyl estradiol was also detected in PC-SPES lots. CONCLUSION: PC-SPES and DES demonstrate activity in AIPC and are well tolerated. However, the synthetic estrogens, DES and ethinyl estradiol, were detected in various lots of PC-SPES, including those used in this trial. Clinical trials that utilize herbal therapies must account for issues of purity and consistency.

Administration, Oral↗
PubMed2004

Time to disease progression to evaluate a novel protein kinase C inhibitor, UCN-01, in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is characterized by von Hippel-Lindau gene inactivation and vascular endothelial growth factor (VEGF) overproduction. The mechanism of VEGF overproduction may involve protein kinase C (PKC) delta and zeta isoforms. UCN-01 (7-hydroxystaurosporine) is a selective inhibitor of PKC. Given the historically low objective response rate in RCC, time to disease progression (TTP) as an alternative endpoint was employed to evaluate the antitumor activity of UCN-01 in RCC. METHODS: Patients with progressive, metastatic RCC received UCN-01 intravenously on Day 1 of each 21-day cycle. The initial dose was 90 mg/m(2) and all subsequent doses were 45 mg/m(2) unless modified for toxicity. TTP was the primary endpoint, defined as the period from the first day of treatment until disease progression. Detection of circulating EpCAM-positive renal carcinoma cells was undertaken for predictive or prognostic potential. RESULTS: Twenty-one patients were enrolled in this Phase II study. Accrual was halted after failure to reach a predetermined efficacy requirement with 7 patients remaining disease progression free after 4 months (6 cycles). The median TTP for all patients was 2.67 months (range, 0.4-7.6 months). There were no objective responses. Therapy was generally well tolerated. Thirteen patients had < 0.6 EpCAM-positive cells/mL (considered negative) at all time points measured. Two patients had detectable EpCAM-positive cells at a single time point with other measurements being negative. CONCLUSIONS: TTP is a novel endpoint for the evaluation of agents in RCC. UCN-01 did not demonstrate significant antitumor activity. No evidence for significant circulating EpCAM-positive cells was found in this study cohort.

Adult↗
PubMed2004

Cancer and Leukemia Group B 90206: A randomized phase III trial of interferon-alpha or interferon-alpha plus anti-vascular endothelial growth factor antibody (bevacizumab) in metastatic renal cell carcinoma.

The majority of sporadic clear cell renal cell carcinoma (RCC) is characterized by loss of heterozygosity of the von Hippel-Lindau (VHL) tumor suppressor gene and somatic inactivation of the remaining VHL allele. The resulting VHL gene silencing leads to induction of hypoxia-regulated genes including vascular endothelial growth factor (VEGF). Thus, therapeutic inhibition of VEGF holds promise for treatment of this historically refractory malignancy. An antibody to VEGF (bevacizumab, Avastin) has demonstrated a significant prolongation of time to disease progression compared with placebo in patients with metastatic RCC. Interferon-alpha (IFN-alpha) is a standard initial cytokine therapy in RCC with a modest response rate and a survival advantage demonstrated in randomized trials. We hypothesized that the addition of anti-VEGF therapy to IFN-alpha would prolong survival in untreated metastatic RCC patients. A Phase III trial is now being conducted randomizing untreated, metastatic clear cell RCC patients to IFN-alpha alone or IFN-alpha plus Avastin.

Alleles↗
PubMed2004

Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583).

PURPOSE: Antiandrogen withdrawal (AAWD) results in a prostate-specific antigen (PSA) response (decline in PSA level of > or =50%) in 15% to 30% of androgen-independent prostate cancer (AiPCa) patients. Thereafter, adrenal androgen ablation with agents such as ketoconazole (K) is commonly utilized. The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy. PATIENTS AND METHODS: AiPCa patients were randomized to undergo AAWD alone (n=132), or together with K (400 mg orally [p.o.] tid) and hydrocortisone (30 mg p.o. each morning, 10 mg p.o. each evening; n=128). Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K. RESULTS: Eleven percent of patients undergoing AAWD alone had a PSA response, compared to 27% of patients who underwent AAWD and simultaneous K (P=.0002). Objective responses were observed in 2% of patients treated with AAWD alone compared to 20% in patients treated with AAWD/K (P=.02). There was no difference in survival. PSA and objective responses were observed in 32% and 7%, respectively, of patients receiving deferred K, and were more common in patients with prior AAWD response. Treatment with K was well tolerated, and resulted in a decline in adrenal androgen levels, which rose at the time of disease progression. CONCLUSION: K has modest activity in AiPCa patients, while AAWD alone has minimal activity. Adrenal androgen levels fall with treatment with K and then climb at the time of progression, suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of K.

Adenocarcinoma↗
PubMed2004

Safety and biological activity of repeated doses of recombinant human Flt3 ligand in patients with bone scan-negative hormone-refractory prostate cancer.

PURPOSE: The purpose of this study was to evaluate the safety, biological activity, and feasibility of repeated doses of the dendritic cell (DC)-stimulating agent Flt3 ligand (FL) in patients with bone scan-negative hormone-refractory prostate cancer. EXPERIMENTAL DESIGN: Thirty-one patients with hormone-refractory prostate cancer who had elevated prostate-specific antigen (PSA) levels and negative bone scans were enrolled. Six cycles (28 days each) were planned. In the first cycle, patients were randomized to FL or placebo. All patients received open-label FL during the next five courses. DC, anti-FL antibody, and PSA levels were measured every 15 days to assess biological activity. RESULTS: DCs increased markedly in FL-treated patients from precycle to day 15, and the increase was consistent in each cycle. Mean percentages of DCs in peripheral blood ranged from 1.4% to 1.9% precycle and from 10.1% to 13.9% on day 15, and after the first cycle, absolute counts on day 15 were approximately 29-fold higher than precycle levels. Natural killer cell counts (CD56(+)) were found to be elevated after cycle 1 (154% increase versus 2.8% decrease in placebo group at day 22). Twenty-two of 27 patients tested developed nonneutralizing anti-FL antibody. The most frequently experienced toxicity was injection site reaction, followed by asthenia, rash, and diarrhea. Although median PSA levels did not vary during any cycle, a significant slowing in velocity of PSA was observed while patients were on-study (relative velocity = 0.002) compared with prestudy PSA velocity (relative velocity = 0.007). CONCLUSIONS: FL was well tolerated. FL consistently produced an increase in DC count without any evidence of decreasing response with continued exposure. The expansion of DCs and the slowing of PSA velocity after administration of FL suggest potential clinical applications in the immunotherapy of prostate cancer.

Adult↗
PubMed2004

Eligibility and outcomes reporting guidelines for clinical trials for patients in the state of a rising prostate-specific antigen: recommendations from the Prostate-Specific Antigen Working Group.

PURPOSE: To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA). RESULTS HYPOTHESIS: A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population. PATIENT POPULATION: The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed. INTERVENTION: Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation. OUTCOMES: An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting: Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned. TRIAL DESIGN: The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer-specific survival; the time to development of metastatic disease is an alternative. CONCLUSION: Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.

Clinical Trials as Topic↗
PubMed2004

Impact of race on survival in men with metastatic hormone-refractory prostate cancer.

OBJECTIVES: To determine whether blacks with hormone-refractory prostate cancer have shorter survival compared with whites with the same disease. METHODS: Data from eight multicenter trials (four Phase II and four randomized Phase III studies) conducted by the Cancer and Leukemia Group B were combined. Eligible patients had progressive prostate cancer after androgen deprivation therapy (with documented castration levels of testosterone), an Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate hematologic, renal, and hepatic function. The proportional hazards model was used to assess the prognostic importance of race, adjusting for important factors. All statistical tests were two-sided. RESULTS: Of the 1183 patients, 15% were blacks, 45% of patients had a Gleason sum of 8 or greater, and the median age was 71 years. Of the 1183 patients, 35% had measurable disease and 89% had an Eastern Cooperative Oncology Group performance status of 0 to 1. Blacks were younger, had a shorter interval between diagnosis and study entry, and had greater prostate-specific antigen levels, lower hemoglobin levels, and a lower likelihood of prior prostatectomy than whites. The median survival was 15 months (95% confidence interval 12 to 18) for blacks compared with 14 months (95% confidence interval 13 to 15) for whites. In a multivariate analysis, adjusting for age, performance status, presence of visceral disease, hemoglobin, Gleason sum, prostate-specific antigen level, alkaline phosphatase, lactate dehydrogenase, and years since diagnosis, the hazard ratio was 0.85 (95% confidence interval 0.71 to 1.02, P = 0.08) for blacks compared with whites. CONCLUSIONS: No statistically significant difference was found in overall survival between blacks and whites with metastatic hormone-refractory prostate cancer.

Adenocarcinoma↗