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Mario Eisenberger

Publications and source records attributed to Mario Eisenberger.

11 recordsLinked to original sources
PubMed2006

Time to prostate specific antigen recurrence after radical prostatectomy and risk of prostate cancer specific mortality.

PURPOSE: In patients treated with radical prostatectomy who have biochemical recurrence we have previously reported that time from surgery to biochemical recurrence and postoperative prostate specific antigen doubling time are significantly related to the risk of prostate cancer death. We performed a more thorough examination of the association of time from surgery to biochemical recurrence and the risk of prostate cancer death. MATERIALS AND METHODS: We retrospectively studied the records of 379 patients treated with radical prostatectomy between 1982 and 2000 who had had biochemical recurrence. We examined the association of time from surgery to prostate specific antigen recurrence and prostate specific antigen doubling time, and the risk of prostate cancer death using the Spearman correlation and Cox proportional hazards regression, respectively. RESULTS: Longer time from surgery to prostate specific antigen recurrence was associated with a slower prostate specific antigen doubling time (Spearman r = 0.36, p < 0.001) and a decreased risk of prostate cancer death (RR 0.76, 95% CI 0.66 to 0.88, p < 0.001). The 15-year actuarial prostate cancer specific survival rate after biochemical recurrence in patients with recurrence at 3 years or less was 41% (95% CI 29 to 53) compared to 87% (95% CI 75 to 93) in patients with recurrence more than 3 years after radical prostatectomy. On multivariate analysis a shorter time from surgery to prostate specific antigen recurrence was associated with an increased risk of prostate cancer death (3 or less vs more than 3 years, RR 2.70, 95% CI 1.37 to 5.31, p = 0.004). CONCLUSIONS: Earlier prostate specific antigen recurrence is associated with an increased risk of prostate cancer death. These data suggest that perhaps time to prostate specific antigen recurrence may be a reasonable intermediate end point in patients treated with radical prostatectomy, although this must be validated in other studies.

Aged↗
PubMed2005

Chemotherapy for hormone-refractory prostate cancer: now it's a question of "when?".

Recently, data from two randomized phase III studies that compared docetaxel-based chemotherapy to mitoxantrone-based therapy demonstrated that treatment with docetaxel can prolong life in a significant way for patients with hormone-refractory prostate cancer. For many patients who experience disease progression after androgen-deprivation therapy, however, chemotherapy may not be immediately indicated. Such cases include those individuals with hormone-refractory disease in the absence of clinical metastases, and those with asymptomatic metastatic disease, for example. As a result, clinicians treating patients with hormone-refractory disease must weigh the benefits of earlier chemotherapy against its risks, and may consider other therapies such as secondary hormonal approaches before initiating chemotherapy. This decision is further complicated by the fact that a phase III study designed to compare secondary hormonal therapy with chemotherapy has failed due to lack of accrual. Furthermore, the limitations of chemotherapy for prostate cancer are being clarified and include a lack of standard second-line therapy as well as uncertain benefits for those with nonmetastatic disease. In this review, we will highlight some of the issues that impact on the decision of when to start chemotherapy and in whom as well as the potential benefits of secondary hormonal approaches.

Antineoplastic Agents, Hormonal↗
PubMed2005

Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy.

CONTEXT: The natural history of biochemical recurrence after radical prostatectomy can be long but variable. Better risk assessment models are needed to identify men who are at high risk for prostate cancer death early and who may benefit from aggressive salvage treatment and to identify men who are at low risk for prostate cancer death and can be safely observed. OBJECTIVES: To define risk factors for prostate cancer death following radical prostatectomy and to develop tables to risk stratify for prostate cancer-specific survival. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 379 men who had undergone radical prostatectomy at an urban tertiary care hospital between 1982 and 2000 and who had a biochemical recurrence and after biochemical failure had at least 2 prostate-specific antigen (PSA) values at least 3 months apart in order to calculate PSA doubling time (PSADT). The mean (SD) follow-up after surgery was 10.3 (4.7) years and median follow-up was 10 years (range, 1-20 years). MAIN OUTCOME MEASURE: Prostate cancer-specific mortality. RESULTS: Median survival had not been reached after 16 years of follow-up after biochemical recurrence. Prostate-specific doubling time (<3.0 vs 3.0-8.9 vs 9.0-14.9 vs > or =15.0 months), pathological Gleason score (< or =7 vs 8-10), and time from surgery to biochemical recurrence (< or =3 vs >3 years) were all significant risk factors for time to prostate-specific mortality. Using these 3 variables, tables were constructed to estimate the risk of prostate cancer-specific survival at year 15 after biochemical recurrence. CONCLUSION: Clinical parameters (PSADT, pathological Gleason score, and time from surgery to biochemical recurrence) can help risk stratify patients for prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. These preliminary findings may serve as useful guides to patients and their physicians to identify patients at high risk for prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy to enroll them in early aggressive treatment trials. In addition, these preliminary findings highlight that survival in low-risk patients can be quite prolonged.

Aged↗
PubMed2005

Achieving treatment goals for hormone-refractory prostate cancer with chemotherapy.

The belief that hormone-refractory prostate cancer (HRPC) is a chemotherapy-resistant disease has been effectively refuted by the results of two recent randomized phase III trials. The TAX327 trial compared weekly docetaxel, every-3-weeks (Q3W) docetaxel, and Q3W mitoxantrone plus prednisone in 1,006 patients with HRPC, and results demonstrated that survival was significantly longer with a docetaxel-based regimen than with mitoxantrone. That trial demonstrated that only Q3W docetaxel was significantly superior to mitoxantrone with respect to overall survival. Quality of life was also superior in the docetaxel groups. In the Southwest Oncology Group (SWOG) 9916 trial, 674 men with progressive HRPC were randomized to 3-week cycles of docetaxel plus estramustine or mitoxantrone plus prednisone. Overall and disease-free survival times were significantly longer in the docetaxel arm. Collectively, the results of these trials demonstrate that survival can be significantly improved with chemotherapy in patients with HRPC to an extent that is comparable with the survival benefits seen in other cancers considered sensitive to chemotherapy such as breast cancer. Among various research tasks in HRPC is the definition of potential surrogate end points for survival, which will facilitate the conduct of pivotal trials. Prostate-specific antigen (PSA) response rate and changes in PSA constructs (i.e., PSA doubling time and PSA velocity) are promising potential surrogate end points for future trials and are being actively evaluated at the present time. Until there is clear demonstration of a surrogate role for these alternative end points, survival remains the appropriate end point for phase III trials in HRPC. There is a need for safe and effective second- and third-line regimens for patients progressing after docetaxel, and these patients should enter clinical trials designed for this population. Mitoxantrone, vinorelbine, the platinum analogue satraplatin, and epothilone are among compounds that require careful testing in this setting. The addition of targeted therapies, such as the endothelin receptor antagonist, atrasentan, and angiogenesis inhibitors, such as thalidomide and bevacizumab, to docetaxel-based therapy is being evaluated. High-dose calcitriol may also be an effective addition to docetaxel. The extensive effort devoted to the evaluation of chemotherapy and other systemic modalities of treatment of HRPC is likely to yield additional clinical benefit for patients, making HRPC a more manageable, less lethal, and less debilitating disease.

Antineoplastic Combined Chemotherapy Protocols↗
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

A phase II trial of temozolomide and IFN-alpha in patients with advanced renal cell carcinoma.

The combination of temozolomide (TEM) and interferon-alpha (IFN-alpha) previously demonstrated a 30% response rate in metastatic melanoma. A single institution, phase II trial evaluating the efficacy of TEM/IFN in patients with advanced renal cell carcinoma (RCC) was conducted. Safety and tumor response were the main outcomes. Eligible patients received 200 mg/m(2)/day TEM orally on days 1-5 every 28 days, with IFN 2.5 million U/m(2)/day subcutaneously (s.c.) three alternate days/week for days 1-15 first cycle, then 5 million U/m(2)/day s.c. 3 alternate days/week throughout each 28-day cycle. Efficacy was evaluated every 8 weeks, and dose-limiting toxicities (DLTs) were treated with dose reductions of the culprit drug. Sixteen patients (ages 37-67) were initially enrolled. Of the 14 evaluable patients, there was one minor response. Best response was stable disease, with 7 patients remaining on study for > or =6 months. Five were alive for more than 2 years, and 2 remain alive at 45 and 50 months after enrollment. DLTs included TEM-induced myelosuppression and IFN-induced fever/chills. Other toxicities were mild to moderate (grades 1-3). The combination of TEM/IFN proved quite tolerable. This regimen appears inactive in terms of response in this population with poor prognosis, but the patients with stable disease > or =6 months remain of interest.

Administration, Oral↗
PubMed2003

Ten-year survival in patients with metastatic prostate cancer.

The objective of this analysis is to identify baseline covariates that predict which patients will be long-term survivors with metastatic prostate cancer. We analyzed data from Southwest Oncology Group (SWOG) S8894, a clinical trial in men with newly diagnosed metastatic prostate cancer, to evaluate pretreatment characteristics associated with 10-year survival. There were 1286 eligible patients randomized to this study. Of these, 794 have been followed for > or = 10.5 years and are included in the analyses. Proportional odds models were used to predict 3 survival categories (survival for < 5 years, 5 up to 10 years, and > or = 10 years). Baseline patient and disease characteristics investigated were protocol treatment (flutamide vs. placebo), severity of disease, SWOG performance status (PS), bone pain, Gleason score, race, age, and prostate-specific antigen (PSA) level at study entry. Of the 794 evaluable patients, 77% lived < 5 years, 16% lived 5 up to 10 years, and 7% lived > or = 10 years. Factors predicting a statistical significant association with longer survival (P < 0.05) included minimal disease, better PS, no bone pain, lower Gleason score, and lower PSA level. All but PS were also significant in multivariate analyses. However, only 13% of patients (5 of 38) who lived > or = 10 years were correctly predicted in their survival category based on the model, whereas 98% (405 of 414) who died within the first 5 years were correctly predicted. Although statistically significant baseline characteristics were identified in this clinical trial, they did not accurately predict the survival interval to which a patient belonged.

Adenocarcinoma↗
PubMed2002

Short-term stability of the molecular forms of prostate-specific antigen and effect on percent complexed prostate-specific antigen and percent free prostate-specific antigen.

Differences in stability of the free and complexed molecular forms of prostate-specific antigen (PSA) may influence the clinical utility of assays for these forms, as well as the calculated ratios to total PSA (tPSA), such as percent free PSA (fPSA) and percent complexed PSA (cPSA). The objective of this study was to directly compare the short-term stability of fPSA and cPSA under different storage conditions. Specimens (3 with prostate cancer, 3 biopsy-negative without cancer, 2 normal) from 8 men were analyzed at baseline within 2 hours of collection, and at 4 hours, 8 hours, 24 hours, 48 hours, and 1 week after storage at room temperature, 4 degrees C, or -20 degrees C. Serum specimens were analyzed in duplicate on the Bayer Immuno 1 analyzer (tPSA, cPSA) and on the Beckman Coulter Access analyzer (tPSA, fPSA Tandem assays). Baseline tPSA values ranged from 0.7 to 62.0 ng/mL, with a median of 7.9 ng/mL (Immuno 1). Overall, all forms of PSA were stable up to 24 hours at the 3 temperatures, with the exception of fPSA and percent fPSA, which decreased when stored at 4 degrees C. After 1 week, tPSA levels decreased when stored at room temperature and at 4 degrees C, as did cPSA stored at room temperature. Over the 7 days, percent cPSA was stable at room temperature, but increased at 4 degrees C. There were no significant changes in any PSA form or calculated ratio with storage at -20 degrees C for up to 1 week. In summary, in the short term (<1 week), fPSA is less stable with storage than tPSA or cPSA in a time- and temperature-dependent fashion. Thus, specimen handling should be considered when interpreting PSA results. It is recommended that specimens not analyzed the same day (within 8 hours of collection) be stored frozen at -20 degrees C.

Cryopreservation↗
PubMed2002

Long-term effects of androgen deprivation therapy in prostate cancer patients.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers in men and has an increasing incidence. In 1999, 37 000 men died from PCa in the USA. Androgen deprivation therapy (ADT) with GnRH agonists is frequently employed in the treatment of recurrent and metastatic PCa by inducing medical castration, rendering these men hypogonadal. Because hypogonadism in men is associated with a wide range of complications, we attempted to determine the effects of long-term ADT in men with PCa. METHODS: We conducted a cross-sectional study at a tertiary care centre to determine the effect of ADT on lean body mass (LBM), muscle strength, bone mineral density (BMD), sexual function, and quality of life (QOL) in men with PCa. Three groups of men were enrolled: (1) 20 men with PCa who were undergoing medical castration with GnRH agonists for at least 12 months prior to the onset of the study (ADT group); (2) 18 age-matched men with nonmetastatic PCa who were post prostatectomy and/or radiotherapy but had not yet undergone ADT (non-ADT group); and (3) 20 age-matched normal men who were healthy and ambulatory (control group). RESULTS: Men on ADT had castrate levels of serum total testosterone (P < 0.0001), free testosterone (P < 0.0001) and oestradiol (P < 0.0001), which were significantly lower than in the other groups. Total body (P = 0.03) and lumbar spine (P < 0.0001) BMD was significantly lower in patients on ADT compared to other groups and was associated with higher levels of urinary N-telopeptide (P = 0.02). The ADT group had higher fat mass compared to the other groups (P = 0.0001) and significantly reduced upper body strength (P = 0.001) when compared to non-ADT patients. The ADT group had lower overall scores on Watt's Sexual Function Questionnaire compared to other groups (P = 0.0001), in particular a decrease in desire, arousal and frequency of spontaneous early morning erections. The ADT group also had lower overall QOL scores, resulting in significant limitation of physical function (P = 0.001), role limitation (P = 0.02) and perception of physical health (P = 0.004). CONCLUSIONS: This study suggests that osteoporosis, unfavourable body composition, sexual dysfunction and reduced quality of life are seen in patients receiving androgen deprivation therapy for at least 12 months. Longitudinal studies in this patient population will shed further light on the timing of the development and the extent of these complications. Meanwhile, this information will assist both physicians and patients with prostate cancer to make informed decisions regarding androgen deprivation therapy.

Aged↗