Stefan A. Loening

Treatment of newly diagnosed metastatic prostate cancer patients with chemotherapy agents in combination with hormones versus hormones alone

A prospective trial from July 1976 to September 1980 by the National Prostatic Cancer Project randomized newly diagnosed metastatic prostate cancer patients to DES 1 mg orally three times daily or orchiectomy; or DES, 1 mg, three times daily, plus cyclophosphamide at 1 mg/m2 iv every three weeks, or cyclophosphamide 1 g/m2 iv every three weeks plus estramustine phosphate (Estracyt) at 600 mg/m2 orally daily in three divided doses. There were 246 patients evaluated for response of 301 entered. These consisted of 83 on the DES/orchiectomy arm, 77 on DES plus cyclophosphamide, and 86 on Estracyt plus cyclophosphamide. Objective response rates, initially evaluated at 12 weeks, were similar among the treatments. However, chemotherapy as used in this study early in the diagnosis of metastatic disease appears to exhibit an improved effect on overall survival compared to hormone therapy alone. Analysis within groups having pain versus no pain at entry revealed a marked advantage after 80 weeks for chemotherapy when pain was initially present and a slight advantage during treatment (throughout follow‐up) when the pain was absent. Median survival times were 92, 91, and 94 weeks, respectively, for the three treatments. The progression‐free interval for responders showed no difference between initial treatments, although nearly one half of the patients are still in remission; hence, further follow‐up will be essential. Side effects were not excessive for the chemotherapy treatment arms and patient compliance was good. This national multicenter trial provides the basis for further testing of chemotherapy agents at an earlier phase for patients with newly diagnosed metastatic prostate cancer.

Evaluation of Magnetic Fluid Hyperthermia in a Standard Rat Model of Prostate Cancer

PURPOSE To examine the feasibility and potential of magnetic fluid hyperthermia (MFH) as a minimally invasive method for hyperthermia treatment of prostate cancer. MATERIALS AND METHODS Orthotopic Dunning R3327 prostate tumors were induced in 20 male Copenhagen rats. The animals either received MFH treatment following intratumoral administration of magnetic fluids or were used as either tumor growth controls for determination of iron distribution in selected organs or as histologic controls without MFH treatment. The MFH treatments were carried out at 45 degrees C or 50 degrees C using an AC magnetic field applicator system designed for small animals. RESULTS Sequential treatments with MFH were possible following a single intratumoral injection of magnetic fluid. Intratumoral temperatures of 50 degrees C and more were obtained and were monitored online using fluoro-optic thermometry. Four days after MFH treatments, 79% of the injected dose of ferrites was still present in the prostate. CONCLUSIONS The successful intraprostatic nanoparticle infiltration and stable steady-state intratumoral treatment temperatures demonstrate the feasibility of MFH in a prostate cancer model. Efficacy and survival benefit must be confirmed in further experiments.

Extracorporeal Shock Wave Lithotripsy: Multicenter Study of Kidney and Upper Ureter Versus Middle and Lower Ureter Treatments

Six institutions throughout the United States participated in this study. Each center used a multifunctional flat table lithotriptor (Dornier MFL-5000) to treat 658 patients with kidney and upper ureteral stones (766 treatments) and 323 with middle and lower ureteral stones (391 treatments), for a total of 925 patients (1,157 treatments). Some patients received more than 1 treatment (that is the kidney and ureter), for a total of 981 patient events. Complete followup was available for 81% of the patients. The overall stone-free rate at followup of approximately 90 days was greater in the middle and lower ureter group (83%) than in the kidney and upper ureter group (67%). The proportion of single stones treated was greater for the former group (89.5%) than for the latter group (72%). A larger proportion (18%) of the middle and lower ureter group required 2 or more treatments to the targeted stone than did the kidney and upper ureter group (13%). Anesthesia was required or selected in only 26.7% of the kidney and upper ureteral stone patients and in 18.5% of those with middle and lower ureteral calculi, usually at the request of the patient or physician, or for performance of an adjunctive procedure. The relative safety of this treatment is demonstrated by a low overall rate of complications reported during and after treatment, including a ureteral obstruction rate of 2.1% for kidney and upper ureteral stones and 2.5% for middle and lower ureteral stones. There were no demonstrated trends in a review of laboratory data to suggest significant treatment side effects. The diastolic blood pressure increased to more than 95 mm. Hg after extracorporeal shock wave lithotripsy (ESWL*) in 6% of the kidney and upper ureteral and 4% of the middle and lower ureteral stone patients, while pretreatment hypertension resolved after ESWL in 11% of both groups. The results of this clinical evaluation indicate somewhat greater effectiveness for the specified indications of ESWL of stones in the ureter below the upper rim of the bony pelvis, as opposed to those in the kidney and upper ureter, with a low incidence of complications and side effects.

A comparison of estramustine phosphate and streptozotocin in patients with advanced prostatic carcinoma who have had extensive irradiation.

AbstractIn this second nationally randomized cooperative chemotherapy trial of the National Prostatic Cancer Project 125 patients with histologically confirmed progressing advanced carcinoma of the prostate (clinical stage D) who had had prior pelvic irradiation of at least 2,000R received as initial therapy 1 of 2 non-myelosuppressive agents—estramustine phosphate or streptozotocin—for comparison with patients randomized to receive standard treatment. Patients whose disease was progressive after 12 weeks on chemotherapy were crossed over to receive the alternate therapeutic agent. Response to treatment was evaluated in 105 patients on the basis of previously established and defined criteria.All known prognostic factors were comparable among the 3 treatment arms. The objective response rates to therapy were 19 per cent in the standard arm (stable only), 30 per cent in the estramustine phosphate arm (stable and partial regression) and 32 per cent in the streptozotocin arm (stable arm). Thus far, 4 patients...

Comparison of Estramustine Phosphate and Vincristine Alone or in Combination for Patients with Advanced, Hormone Refractory, Previously Irradiated Carcinoma of the Prostate

There were 121 men with hormonally refractory metastatic cancer of the prostate who were randomized to receive estramustine phosphate or vincristine, or the combination of these 2 agents. All patients had received prior radiation therapy (greater than 2,000 rad). There were 90 patients who could be compared for response. The objective response rates (partial regression or stabilization of disease) for the 3 treatment groups were 26 per cent for estramustine phosphate, 24 per cent for estramustine phosphate plus vincristine and 15 per cent for vincristine. Subjective parameters varied little among the 3 regimens. The median duration of response for those responding to estramustine phosphate was similar (20 weeks) to that for vincristine (22 weeks) and greater than that for the combination (13 weeks). The probability of survival did not differ significantly for patients randomized to each of the 3 regimens. The addition of vincristine to estramustine phosphate did not enhance the response rate achieved by estramustine phosphate alone and vincristine alone produced the lowest response rate. Estramustine phosphate continues to be the most active agent in previously irradiated patients with hormonally refractory metastatic cancer of the prostate.

Gadolinium-enhanced three-dimensional magnetic resonance angiography versus conventional digital subtraction angiography: Which modality is superior in evaluating living kidney donors?

This study evaluates the correlation of magnetic resonance angiography (MRA) and digital subtraction angiography (DSA) with the operative vessel findings in living kidney donors. The intraoperative vessel findings of 52 living renal donors were compared with the preoperative diagnoses of each imaging technique. Sixty-seven arteries were found during explantation. Forty kidneys showed a single arterial blood supply, and 12 kidneys showed a multiple arterial blood supply. No advantage of either imaging method was found for arterial imaging. There were 55 veins identified during organ harvesting. MRA could not determine the venous system in one donor (1.9%) and failed to detect one small pole vein in another. DSA did not yield a venous diagnosis in seven patients (13.5%) and yielded misdiagnoses in four patients. The correct diagnosis of renal donor veins differed significantly in favor of MRA (kappa 0.79 vs. 0.45; P=0.008). MRA is superior to DSA in assessing the renal vasculature in living kidney donors.

Different stability of free and complexed prostate-specific antigen in serum in relation to specimen handling and storage conditions

Abstract The effect of sample collection, storage conditions (time and temperature), and freeze-thaw cycles on the stability of free prostate-specific antigen (fPSA), PSA complexed with α1-antichymotrypsin (ACT-PSA), and total PSA (tPSA) in serum was studied. The analytes were quantified using immunoassays for tPSA and fPSA on the Elecsys system 2010 and a research assay for ACT-PSA on the ES system (Roche Diagnostics). The stability of the analytes was calculated as percentages of the values measured in samples 1 h after blood collection. When the samples were stored at 37 °C, at room temperature or at 4 °C, the stability of ACT-PSA was less impaired than that of fPSA. To avoid erroneous results in the determination of PSA isoforms and their corresponding ratios, serum samples should be preserved at 4 °C when the analysis is performed within 8 h after blood collection, or they should be stored at −80 °C if the analysis is not feasible during that period.

Comparison of the clinical validity of free prostate-specific antigen, alpha-1 antichymotrypsin-bound prostate-specific antigen and complexed prostate-specific antigen in prostate cancer diagnosis.

Objective: To evaluate the diagnostic utility of free prostate specific antigen (fPSA), alpha–1– antichymotrypsin–bound PSA (PSA–ACT), complexed PSA (cPSA), and including their associated ratios to total PSA (tPSA) in serum for discrimination between prostate cancer (PCa) and benign prostatic hyperplasia (BPH). Methods: A total of 166 white men (age: 65–88 years) with a tPSA between 2 and 20 µg/l were retrospectively analysed. Serum concentrations of tPSA, fPSA, PSA–ACT and cPSA were measured in 118 untreated PCa patients and 48 patients with BPH. The tPSA and cPSA concentrations were measured with the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, USA). The Elecsys system 2010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and fPSA. The PSA–ACT assay is a newly, developed prototype assay on the ES system (Roche Diagnostics, Mannheim, Germany). Results: For statistical analysis only patients with tPSA between 2 and 20 µg/l were enrolled. The median concentrations of tPSA (Bayer: PCa 7.36 µg/l, BPH 4.03 µg/l; Roche: PCa 7.75, BPH 4.13), PSA–ACT (PCa 6.98, BPH 3.18) and cPSA (PCa 6.46, BPH 3.20) were significantly different. The median ratios of fPSA/tPSA (PCa 12.8 vs. BPH 22.4%), PSA–ACT/tPSA (PCa 89.8 vs. BPH 76.1%) and cPSA/tPSA (PCa 90.5 vs. BPH 81.7%) were significantly different between PCa and BPH patients. Using the areas under the curves, receiver operating characteristics analysis (tPSA: 2–20 µg/l) for discrimination between PCa and BPH showed that the ratios fPSA/tPSA (area under the curve: 0.77), PSA–ACT/tPSA (0.72) and cPSA/tPSA (0.78) were significantly different from tPSA (Bayer: 0.53; Roche: 0.55). PSA–ACT (0.64) and cPSA (0.59) alone were not significantly different from tPSA. The calculated ratios fPSA/tPSA, PSA–ACT/tPSA and cPSA/tPSA were not significantly different. Conclusion: The determination of PSA–ACT or cPSA and the associated ratios do not improve the diagnostic impact to discriminate between PCa and BPH compared to fPSA/tPSA ratio. The ratios PSA–ACT/tPSA or cPSA/tPSA can be considered to be alternative tools of fPSA/tPSA.

Different prostate-specific antigen assays give different results on the same blood sample: an obstacle to recommending uniform limits for prostate biopsies

To show the effect of different results for total prostate specific antigen (tPSA) and percentage free/total PSA (%fPSA) obtained with different assays for differentiating between benign and malignant prostate diseases.

Tumor M2 Pyruvate Kinase in Plasma of Patients with Urological Tumors

The M2 isoenzyme of pyruvate kinase (M2-PK) is specifically expressed in tumor cells (TU M2-PK) and may therefore provide a tumor marker for malignancies. We have investigated the plasma concentrations of TU M2-PK in patients with renal cell carcinoma (RCC), transitional cell carcinoma of the bladder (BCA), prostate cancer (PCA) and benign prostatic hyperplasia (BPH). TU M2-PK was quantified with a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Using this ELISA kit, plasma samples of 57 healthy individuals were compared to 63 patients with RCC, 36 patients with BCA, 58 patients with PCA and 28 patients with BPH. Patients with carcinomas were subdivided into those patients with nonmetastatic and those with metastatic disease. Only patients with RCC (nonmetastatic and metastatic) showed significantly increased concentrations of TU M2-PK compared to normal individuals. In metastatic RCC, TU M2-PK levels were highest and were also significantly enhanced compared to nonmetastatic RCC. The sensitivity for nonmetastatic RCC was 27.5% and for metastatic RCC 66.7% at the 95% reference value of the control group. In BCA, PCA and BPH, no significant differences could be detected. Our results indicate that TU M2-PK concentrations in plasma may be a potential biomarker of advanced RCC.