Phase I trial of docetaxel with estramustine in androgen-independent prostate cancer.

PURPOSE: To evaluate the toxicity, efficacy, and pharmacokinetics of docetaxel when combined with oral estramustine and dexamethasone in a phase I study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Thirty-four men were stratified into minimally pretreated (MPT) and extensively pretreated (EPT) groups. Estramustine 280 mg PO tid was administered 1 hour before or 2 hours after meals on days 1 through 5, with escalated doses of docetaxel from 40 to 80 mg/m2 on day 2. Treatment was repeated every 21 days. RESULTS: Thirty-four patients were assessable for toxicity and 33 for response. In the MPT patients, dose-limiting myelosuppression was reached at 80 mg/m2, with six patients experiencing grade 3/4 granulocytopenia. In EPT patients, escalation above 70 mg/m2 was not attempted. Fourteen MPT (70%) and six EPT (50%) patients had a > or = 50% decline in serum PSA on two consecutive measurements taken at least 2 weeks apart. The overall 50% PSA response rate was 63% (95% confidence interval [CI], 28% to 81%). Of the 18 patients with bidimensionally measurable disease, five (28%; 95% CI, 11% to 54%) achieved a partial response. At the time of entry onto the study, 15 patients required narcotic analgesics for bone pain; after treatment, eight (53%) discontinued their pain medications. The area under the curve for docetaxel increased linearly from 40 to 70 mg/m2. At 80 mg/m2, the measured area under the curve was 8.37 (standard deviation, 0.724), which was significantly higher than the previously reported values. CONCLUSION: The recommended phase II dose of docetaxel combined with estramustine is 70 mg/m2 in MPT patients and 60 mg/m2 in EPT patients. This combination is active in men with androgen-independent prostate cancer.

Phase I/II studies of docetaxel (Taxotere) combined with estramustine in men with hormone-refractory prostate cancer.

Evaluation of the combined regimen of estramustine and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) in men with hormone-refractory prostate cancer is in its early stages. While this combination is promising in terms of efficacy, adverse events associated with estramustine are a concern. Estramustine has been associated with side effects such as nausea, vomiting, edema, and serious vascular events. Reported here are the results of phase I and phase II trials in which 280 mg estramustine was given three times daily on days I to 5 in 21-day treatment cycles with docetaxel at varying doses. Data from patients evaluable thus far support the efficacy of this combination, both in chemotherapeutically naive patients and in those who have had prior therapy. A survival benefit from this combination appears achievable from these early studies. As significant antitumor activity can be achieved with docetaxel alone, future studies need to define the minimal dose of estramustine for this combination.

Cyclosporine-associated end-stage nephropathy after cardiac transplantation: incidence and progression.

BACKGROUND: The salutary immunosuppressive effects of cyclosporine in extending cardiac allograft survival may be curtailed by its nephrotoxic effects. We reviewed our first 9 years of experience with cyclosporine after cardiac transplantation, to evaluate the incidence and progression of cyclosporine-associated end-stage renal failure necessitating chronic hemodialysis. METHODS: Retrospective computer-based file review and personal interview when possible. RESULTS: The population at risk was comprised of all adult cardiac recipients surviving at least 3 years (n=293). Of these, 19 (6.5%) developed end-stage renal failure requiring chronic hemodialysis. There were 17 men and 2 women (mean age of 45 +/- 11 years). The mean creatinine clearance for the study group decreased by 38% (P<0.001 vs. before transplant) by 6 months after transplantation and by 48% by 3 years postoperatively (P<0.001 vs. before transplant). The mean serum creatinine rose by 80% (P< 0.001 vs. before transplant) by 6 months after transplantation and by 125% by 3 years postoperatively (P<0.001 vs. before transplant). Time elapsed from transplantation to hemodialysis ranged from 3.7 to 9.5 years (mean 6.4 +/- 2). Actuarial 1- year survival after onset of hemodialysis was 75%. CONCLUSIONS: Although cyclosporine remains the central immunosuppressive agent for cardiac allograft recipients, its use leads to a greater than one-third decrease in creatinine clearance by 6 months after transplantation and progression to end-stage renal failure, requiring hemodialysis in 6.5% of cardiac transplant recipients. Moreover, these patients are at increased risk of death compared with other cardiac allograft recipients. This data warrants the search of alternative or adjunctive agents that would allow decreased dosing or reduced nephrotoxicity of cyclosporine, while maintaining equivalent survival.

Carcinoma of the lung after heart transplantation.

We have recently noted an unexpected high incidence of lung cancer in our population of cardiac allograft recipients. We conducted a retrospective review of cardiac transplantation at our institution to investigate the incidence, clinical course, and outcome of patients who developed lung cancer following heart transplantation. Nine patients--each with a history of smoking at 30 pack-years--developed lung cancer following heart transplantation, for an incidence of 1.56% of patients at risk. Eight of the patients were male > or = 50 years of age, representing 3.3% of the male transplant recipients in this age group. The interval from transplantation to diagnosis clustered around 3-5 years after transplantation, but in two instances (22%), a neoplasm was discovered within 6 months of transplantation. Almost half of the cancers were discovered incidentally, despite routine radiographic surveillance. Seven of 9 (78%) patients had stage IV disease at presentation. Median survival after diagnosis was 3 months, and five of the seven patients who died survived less than 4 months after diagnosis. We conclude that cardiac transplant recipients are at increased risk for development of lung cancer. Patients with a moderate to heavy smoking history might well be advised to undergo chest CT scanning in an aggressive search for occult lung cancer before cardiac transplantation is considered further. Finally, despite frequent radiologic examinations, these lung cancers are often diagnosed incidentally, are far advanced at the time of diagnosis, are not surgically resectable, and are poorly responsive to adjuvant therapy.

Mitral valve replacement and tricuspid valve repair after cardiac transplantation.

Efforts aimed at limiting the pool of cardiac retransplantation candidates have focused increasingly on attempts to preserve cardiac allograft function. The present report reviews the course of a patient who underwent mitral valve replacement and tricuspid annuloplasty for bivalvular incompetence after cardiac transplantation and examines the limited reported world experience with valve replacement after transplantation. The limited yet successful experiences with these and other operations in cardiac allograft recipients suggest that worsening donor organ shortages will likely lead to increased clinical experience with conventional operations in the transplanted heart.

[Shock caused by electrical current]. / Sok izazvan udarom elektricne struje.

The authors elaborate the most frequent causes of electroshock and consequences to the human body thereof. Recent advances in modern medical technology increase the hazard of the electroshock. Tissue burns, asphyxia, CNS destruction and ventricular fibrillation are possible consequences. Depending on the electric current strength, the organism may be a subject of either a macroshock or a microshock. The methods of microshock prevention in hospital environment are disclosed. Two patients are presented, being treated at the Institute of Anesthesiology and Intensive Care.

Hansenula anomala outbreak at a surgical intensive care unit: a search for risk factors.

During a 5-month period, Hansenula anomala (H. anomala), an opportunistic fungus, caused an outbreak of infections in eight adult patients treated at a surgical intensive care unit (ICU). The source of the infections and route of transmission could not be identified. A case-control study included 32 patients treated simultaneously at the surgical ICU. Univariate analysis pointed to the following significant risk factors: blood alkalosis, reduced urea, duration of hospitalization, bacteremia and colonization with Pseudomonas aeruginosa, and an APACHE II score >17 (during bacteremia or fungemia). The stepwise logistic regression multivariate analysis showed only the duration of blood alkalosis to be significant in case patients.

[Anesthesia in surgery of the veins]. / Anestezija pri operativnim zahvatima na venama.

Patients with varicose complex of low extremities do not present any special problem in anaesthesiology. Method recommended is inhalational anaesthetic, eadly mobilisation of patient and infusion of low molecular dextran, during and immediately after operative procedure. During thrombectomy from deep venous system there is real danger of pulmonary embolism. This group of patients has higher risk than former, too. Authors recommended their own method for prevention of preoperative centripetal mobilization of thrombus, using a standard Recklinhausen's cuff inflated against abdominal wall under a plexiglass plate.

Dexamethasone does not significantly contribute to the response rate of docetaxel and estramustine in androgen independent prostate cancer.

PURPOSE: We evaluated the independent response rate of dexamethasone before docetaxel and estramustine administration as measured by changes in serum prostate specific antigen (PSA) in patients with androgen independent prostate cancer. MATERIALS AND METHODS: A total of 12 patients received 20 mg. dexamethasone orally every 6 hours for 3 doses repeated every 3 weeks before starting cytotoxic therapy with estramustine and docetaxel. After progression on dexamethasone 280 mg. estramustine orally 3 times daily on days 1 to 5 and 70 mg./m.2 docetaxel intravenously for 1 hour on day 2 were given. RESULTS: None of the patients initially treated with dexamethasone monotherapy (median 1 cycle, range 1 to 5) had a PSA decline of 50% or greater. Median PSA increase on monotherapy was 47% (range 0% to 22%). On estramustine and docetaxel therapy PSA decreased 50% or greater in 11 patients (92%, 95% confidence intervals [CI] 60 to 99) and 80% or greater in 7 (58%, 95% CI 29 to 84), and normalized in 5 (42%, 95% CI 16 to 71), with a median duration of response of 153 (range 42 to 371), 132 (range 84 to 287) and 84 (range 21 to 174) days, respectively. Median times to reach 50% and 80% decreases in baseline PSA were 21 (range 21 to 209) and 63 (range 21 to 138) days, respectively. In 9 patients (75%, 95% CI 43 to 93) PSA decreased at least 50% by week 9. Of 4 patients with bidimensionally measurable disease 3 had a partial response. Median time to progression was 263 days (range 91 to 378). CONCLUSIONS: Administration of 20. mg. dexamethasone orally every 6 hours for 3 doses every 3 weeks does not significantly contribute to the PSA response rate of estramustine and docetaxel.