Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

PURPOSE: To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. PATIENTS AND METHODS: A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. RESULTS: Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. CONCLUSION: Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.

Standard interleukin-2 (IL-2) and interferon-alpha immunotherapy versus an IL-2 and 4-epirubicin immuno-chemotherapeutic association in metastatic renal cell carcinoma.

BACKGROUND: Recombinant human interleukin-2 (IL-2) has a well-documented anti-tumor activity against RCC and has demonstrated a synergistic anti-tumor activity between doxorubicin and IL-2, thus providing better survival. This study investigated the toxicity and efficacy of the association between doxorubicin and IL-2, and interferon-alpha, and the immuno-chemotherapeutic association with IL-2 and 4-Epirubicin. PATIENTS AND METHODS: Patients with histologic evidence of metastatic or advanced RCC were randomized to receive either IL-2 + IFN-alpha (Arm A) or IL-2 + 4-Epi (Arm B). Arm A patients received IFN-alpha subcutaneously at doses of 3 million UI on days 1, 3 and 5 for 6 weeks. Arm B patients received 4-EPI at doses of 25 mg/m2 on days 1, 8, 15, 22, 29 and 36. Treatment cycles were repeated at 10 week intervals. RESULTS: Of 38 evaluable patients, we observed 2 complete responses, 2 partial responses, 1 minimal response, 1 mixed response, 21 stationary disease and 11 disease progressions. There was no significant difference in overall survival between the two groups. However in arm B, the median overall survival for responding patients was better than that of patients who experienced a disease progression. Performance status was the only predictive prognostic factor. CONCLUSIONS: Our analysis confirms the low response rate associated with IL-2 treatments but seems to indicate a role of anthracycline in improving the survival of responding patients with an acceptable toxicity.

Experience with cyclosporine: approaching the therapeutic window for C2 levels in maintenance kidney transplant recipients.

This study was aimed to evaluate the clinical benefit of C2 monitoring in 191 stable renal transplant patients previously monitored by C0. All patients had been transplanted for at least 1 year and received cyclosporine (CsA)-based immunosuppression since the start. At the inceptions C0 levels were significantly correlated with C2 values (P<.0001). Patients with starting C2 levels >1000 ng/mL showed significantly higher levels of serum creatinine (sCr) both at inception (1.66 +/- 0.50 vs 1.44 +/- 0.41 mg/dL; P=.0021) and at the end of a 2-year follow-up (1.84 +/- 0.80 vs 1.46 +/- 0.51 mg/dL; P=.005). C2 monitoring revealed that a high percentage of patients were overexposed to CsA, mainly in the subgroup with most recent renal engraftments (12 to 24 months). The switch to C2 monitoring was associated with a slower deterioration of graft function (P=.02). Further, the mean values of C2 over a 2-year follow-up were inversely correlated with sCr at the end of follow-up (P=.0005). Finally, patients with mean threshold C2 levels above 720 ng/mL, roughly corresponding to the median value of C2, showed significantly lower levels of sCr at the end of follow-up (P=.0004). In conclusion, C2 monitoring of maintenance renal transplant patients allows one to identify a significant percentage of overexposed subjects, possibly limiting the rate of progression of chronic graft dysfunction. Target range values between 700 and 900 ng/mL appear to be associated with better long-term kidney graft function.

[Reconstruction with skin flaps of the posterior aspect of the thighs after total pelvic evisceration with removal of vulvo-perineal soft tissues in recurrent vulvar squamous carcinoma]. / Ricostruzione con lembi cutanei della faccia posteriore delle cosce dopo evisceratio pelvica totale con asportazione dei tessuti molli vulvo-perineali per carcinoma squamoso vulvare recidivo.

We report of a case of a fortythree years old women affected by squamous cell cancer of the vulva (T3N0M0). Despite curative treatment (radical vulvectomy with bilateral inguinal and femoral lymphadenectomy), after 41 months she had a local recurrence, retreated with surgery and radiotherapy; another recurrence, after 29 months was treated with chemotherapy, without results. Because of local diffusion with infiltration of the urethra and anus, the patient was submitted to demolitive operation (total pelvic evisceratio, excision of pelvic and perineal soft tissues and reconstruction with rotating skin flaps of the posterior face of the thighs). After two years of follow up, the patient is alive without evidence of disease.

[Concentration of asbestos fibers in urothelial tumors and in the neoplasm-free bladder wall]. / Concentrazione di fibre di asbesto nei tumori uroteliali e nella parete vescicale esente da neoplasia.

The aim of our study was to search the eventual presence of asbestos fibers in the neoplastic tissue of 13 cases of bladder carcinoma and in the normal vesical tissue of 12 control cases without neoplasia and operated upon for other urologic pathologies. To all patients a standardised questionnaire has been administered in order to ascertain the entity of the eventual exposition to asbestos. The organic component of the tissues has been oxidated at low temperature in atomic oxygen plasma and the residual inorganic component has been analysed by transmission electronic microscopy and energy dispersion spectrometry. We have found asbestos fibers only in two over the 25 examined samples; in both cases they belonged to patients affected by the neoplasia and in one of them also by pulmonary asbestos. The procedures that we used in this study, in respect to our other experiences, allowed us to reduce the risk of contamination of the tissues by asbestos, as it is shown by the lower number of cases with positive finding of fibers and by lower concentration of fibers in the positive cases.