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Biomedical subjects

M Pavone-Macaluso

Publications and source records attributed to M Pavone-Macaluso.

At least 37 records · Page 2Linked to original sources
PubMed1996

Genitourinary group phase II study of chemotherapy in stage T3-4 N0-X M0 transitional cell cancer of the bladder: prognostic factor analysis.

The aim of this study was to examine prognostic factors for survival of patients with invasive bladder cancer who had received neoadjuvant chemotherapy followed by further treatment. From 1986 to 1990, 149 eligible patients with T3-4 N0-X M0 bladder cancer were entered into a phase II trial of neoadjuvant chemotherapy, consisting of cisplatin and methotrexate. Patients received two or four courses of chemotherapy, depending on the absence or presence, respectively, of a major clinical response after two courses. 136 patients were evaluable for clinical response after two courses of chemotherapy, and 75 patients were evaluable for pathological response after two or four courses. A multivariate analysis, based on pretreatment variables and the post-treatment variables, clinical response and pathological response, showed that performance status, tumour size and clinical response after two courses of chemotherapy were the only independent prognostic factors for all eligible patients. A second multivariate analysis in the selected subgroup of patients, who underwent a cystectomy, showed that the G-cagetory and pathological response were the only independent prognostic factors. In conclusion, in this group of patients, the response to chemotherapy was a strong and independent prognostic factor in addition to other independent variables. However, it was not accurate or strong enough to allow an impact on the choice of locoregional therapy.

Aged↗
PubMed1996

Results of conservative treatment (transurethral resection plus adjuvant intravesical chemotherapy) in patients with primary T1, G3 transitional cell carcinoma of the bladder.

OBJECTIVES: To evaluate a selected population of 50 consecutive patients with primary T1, G3 bladder transitional cell carcinoma in the absence of carcinoma in situ (Tis) treated with a bladder-sparing approach. METHODS: Between January 1983 and December 1992, all patients were treated by transurethral resection (TUR) plus adjuvant intravesical chemotherapy over 1 year. In most cases, doxorubicin, epirubicin, and mitomycin were used alone or in combination. RESULTS: At a mean follow-up period of 52 months (range, 18 to 126), 16 of 50 patients (32%) showed a recurrent superficial tumor. The recurrent lesion was of Stage T1 in 11 (22%) cases, but was a T1, G3 tumor only in 5 cases (10%). In 2 additional patients (4%) a Tis developed during the observation period after TUR. The mean interval between TUR and first recurrence was 14.6 months (range, 3 to 38). At a mean time of 17 months after the initial TUR, 3 patients (6%) underwent a radical cystectomy due to a progression in T category and 3 additional patients (6%) developed distant metastases at a mean time of 23 months after TUR. In brief, 84% of the patients are alive and tumor-free. Five patients (10%) died of bladder cancer with a mean follow-up of 52 months. CONCLUSIONS: If no concomitant Tis exist, a conservative approach is a legitimate option as an initial treatment of patients with primary T1, G3 bladder tumors.

Administration, Intravesical↗
PubMed1996

Epidemiology, prevention and screening for prostate cancer.

Prostate cancer is a growing social problem. The economical impact is high and is likely to become greater in future years, not only because the number of patients diagnosed with prostatic neoplasias is increasing steadily, but also because of the promotion of screening programmes and the rise in the number of surgical procedures available. It can be concluded that, at the present stage, widespread implementation of screening cannot be recommended. The answer to the question of screening can only be provided by large randomised trials, comparing either screening versus no screening, or early versus delayed treatment in patients in whom early cancer is detected by screening.

Cost-Benefit Analysis↗
PubMed1995

Factors affecting recurrence and progression in superficial bladder tumours.

Prognostic factors in superficial bladder tumours are highly correlated with each other. In this study, their relative importance is examined and grouping of patients in three different prognostic groups suggested. 576 patients (from EORTC protocols 30790 and 30782) were analysed. They have been followed from 3 months to 8.6 years with a median of 4 years. 76 patients developed an invasive tumour (> or = T2); the shortest time to invasion was 12 weeks, the longest was 6.6 years. Time from invasion to death ranged from 3 weeks to 4.4 years with a median of 2 years. Prognostic factors contributing to recurrence, invasion and survival were investigated: age, sex, size of largest tumour, number of tumours, T-category, G-grade, time from diagnosis (years), prior recurrence rate/year, site of involvement. The relative importance of these factors was measured by performing a multivariate analysis based on Cox's proportional hazards regression model. Based on the most important prognostic factors and their association with invasion and death, an index was computed reflecting the risk of both invasion and death due to malignant disease, respectively. The index was used to assign patients to one of three prognostic groups. Three main factors determined patient's prognosis: tumour size, G-grade and prior recurrence rate/year. The model coefficients for invasion were 0.51 (recurrence rate < 1/year, 1-3/year, > 3/year), 84 (grade 1, 2, 3), 0.48 (size < 1.5, 1.5-3, > 3 cm) and for death due to malignant disease 0.89 (recurrence rate), 0.73 (grade) and 0.44 (size), respectively. Risk groups are suggested based on the index. Additional treatment in patients with superficial transitional cell carcinoma of the bladder may be decided depending on the risk group to which the patient belongs.

Adolescent↗
PubMed1995

Is there a role for recombinant tumor necrosis factor alpha in the intravesical treatment of superficial bladder tumors?--a phase II study.

Clinical use of recombinant tumor necrosis factor-alpha is strongly limited by its severe toxicity, mainly cardiovascular, when systemically administered. Recent studies suggest that topical (intrapleural, intraperitoneal, intratumoral) administration is free of significant toxicity. Human recombinant tumor necrosis factor-alpha was administered intravesically, at a dose of 500 mg dissolved in 30 ml of phosphate buffer (pH 7.6-7.8) plus 0.25% human albumin, weekly for two months to 18 patients with papillary transitional cell carcinoma of the bladder. Of the 15 evaluable patients, four (26%) achieved a complete response. Systemic and local tolerability were excellent.

Administration, Intravesical↗
PubMed1994

Androgen receptors and hormone sensitivity of a human prostatic cancer cell line (PC-3) are modulated by natural beta-interferon.

Androgen receptors are expressed at a low level in the cell line PC-3, which does not respond to either androgens or antiandrogens. If these cells are exposed to natural beta-interferon (beta-IFN) a reduction in cell growth and an increase in androgen receptors, evaluated by both biochemical and immunocytochemical techniques, occur. This increase seems not to be related to a selective block of PC-3 in any phase of the cell cycle. Pretreatment with beta-IFN determines in PC-3 cells a partial responsiveness to the androgen dihydrotestosterone as reflected by the increase in cell number. Moreover, the antiandrogen hydroxyflutamide shows agonistic properties by increasing the cell number of PC-3 cells pre-exposed to beta-IFN. When the antiandrogen is tested in combination with interferon, it produces a reduction in the beta-IFN-induced inhibition of cell growth. It is not known whether these unexpected effects are due to the increase in androgen receptors or to other mechanisms.

Androgen Antagonists↗
PubMed1994

Steroid-growth factor interaction in human prostate cancer. 1. Short-term effects of transforming growth factors on growth of human prostate cancer cells.

In order to better define potential mechanisms of growth regulation in human prostate cancer cells, we have compared biological responses (such as short-term response to both transforming growth factor alpha and beta; TFG alpha and TFG beta) in relation to hormone sensitivity of LNCaP, DU145, and PC3 cells. Androgen receptor (AR) and epidermal growth factor receptor (EGF-R) content of each cell line was also investigated. In addition, expression of EGF, TGF alpha, and TGF beta was evaluated through immunofluorescent staining. Growth of androgen non-responsive PC3 cells was stimulated by TGF alpha (about 35%) and inhibited by TGF beta (more than 50%), with respect to controls, after 48 h exposure. Conversely, AR-positive, hormone-responsive LNCaP cells proved to be poorly sensitive, at least short-term, to either growth factor. Furthermore, high levels of both EGF-R and TGF alpha, and a fairly high amount of EGF, were found in DU145 cells and, to a lesser extent, in LNCaP cells; in contrast, PC3 cells exhibited low expression levels of both receptors (EGF-R) and ligands (EGF, TGF alpha), but displayed remarkable TGF beta binding and relatively high levels of endogenous TGF beta. Overall, these results suggest a differential sensitivity to TGF alpha and TGF beta by prostate cancer cells; TGF alpha response seems not to be proportional to the EGF-R content of individual cell lines.

Androgens↗
PubMed1994

Steroid receptors in prostate cancer tissues and cells: pathophysiology, problems in methodology, clinical value and controversial questions.

This paper reviews basic and clinical aspects of human prostate cancer, with special regard to steroid hormones and growth factors, their receptors and the use of these tools in clinical practice. Unlike other endocrine-related tumours, such as breast and endometrial cancer, human prostatic carcinoma has distinctive features that crucially hinder its definition in terms of both biological potential and clinical course. Failure of androgen receptors to represent helpful discriminants for both prognosis and treatment of prostate cancer patients may depend upon methodological pitfalls and/or the heterogeneous composition of most tumour tissues. The former involve either technical problems (tissue sampling and storage, assay procedures) or biochemical and biological points (heterogeneity and functional integrity of steroid binding sites, subcellular and tissue distribution of steroid receptors). The latter mostly concern the unique feature of both normal and diseased prostate gland to present regional diversities in hormone sensitivity and steroid receptor content. Another important area of interest resides in the potential role played by stromal-epithelial interaction in the regulation of growth and function of prostate epithelial cells. In this respect, continued growth of androgen-dependent prostate cancer cells is achieved through intricate pathways where mesenchymal steroid-induced polypeptide growth factors may act in a paracrine/autocrine fashion to mediate androgen action on tumor epithelial cells. In particular, epidermal growth factor (EGF) and transforming growth factor-a (TGFa) may serve as androgen intermediaries in the proliferative control of prostate epithelial cells, but may also be involved in androgen-independent autocrine epithelial cell growth. Clinical correlations of androgen receptors in human prostatic carcinoma have been insofal disappointing. Biochemical or histochemical assays have failed to satisfactorily predict prognosis and response to endocrine therapies of patients. This recalls problems in both methodologies and tissue suitability and points to the need of prolonged follow-up studies wherein special care is placed in sampling conditions, identification of high-affinity sites of steroid binding and selection of threshold values for receptor concentrations. Assay of the EGF receptors might provide additional contribution for a deeper inspection of the biological nature of prostate tumour tissues and help in selecting more appropriate individual-based therapeutic strategies.

Androgens↗
PubMed1993

Correlation between clinical response and urinary interleukin levels using different doses and intravesical administration schedules of interferon-alpha-2b combined with epirubicin: a pilot study.

A total of 62 patients at high risk for recurrence of superficial bladder cancer were selected for a study designed to compare the prophylactic efficacy of different doses and schedules of sequential intravesical instillations of epirubicin and interferon-alpha-2b and to evaluate which sequence could enhance the release of cytokines in the urine. Our investigations showed a significant increase in urinary concentrations of interleukins in patients who received the sequential intravesical administration of epirubicin and interferon-alpha-2b. Higher urinary concentrations of interleukins and a lower recurrence rate were detected in patients who received interferon-alpha-2b 24h after epirubicin instillation.

Administration, Intravesical↗
PubMed1993

Intravesical mitoxantrone in superficial bladder tumours (Ta-T1).

36 patients with histologically proven grade G1-G2, Ta-T1 transitional cell carcinoma of the bladder were introduced, after transurethral resection (TUR), into a study of intravesical chemoprophylaxis with mitoxantrone (20 mg diluted in 50 ml). After a mean follow-up of 23 months, 16 (50%) patients showed a superficial recurrence with a mean recurrence rate of 0.56 per year. In 19 patients with recurring tumours the mean recurrence rate decreased from 1.65 to 0.58 per year. 9 patients (25.7%) suffered from a chemical cystitis that in 2 cases (5.7%) required treatment interruption.

Administration, Intravesical↗
PubMed1993

Current views on intravesical treatment and chemoprophylaxis of superficial bladder cancer. The present role of epirubicin and doxorubicin.

Since 1972, a large number of studies have shown that intravesical treatment with doxorubicin (adriamycin) is effective against carcinoma in situ and multiple papillary tumors. Furthermore, it significantly reduces the recurrence rate after transurethral resection. Its efficacy has been compared with that of Bacillus Calmette-Guerin (BCG), which is the only treatment accepted by the US Food and Drug Administration for therapy of carcinoma in situ (Tis). In more recent years, a few studies have been performed using intravesical epirubicin in the hope that different properties of the molecule might enhance the activity of the anthracyclines, but produce fewer and milder side-effects. After weekly instillations of epirubicin (50 mg in 50 ml of sterile water) a complete response is achieved in 47% of patients with a histologically proven papillary marker lesion. The prophylactic efficacy of even a single instillation of epirubicin within 6 hours after transurethral resection (TUR) was proved in a randomized study (30863) of the EORTC (European Organization for Research on Therapy of Cancer) Urological Group. A randomized Italian trial (Blinst 4) of chemoprophylaxis after TUR investigated the efficacy of different intravesical administration schedules of epirubicin (50 mg in 50 ml of sterile water). All treatment regimens were more effective than no treatment. The sequential intravesical combination of epirubicin and interferon-alpha-2b has shown, in our personal experience, encouraging clinical results and our laboratory data suggest the synergic activation of the local immune response.

Administration, Intravesical↗
PubMed1992

Soluble and nuclear type I and II androgen-binding sites in benign hyperplasia and cancer of the human prostate.

This paper presents an approach for the assessment of the androgen receptor (AR) status in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) tissues. Evaluation of AR was carried out in both soluble and nuclear fractions by a standard competition method, using tritiated mibolerone as radioligand. Based on our experience with breast and endometrial cancer, this approach focused on both type I (high affinity, low capacity) and type II (reduced affinity, higher capacity) binding sites, aiming mainly at establishing a putative "functional" receptor mechanism, i.e., the presence of type I AR in both cytosol and nucleus. Ancillary studies were carried out to exclude a potential overestimation of the AR content by interference with other steroid receptors, namely, progesterone (PgR) or glucocorticoid (GcR) receptors. Results showed that the interaction by PgR or GcR upon AR measurement was not relevant. The distribution of AR, namely the percent of positivity either in a single or in both cell compartments, was not significantly different in BPH (N = 32) or PCa (N = 24) tissues. For type I binding, the percent of positivity in both soluble and nuclear fractions (i.e., the "functional" AR status) was very close to that observed for other endocrine-related tumors, like breast cancer. Concentrations of type I AR appeared significantly higher in PCa than in BPH tissues; this was true for both soluble and nuclear fractions. In contrast, no significant difference was found in type II AR concentrations in either cell fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

The flexible cystoscope.

We have been using the flexible cystoscope since 1987. Detailed information is given concerning the technique of flexible cystoscopy, its indications, advantages and disadvantages. A comparison is made with the results obtained using the rigid cystoscope in an initial series of 100 patients, yielding false negative results in only 8% of cases during the learning period. The flexible scope can be successfully employed for Neodymium YAG laser coagulation of superficial bladder tumours. The conclusion is reached that once the urologist has learned how to use it, he will consider the flexible cystoscope as a fundamental tool in his diagnostic armamentarium and false negative results will decrease almost to zero, especially if additional investigations, namely cytology, are routinely adopted.

Cystoscopes↗
PubMed1992

A European Organization for Research and Treatment of Cancer--Genitourinary Group phase 2 study of chemotherapy in stage T3-4N0-XM0 transitional cell cancer of the bladder: evaluation of clinical response.

From 1986 to 1990 the European Organization for Research and Treatment of Cancer--Genitourinary Group conducted a phase 2 trial of neoadjuvant chemotherapy in patients with stage T3-4N0-XM0 transitional cell carcinoma of the bladder. The objectives were to evaluate the clinical response in relation to the pathological response, and to measure the side effects of chemotherapy. Of 171 patients entered 136 were fully evaluable: 18% had clinical complete remissions, 36% had clinical partial remissions, 39% had no clinical remissions and 10% had unknown response. A selected subgroup of 76 patients underwent cystectomy after 2 or 4 courses of chemotherapy: 2 were not evaluable for pathological response because of preoperative radiotherapy after neoadjuvant chemotherapy, 16 had a pathological complete remission, 7 had a pathological partial remission and 51 had no pathological remission. Comparison of the clinical response or T category only after 2 courses of chemotherapy with the pathological response after 2 or 4 courses of chemotherapy showed that in a number of patients the disease status could be downstaged to pathological complete or partial remission by additional courses of chemotherapy. If the discrepancies between clinical and pathological responses, or between T and P categories, induced by further downstaging after additional chemotherapy were left out, it was shown that clinical complete and partial remissions were a heterogeneous group but nonresponders could be delineated with a 100% accuracy by clinical response evaluation and transurethral resection biopsy only. Furthermore it seems important to establish the number of chemotherapy courses to induce a maximal response of the primary tumor.

Adult↗
PubMed1992

A pilot study comparing different dose levels and administration schedules of interferon-alpha 2b combined with epirubicin for prevention of recurrence in bladder cancer.

A pilot study in 62 patients has been carried out to evaluate the combination of epirubicin and interferon (IFN)-alpha 2b using different doses and schedules of intravesical administration in the prevention of recurrence of bladder cancer. Preliminary results show greater prophylactic efficacy not only when higher doses of epirubicin and IFN-alpha 2b are used but also when a larger interval between instillation of the compounds was used.

Administration, Intravesical↗
PubMed1992

Intravesical therapy of superficial bladder transitional cell carcinoma with tumor necrosis factor-alpha: preliminary report of a phase I-II study.

A phase I-II trial of intravesical immunotherapy with tumor necrosis factor (TNF)-alpha in 24 patients affected by superficial bladder tumors is herein presented. Of these, 11 patients were submitted, at weekly intervals, after complete TUR, to 8 instillations of TNF-alpha at increasing doses from 50 to 600 micrograms. Tolerability was excellent, even at the highest dose. In a second group of 13 patients with a histologically proved papillary marker lesion, TNF-alpha was instilled at weekly intervals at the dose of 500 micrograms for 8 weeks. Three complete responses (23%) were obtained.

Administration, Intravesical↗