Multimodal treatment of locally advanced transitional cell bladder carcinoma in elderly patients.

22 patients with locally advanced (T3-T4, M0) transitional cell bladder carcinoma, age greater than 70 years, with medical contraindication or refusal of radical cystectomy, were treated following an ample transurethral resection (TUR), with three chemotherapy cycles. Each cycle consisted of 5-fluorouracil 500 mg/m2 intravenously (i.v.) on days 1 and 8, epirubicin 60 mg/m2 i.v. on day 1 and cisplatin 50 mg/m2 i.v. on day 1. Cycles were repeated every 3 weeks. Subsequently, patients were submitted to a repeat TUR on the area of the initial neoplasm. At computed tomography (CT) scan evaluation, response rate to chemotherapy was 54.5%, with two complete responses. No residual disease (R0) at postchemotherapy TUR was encountered in 8 cases (36%), and microscopic disease (R1) in 4 cases (18%). Median duration of complete responses (R0) was 13.5 months (range 7-57+). Radiation therapy was carried out in 12/14 patients with residual disease at repeat TUR. Overall median duration of response was 10.2 months, while overall actuarial median survival was 11.6 months. Four-year survival was 29%. The approach described was feasible. The chemotherapy regimen employed was not as active as current regimens used in younger patients. The search for more active regimens which are tolerable by the elderly is important.

Mitomycin C treatment of advanced, hormone-resistant prostatic carcinoma: a phase II study.

From February 1984 to February 1987, 29 patients with advanced, hormone-resistant prostatic carcinoma were treated with mitomycin-C at a dose of 20 mg/m2 every 6 weeks (15 mg/m2 in patients greater than 75 years old and in those who had undergone previous radiotherapy). In the 27 evaluable patients, there were no complete remissions (CR), 2 partial remissions (PR), 14 stabilizations (STAB), and 11 cases of progressive disease (PRO). Ten stabilized patients showed significant pain reduction. Toxicity was minimal. The actuarial median survival was 10.8 months. In this study, mitomycin C was not active in terms of CR + PR; however, a beneficial symptomatic effect was frequently observed.

Pattern and determinants of diagnostic interval in cancers of the prostate, bladder and kidney.

The present study examined the pattern of presentation and diagnostic interval, i.e. number of months between first cancer symptom or sign and first medical visit, in 444 cases of urological cancer (122 of prostate cancer, 187 of bladder cancer and 135 of kidney cancer). The mean diagnostic interval was 7.6 months for prostate, 5.6 for bladder and 4.5 kidney cancer. A chance diagnosis, i.e. in absence of any symptom or sign, was reported by 16%, 8% and 18% of patients with cancer of the prostate, bladder and kidney respectively. We observed on significant differences in diagnostic intervals according to patients' demographic, sociocultural, and life-style characteristics, or tumor stage. Better quantitative and qualitative data on the pattern and determinants of delay in cancer diagnosis are clearly warranted, and the present study, although largely negative, shows the possibility of using large-scale epidemiological investigations for this purpose.

Proliferative activity in human urologic malignancies: a preliminary study.

Cellular proliferative activity was evaluated by the determination of 3H-thymidine labeling index (LI) in 20 specimens of human urologic malignancies (13 renal cell carcinomas and 7 transitional cell bladder carcinomas). Very low LI values were found in renal cell carcinomas, with a median value of 0.28%. Slightly higher proliferative activities were observed in bladder carcinomas, with a median LI value of 1.96%. No significant correlations were found between proliferative activity and pathologic stage or histologic grading in renal cell carcinomas. Although the number of bladder carcinomas evaluated does not allow any definite conclusion, an increase in LI values was found from in situ to invasive carcinoma and from tumors at stage I to tumors at stage III.

[Evaluation of the specific delayed cutaneous hypersensitivity response(DTCH) after specific active immunotherapy (SAI) using autologous tumor cells in patients operated upon for renal carcinoma]. / Valutazione della risposta cutanea di ipersensibilità ritardata specifica (DTCH) dopo immunoterapa attiva specifica (ASI) con cellule tumorali autologhe in pazienti operati di carcinoma renale.

From Dec 1986 to Dec 1990, 113 consecutive patients radically resected for renal cell carcinoma, have been randomized after surgery to observation or to Active Specific Immunotherapy (A.S.I.). 43 patients stage I-II and 13 p. stage III, according to TNM entered the treatment arm consisting of 10 autologous irradiated tumor cells injected intradermally, either mixed with BCG 10(7) (on days 28th and 35th after surgery) or alone (on day 42th). At randomization and 1, 6 and 12 months after treatment, patients were evaluated for the development of a DTCH to autologous tumor and to autologous normal cells, obtained by mechanical and enzymatic dissociation of the surgical specimens. Baseline DTCH were negative in all patients. One month after completing A.S.I. 36 out of 50 evaluable patients displayed a significant DTCH response to autologous tumor, which remained positive in 23/40 patients at 6 months. Our data clearly indicate that Active Specific Immunotherapy with autologous tumor cells mixed with BCG can elicit a specific immune response to autochthonous tumor as measured by DTCH.

Developing central nervous system and vulnerability to platinum compounds.

Comparative studies on the effects of the platinum complexes in use or in clinical trials are carried out in order to discover differences in the neurotoxic potential and the reversibility of neurotoxicity. In this paper, we summarized the current literature on neurotoxicity and chemoresistance of cisplatin (cisPt) and discussed our recent efforts on the interference of cisPt and a new platinum compound [Pt(O,O'-acac)(γ-acac)(DMS)] (PtAcacDMS), with high specific reactivity with sulphur ligands instead of nucleobases as cisPt, on some crucial events of rat postnatal cerebellum development. The acute effects of drug treatments on cell proliferation and death in the external granular layer and granule cell migration and the late effects on the dendrite growth of Purkinje cells were evaluated. Together with the demonstrated antineoplastic effectiveness in vitro, compared with cisPt, data suggest a lower neurotoxicity of PtAcacDMS, in spite of its presence in the brain that involves considerations on the blood brain barrier permeability.

Extrapulmonary small cell carcinoma: a single-institution experience and review of the literature.

BACKGROUND: Small cell carcinoma (SCC) is a distinct pathologic entity that may also occur in extrapulmonary sites. In this report the retrospective results of multimodal therapy of primitive extrapulmonary (E) SCC, in a single institution series, are presented. METHODS: Twenty-four patients (pts) with ESCC were referred to the Centro di Riferimento Oncologico, Aviano, Italy, from 1986 to 1992. Clinico-therapeutic findings were evaluated in 20 pts. Their ages ranged from 20 to 87, with a median of 60.5 years. Primary tumor sites were urinary bladder (5 pts), prostate (4 pts), larynx (3 pts), kidney (2 pts), ovary, skin, oropharynx, trachea, uterine cervix, ethmoid, and stomach (1 pt each); lymph node metastases of unknown origin were observed in 3 pts. More than 50% of pts presented extensive disease. RESULTS: Histologically, 16 cases were pure ESCCs and 8 cases were combined, 4 of them with adenocarcinoma, 2 with transitional cell carcinoma, and 2 with squamous cell carcinoma. Immunohistochemical studies, performed in 7 cases, demonstrated the epithelial nature of these tumors. The cisplatin-VP16 (PE) regimen was used in 13 pts, and 9 of them (69%) obtained objective responses after chemotherapy (CT) alone, with 3 complete remissions (CR) and 6 partial remissions (PR). Median CR and PR duration was 13+ and 24 months, respectively. Radiotherapy was performed in 7/13 pts after induction CT and before consolidation CT. The objective response rate was 100%, with 6 CR and 1 PR. No severe toxic side effects and no toxic deaths were reported. A patient treated with surgery alone for a urinary bladder tumor showed continuous long-term survival, while 1 of 2 pts treated with radiotherapy alone obtained PR. CONCLUSIONS: The PE regimen has an activity similar to the one observed in pulmonary SCC.

Combination chemotherapy with fluorouracil, adriamycin, cis-platinum and VM-26 in advanced transitional cell carcinoma of the urinary tract.

From October 1981 to October 1984, 42 consecutive patients with locally advanced unresectable or metastatic transitional cell carcinoma of the urinary tract were treated with cis-Platinum 50 mg/m2 i.v. and Adriamycin 50 mg/m2 i.v. day 1, and Fluorouracil 500 mg/m2 i.v. and VM26 100 mg/m2 days 1 and 8, every 3 weeks. In the 36 evaluable patients, 4 complete remissions and 15 partial remissions were noted (52.7% response rate). Of the 12 patients with previously untreated, locally advanced bladder carcinoma, 8 responded, with 3 pathologically confirmed complete remissions. Toxicity was moderate. Median survival was 44 weeks. This 4-drug combination had significant palliative activity in our patient population. Its role in the preoperative setting deserves further evaluation.

Buserelin treatment of advanced prostatic carcinoma: prognostic factor analysis.

From August 1986 to August 1990, 116 patients with prostatic carcinoma, advanced disease (stage C-D1 only in patients older than 75 years, or D2) were treated with Buserelin (0.5 mg 3 times/day subcutaneously for 7 days, followed by 0.4 mg 3 times/day intranasally) until progression. No concomitant antiandrogens were administered. Of the 108 evaluable patients, 10 had complete remission (CR), 49 partial remission (PR), 46 remained stable while 3 progressed (response rate = 54.6%). Median duration of response was 31 months, median survival was 34 months. The toxicity of treatment was mild and mainly related to the hormonal effect of the drug. Castrate testosterone levels were obtained in all patients except 7. Slight, transient pain increase was noted at day 8 in 12 patients. Absence of symptoms at the start of treatment, well- or moderately differentiated tumor and serum testosterone negativization following Buserelin were associated with a significantly higher response rate as compared to presence of symptoms, poorly differentiated tumor and failure to obtain castrate testosterone levels, respectively. The following prognostic factors were found, at univariate analysis, to be associated with a prolonged survival: stage (C-D1 versus D2), PS (greater than 80 versus equal or less than 80), symptoms (absent versus present) and histological grade (G1 + G2 versus G3). Age and basal T levels did not influence survival. Those patients who obtained a CR or PR survived significantly longer than those with stable disease or progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Buserelin treatment of advanced prostatic cancer: a phase II study.

From August 1986 to September 1988, 76 eligible patients with advanced prostatic carcinoma, measurable or evaluable disease, no previous hormonal treatment, were treated with Buserelin at a dosage of 500 micrograms every 8 h for 7 days, followed by 400 micrograms intranasally three times a day. No concomitant antiandrogens were administered. In the 63 evaluable patients (11 patients not yet evaluable because of short treatment time, two lost to follow-up), three complete remissions, 28 partial remissions, 30 stable disease and two progressions were obtained (National Prostatic Cancer Project criteria). Median duration of response was 55+ weeks. Side effects were modest, mostly related to the endocrinological effects of Buserelin. Transient increase in serum testosterone levels was found in 37% of the evaluable patients, but transitory 'flare-up' was present in seven patients only. With a median follow-up time of 11.5 months, median survival has not been reached. In conclusion, this study confirmed the activity of Buserelin and the feasibility of its middle-term administration.

Presurgery chemotherapy (CT) in locally advanced bladder carcinoma: a feasible and possibly effective approach.

In October 1984, a prospective pilot study aiming to evaluate the feasibility and to preliminarily test the efficacy of the chemotherapy--surgery sequence in locally advanced bladder carcinoma was started at our institutions. Chemotherapy consisted of adriamycin 50 mg mq-2 and cisplatin 50 mg mq-2 on day 1 and fluorouracil 500 mg mq-2 and teniposide 100 mg mq-2 on days 1 and 8; chemotherapy was repeated every 3 weeks for three cycles and followed by surgery (radical cystectomy; TUR if radical surgery medically contraindicated). The characteristics of the 28 patients so far treated include: T3b in 26 patients, local relapse after surgery in two, nodal metastases in seven. Twenty-five patients were male and three female, median age was 61 yr (range 42-75). Clinical response following chemotherapy was: complete remission (CR) in five patients, partial remission (PR) in 15, stable disease (SD) in three, progression (PRO) in two. Three patients are not evaluable. Treatment was moderately well tolerated. Thirteen patients underwent radical surgery, three exploratory surgery, three TUR; refusal in three patients, early death in two, too early in one. No evidence of disease was found in the surgical specimen of five patients (three CR, two PR), microscopic residual disease in four PR patients, gross residual disease in 11 patients (one CR, six PR, two SD, two PRO). Actuarial median survival (all 28 patients) is 45% at 36 months. These preliminary results suggest that the combination of chemotherapy and surgery is feasible and may be effective in these poor prognosis patients.