Lung cancer risk in Venice: a population-based case-control study.

Populations resident in the historical town of Venice and in the inland industrial city of Mestre are at different risk of exposure to environmental pollutants. This case-control study compares the risk of developing lung cancer in the two populations in relation to known risk factors for this neoplasm. A retrospective study of 305 incident cases of lung and 447 frequency-matched population controls was conducted through a standard questionnaire on main risk factors for lung cancer. Completeness of cases was checked against the Venetian Cancer Registry files. The results indicate that lung cancer risk associated with tobacco smoking was high in both areas, although more elevated in Venice islands among heavy smokers. An elevation of risk was associated with housing without a heating system, possibly suggesting a role of worse hygienic conditions. An increased risk associated with exposure to occupational carcinogens was detected in the inland area. In conclusion, lung cancer risk due to tobacco smoking largely affects both the populations, while other risks such as occupation or housing conditions appear to be more population-specific.

Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: a study by the Gruppo di Studio sui Tumori della Testa e del Collo.

BACKGROUND: The standard treatment for advanced (stage III and IV) head and neck squamous cell carcinoma (i.e., surgery with postoperative radiotherapy in operable patients and radiotherapy alone in inoperable patients) has had poor results. A series of randomized trials of induction chemotherapy have up to now failed to demonstrate an improvement in survival. PURPOSE: This trial was designed to determine whether intensive induction chemotherapy administered before loco-regional treatment would improve survival of patients with advanced disease. METHODS: Patients had previously untreated, advanced nonmetastatic (stages III and IV) squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and paranasal sinuses. The study design was a randomized, multi-institutional, phase III trial. Eligible patients (n = 237) were randomly assigned to receive either initial chemotherapy (cisplatin and infusional fluorouracil) followed by loco-regional treatment (group A, n = 118) or loco-regional treatment alone (group B, n = 119). For operable patients (group A, n = 34; group B, n = 32), loco-regional treatment included resection followed by adjuvant radiotherapy. For inoperable patients, radical irradiation was performed with a planned dose of 65-70 Gy to involved areas. A dose of 45-50 Gy was also planned to the uninvolved neck or postoperatively. The statistical (log-rank) test was performed no earlier than 2 years after the randomization of the last patient. RESULTS: Seventy-one patients (60%) in group A and 67 patients (56%) in group B were considered free of disease after they completed the treatment sequence. The analysis of time to distant metastases showed an advantage for group A patients. (Respective 2- and 3-year values for inoperable patients were 15% and 24% for group A versus 36% and 42% for group B, P = .04; only one operable group A patient had distant metastases after 49 months versus 26% [2 years] and 31% [3 years] for operable group B patients, P = .01.) For inoperable patients, the combined treatment was significantly associated with an increase in complete remission rate (group A, 44%) as compared with radiotherapy alone (group B, 30%) (P = .037). Inoperable patients also benefitted from induction chemotherapy in terms of disease-free survival (49% and 34% for group A versus 28% and 26% for group B; P = .06) and of overall survival (30% and 24% for group A versus 19% and 10% for group B; P = .04). CONCLUSIONS: When all 237 randomly assigned patients were analyzed, there were no significant differences in the two treatment strategies in loco-regional failure or in disease-free or overall survival, although the development of distant metastases was reduced. For operable patients, the only benefit from neoadjuvant chemotherapy was a significant reduction in the incidence of distant metastases. For inoperable patients, neoadjuvant chemotherapy improved local control, decreased the incidence of distant metastases, and improved the complete remission rate and overall survival. IMPLICATIONS: Confirmatory studies with effective chemotherapy regimens delivered for an adequate number of cycles are required.

Propionyl-L-carnitine: a new compound in the metabolic approach to the treatment of effort angina.

The effects of propionyl-L-carnitine on exercise tolerance of 12 patients with stable exertional angina were assessed in a double-blind, placebo-controlled, cross-over protocol using serial exercise tests. Compared to placebo, propionyl-L-carnitine significantly increased total work from 514 +/- 199 to 600 +/- 209 W (P less than 0.05) (17%) and prolonged exercise time and time to ischemic threshold from 515 +/- 115 to 565 +/- 109 sec (P less than 0.05) (10%) and from 375 +/- 102 to 427 +/- 93 sec (P less than 0.01) (14%), respectively. ST segment depression at the highest common work level was significantly reduced from 0.19 +/- 0.08 to 0.15 +/- 0.08 mV (P less than 0.05) (21%). No significant changes in heart rate, systolic blood pressure, and rate-pressure product at rest, at the highest common work level, on appearance of the ischemic threshold, or at peak exercise were observed after propionyl-L-carnitine treatment. No side effects were observed under propionyl-L-carnitine treatment. This study shows that propionyl-L-carnitine can significantly improve exercise tolerance in patients with stable angina. Our data seem to confirm that propionyl-L-carnitine most likely exerts its protective action via the metabolic pathway.

Efficacy and duration of the effect of gallopamil sustained release in patients with chronic stable effort angina.

This double-blind, placebo-controlled, cross-over study was designed to evaluate the effects and duration of action of gallopamil sustained release (SR) in patients with stable effort angina. Exercise tests were performed 3, 8, and 12 hours after the last administration of placebo or gallopamil SR. Blood samples for plasma gallopamil concentration were taken just before each exercise test. Statistical analysis was performed using an analysis of variance for multiple comparisons with evaluation of interaction between sequence and period according to a cross-over design. Compared to placebo, gallopamil SR significantly prolonged exercise time from 412 +/- 100 to 481 +/- 71 s (p less than 0.02; 17%), from 416 +/- 88 to 484 +/- 67 s (p less than 0.01; 16%), and from 364 +/- 88 to 440 +/- 85 s (p less than 0.02; 21%) at 3, 8 and 12 hours respectively after administration. Time to -1 mm ST segment depression was also significantly prolonged from 263 +/- 56 to 336 +/- 76 s (p less than 0.001; 28%), from 262 +/- 81 to 356 +/- 70 s (p less than 0.001; 36%), from 231 +/- 65 to 291 +/- 76 s (p less than 0.001; 26%), respectively. No significant relationship between plasma levels and anti-ischemic activity was observed. In conclusion, our data show that gallopamil slow-release is effective in improving exercise tolerance of patients with chronic angina and that its therapeutic effect persists, substantially unchanged, up to 12 hours after administration.

Phase III randomized study of fluorouracil, epirubicin, and cyclophosphamide v fluorouracil, doxorubicin, and cyclophosphamide in advanced breast cancer: an Italian multicentre trial.

From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.