Thrombosis-related complications and mortality in cancer patients with central venous devices: an observational study on the effect of antithrombotic prophylaxis.

BACKGROUND: Recent guidelines do not recommend antithrombotic prophylaxis (AP) to prevent catheter-related thrombosis in cancer patients with a central line. PATIENTS AND METHODS: This study assessed the management of central lines in cancer patients, current attitude towards AP, catheter-related and systemic venous thromboses, and survival. RESULTS: Of 1410 patients enrolled, 1390 were seen at least once in the 6-month median follow-up. Continuous AP, mainly low-dose warfarin, was given to 451 (32.4%); they were older, with a more frequent history of venous thromboembolism (VTE), and more advanced cancer. There was no difference in catheter-related thrombosis in patients given AP or not (2.8% and 2.2%, odds ratio 1.29, 95% confidence interval 0.64-2.6). The median time to first catheter-related complication was 120 days. Systemic VTE including deep and superficial thromboses and pulmonary embolism, were less frequent with AP (4% versus 8.2%, P = 0.005). Mortality was also lower (25% versus 44%, P = 0.0001). Multiple logistic regression analysis found only advanced cancer and no AP significantly associated with mortality. No major bleeding was recorded with AP. CONCLUSIONS: Current AP schedules do not appear to prevent catheter-related thrombosis. Systemic VTE and mortality, however, appeared lower after prophylaxis.

Cisplatin-vinorelbine combination chemotherapy in locally advanced non-small cell lung cancer.

AIM: The North Milan Group presents the results of a phase II study on a cisplatin-vinorelbine combination schedule in the treatment of locally advanced non-small cell lung cancer to evaluate its activity and tolerability. METHODS: Seventy-six consecutive patients entered the study. Patients' characteristics were the following: males/females 69/7; median age, 61.4 years (range, 40-73); ECOG performance status, 0-1; 17 stage IIIa and 59 stage IIIb. There were 49 squamous cell carcinomas, 20 adenocarcinomas, and 7 large cell carcinomas. All patients had not been previously treated and showed measureable disease. Treatment consisted of vinorelbine, 25 mg/m2 on days 1 and 8, plus cisplatin, 80 mg/m2 on day 1, administered intravenously every 21 days for three standard courses. RESULTS: Seventy-four patients were evaluable for response. Objective responses were documented in 42/74 patients with an overall response rate (CR+PR) of 56.7%; 18/74 patients (24.3%) showed stable disease and the remaining 14/74 (18.9%) went into progression. Twelve patients (16.2%) were suitable for a subsequent surgery. The median duration of response was 13.3 months. Survival time ranged from 4 to 36 months; it was 14.6 months for PR patients, 8.6 months for NC and 5 months for PD. Mean survival time is presently 12.85 months (SE, 1.2 months). Toxicity evaluated on 222 cycles administered was acceptable, and it was necessary to use G-CSF or delay the treatment because of severe leukopenia in only a few cases. CONCLUSIONS: The regimen is active and safe: the slight survival increase is likely due to the small amenability to surgery achieved (16.2%). However, our results are fully comparable to others obtained with vinorelbine in two/three drug combination chemotherapy regimens.

Levodropropizine (LD) activity in allergic asthmatic patients, challenged with ultrasonically nebulized distilled water, metacholine and allergen-induced bronchospasm.

The antitussive compound Levodropropizine (LD) is active in animal bronchoconstriction induced by histamine and capsaicin and in man protects from bronchoconstriction induced by capsaicin. The primary objective of this study was to evaluate the mechanism of action of LD given at 60 mg t.i.d. as oral drops, for 8 days by means of specific bronchial challenges (allergens) and of aspecific challenges acting via different receptors and fibers (i.e. metacholine via cholinergic receptors and ultrasonically nebulized distilled water (UNDW) via histamine and neuropeptide release). The study design is randomized, double-blind, cross-over versus placebo in 30 allergic asthmatic patients. Baseline bronchial tone and bronchoconstrictor response to metacholine (MCh) were not modified by active treatment nor by placebo. On the contrary, in airway responsiveness to UNDW, the active treatment showed an antagonist effect against induced bronchoconstriction of 59% [activity ratio (AR) as antilog = 0.41; 95% confidence interval 0.35-0.54; p < or = 0.05] in comparison to no effect for placebo. Similarly, in airway responsiveness to specific allergen, active treatment antagonized the bronchoconstrictor effect of grass pollen by 83% and of various allergens (dermatophagoides and grass pollen) by 72%, i.e. AR of 0.17 (95% confidence interval 0.045-0.65; p < 0.01) and of 0.28 (95% confidence interval 0.07-1.04; p < 0.05), respectively. No antagonist effect was evident with placebo at all times. Besides inhibiting cough, LD is also partially effective in inhibiting bronchial hyperreactive response against specific allergen and UNDW bronchoconstriction. Hence, LD might act by partly inhibiting histamine and neuropeptide release.

Cisplatin plus epirubicin and etoposide followed by irradiation plus lonidamine in stage III nonsmall cell lung cancer.

Forty-seven patients with stage III nonsmall cell lung cancer (NSCLC) were treated with the sequential administration of combination chemotherapy consisting of cisplatin, epirubicin and etoposide and of irradiation plus lonidamine. The response rate was 49% after chemotherapy with an improvement of 14% after radiation therapy and lonidamine. The median survival was around 15 months for responders and 9 months for nonresponders. Toxicity was moderate and acceptable. It is concluded that this schedule is active in the treatment of NSCLC.

Six-drug sequential chemotherapy in non small cell lung cancer. A North Milan Group Study.

Forty-five patients with inoperable non small cell lung carcinoma were treated according to a sequential polychemotherapeutic regimen with cisplatin-vinblastine (A), cyclophosphamide-etoposide (B), and adriamycin-vincristine (C). Patients were evaluated every two cycles. Ten patients (22.2%) showed a partial response with a mean duration of 20 weeks, and mean survival of 50.8 weeks. It is remarkable that, among them, 6 patients (13.3%) lived over 12 months and three (6.6%) over 18 months. The mean survival for all patients was 35.7 weeks. Toxicity was acceptable and reversible.

Transient blindness and seizure associated with cisplatin therapy.

A 38-year-old woman with adenocarcinoma of unknown origin was treated with cisplatin and etoposide. After the 4th course of chemotherapy she complained of blindness and had a seizure with spontaneous recovery in 4 days. The relationship between these events and the known neurotoxicity of other heavy metals indicate cisplatin as a possible etiologic factor.