Open-label randomised phase III trial of vinflunine versus an alkylating agent in patients with heavily pretreated metastatic breast cancer.

Background: There is no standard treatment after progression on second-line chemotherapy for metastatic breast cancer (MBC). We compared vinflunine with physician's choice of alkylating agent (AA) for patients with heavily pretreated MBC. Patients and methods: In this open-label phase III trial, patients with MBC were included if they had received at least two prior chemotherapy regimens for MBC and had received anthracycline, taxane, antimetabolite and vinca alkaloid therapy. Patients were no longer candidates for these chemotherapies because of resistance and/or intolerance. Patients were randomised to either vinflunine 280 mg/m2 intravenously every 3 weeks (q3w) or AA monotherapy q3w. Stratification factors were performance status, number of prior chemotherapy lines for MBC, disease measurability and study site. The primary end point was overall survival (OS). Results: A total of 594 patients were randomised (298 to vinflunine, 296 to AA). There was no difference between treatment arms in OS (hazard ratio 1.04, P = 0.67; median 9.1 months for vinflunine versus 9.3 months for AA), progression-free survival (hazard ratio 0.94, P = 0.49; median 2.5 versus 1.9 months, respectively) or overall response rate (6% versus 4%, respectively). However, the disease control rate was significantly higher with vinflunine than AA (44% versus 35%, respectively; P = 0.04). The most common adverse events (any grade) were haematological and gastrointestinal disorders and asthenia in both arms. The most common grade 3/4 adverse events were neutropenia (19% versus 11% with vinflunine versus AA, respectively) and asthenia (10% versus 4%). Conclusions: Vinflunine 280 mg/m2 q3w did not improve OS compared with the physician's choice of AA as third- or later-line therapy for MBC. Vinflunine demonstrated an acceptable safety profile, suggesting that vinflunine 320 mg/m2 merits evaluation. ClinicalTrials.gov: NCT01091168.

High cardiovascular risk in Spanish workers.

BACKGROUND AND AIMS: To investigate the prevalence of high cardiovascular risk in the Spanish working population, and its distribution among different occupations and gender. METHODS AND RESULTS: Cross-sectional study of 309,955 workers (72.6% males, mean age 36.5 years, range 16-74 years), who underwent a routine medical check-up. Workers were classified as high, intermediate or low cardiovascular risk, according to the SCORE system. Workers with a relative risk greater than 4 were also considered as high-risk. The prevalence of high cardiovascular risk was 7.6% (95% CI 7.5-7.7) in males and 1.7% (95% CI 1.6-1.8) in females. After adjusting for age and gender, the prevalence of high cardiovascular risk was greater in workers from the Agriculture and Construction sectors than in those from Industry and Service sectors. The prevalence of high cardiovascular risk was higher in blue-collar than in white-collar occupations. CONCLUSIONS: A sizeable proportion of workers, especially blue-collar males, are at high cardiovascular risk. Knowledge of this risk for certain workers may serve as a basis for preventive strategies.

Cephapirin-induced neutropenia.

Five cases (3.5%) of reversible cephapirin-induced neutropenia were observed in 132 patients receiving this antibiotic. The disorder was severe (agranulocytosis) in 3 cases. Simultaneous maculopapular rash was observed in all of them and in 4 cases fever occurred. All the cases observed were female (p not significant). Neutropenia developed only after administration of high doses of the antibiotic for a prolonged period of time. In contrast to another 127 patients treated with cephapirin who did not develop neutropenia, neutropenic patients had received a mean daily dose, total dose, mean daily dose per kilogram and total dose per kilogram of body weight significantly larger (p = 0.05, 0.02, 0.001 and 0.001, respectively). The duration of therapy was significantly longer in the neutropenic group (p = 0.001). Neutropenia did not occur below 90 g of total dose, but when this amount was exceeded, the incidence of the disorder reached 26.3% (p less than 0.001). We conclude that when this drug must be used either for long periods of time or at high doses, a hematologic vigilance is recommendable.