Randomized phase II study comparing efficacy and safety of combination-therapy trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed by docetaxel alone at progression as first-line chemotherapy in patients with HER2+ metastatic breast cancer: HERTAX trial.

BACKGROUND: Because chemotherapy for metastatic breast cancer (MBC) is associated with relevant toxicity, sequential monotherapy trastuzumab followed by cytotoxic therapy at disease progression might be an attractive approach. METHODS: In a multicenter phase II trial, 101 patients with overexpression of human epidermal growth factor receptor 2 (HER2(+)) MBC were randomized between combination-therapy trastuzumab (Herceptin) plus docetaxel (H+D) and sequential therapy of single-agent trastuzumab followed at disease progression by docetaxel alone (H→D) as first-line chemotherapy for metastatic disease. The primary endpoint was progression-free survival (PFS) after completed sequential or combination therapy. RESULTS: For the H+D group the median PFS was 9.4 vs. 9.9 months for the H→D group and 1-year PFS rates were 44% vs. 35%, respectively. However the overall response rates (ORRs) were 79% vs. 53%, respectively (P = .016), and overall survival was 30.5 vs. 19.7 months, respectively (P = .11). In the H→D group, response rates to monotherapy trastuzumab and subsequent docetaxel were 34% and 39%, respectively, with a median PFS during single-agent trastuzumab of 3.9 months. The incidence and severity of neuropathy were significantly higher in the H+D group. Retrospective analysis of trastuzumab treatment beyond progression (applied in 46% of patients in the H+D group and 37% in the H→D group) showed a correlation with longer overall survival in both treatment arms (36.0 vs. 18.0 months and 30.3 vs. 18.6 months, respectively). CONCLUSION: First-line treatment in patients with MBC with H→D resulted in a similar PFS compared with H+D, but the response rate was lower and the overall survival nonsignificantly shorter.

Physician-staffed HEMS dispatch in the Netherlands: Adequate deployment or minimal utilization?

INTRODUCTION: In the Netherlands, a physician-staffed helicopter emergency medical system (HEMS), called the Helicopter Mobile Medical Team (HMMT), provides prehospital care for severely injured patients in addition to ambulance services. This HMMT has proven to increase chances of survival and reduce morbidity. HMMT dispatch is performed following certain dispatch criteria. The goal of this study was to analyze actual dispatch rates and assess the protocol adherence of the emergency dispatchers in Rotterdam regarding HMMT dispatch. METHODS: All high priority ambulance runs between April 1 and July 1, 2003, were prospectively documented and cross-referenced to dispatch criteria. It was determined whether the emergency call warranted either immediate dispatch of the HMMT or a secondary dispatch after arrival of the first ambulance. When dispatch actually occurred, this was also documented. RESULTS: In The Studied Period A Total Of 5765 A1 Ambulance Runs During Daylight Were Documented. Of These, 1148 Runs Met Primary Dispatch Criteria And 38 Runs Met Secondary Dispatch Criteria. Actual Hmmt Dispatch Occured In 162/1186 (14%) Cases. CONCLUSIONS: HEMS dispatch rates and dispatch criteria adherence are low (14%). Better protocol adherence by emergency dispatchers could lead to a sevenfold increase of HMMT dispatches. The reasons for suboptimal protocol adherence remain unclear and persist, despite proven value of the HMMT in reducing patient mortality and morbidity.