Results from a monocentric phase II trial of erlotinib in patients with metastatic prostate cancer.

BACKGROUND: Erlotinib is an orally active small-molecule tyrosine kinase inhibitor targeted against human epidermal growth factor receptor 1/epidermal growth factor receptor (ErbB1), known to be overexpressed in a variety of cancers, including prostate cancer. PATIENTS AND METHODS: This was a phase II monocentric study of 30 patients with advanced or metastatic prostate cancer, 29 had castration-resistant prostate cancer and 23 had received prior chemotherapy. Patients received erlotinib: 150 mg/day, increased to 200 mg at week 4, and continued until progression or unacceptable toxicity. Efficacy was defined as a decrease or stabilization of prostate-specific antigen (PSA) without clinical progression. Clinical benefit was evaluated by Karnofsky performance status and pain intensity, and response was an improvement in one of these parameters without worsening in the other. RESULTS: Median age was 69 years (range 51-77 years), and median PSA 102 ng/ml (range 3-1213 ng/ml). Dose escalation to 200 mg was possible in 16 (55%) patients. Moderate toxicity was observed. No patient had a decrease in PSA, 14% had stabilization, less than the >or=20% expected. PSA-doubling time, evaluated before and after erlotinib, was increased for 10 patients (P = 0.0058). Clinical benefit was achieved in 40% of patients. CONCLUSION: Erlotinib demonstrated an improvement in clinical benefit. Future directions should include evaluating its use in less advanced prostate cancer.

Suspicion of pulmonary embolism in outpatients: nonspecific chest pain is the most frequent alternative diagnosis.

OBJECTIVES: Several recent studies have focused on identifying clinical predictors of embolism. However, although pulmonary embolism is ruled out in 70-85% of the patients in whom it is suspected, data on the clinical characteristics and discharge diagnosis of such patients are scarce. Our aim was to evaluate whether clinical characteristics would allow predicting alternative diagnoses other than pulmonary embolism thereby ruling out venous thromboembolism. DESIGN: Retrospective analysis. SETTING: Emergency centres of two teaching and general hospitals. SUBJECTS: A total of 1090 consecutive outpatients admitted for clinically suspected pulmonary embolism and a diagnosis established by a validated algorithm and a 3-month follow-up. OUTCOMES: Discharge diagnoses of patients in whom pulmonary embolism was ruled out were identified and regrouped into two categories: (i) nonspecific chest pain and (ii) diagnosis other than pulmonary embolism. Predictive accuracy of clinical and laboratory variables for diagnosing nonspecific chest pain was assessed by univariate and multivariate analysis. RESULTS: In patients without pulmonary embolism, nonspecific chest pain (parietal chest pain, chest pain of unknown origin and pleuritis) was the most frequent discharge diagnosis (n = 334, 31% of the entire cohort, 43% of the patients without pulmonary embolism). Other patients without pulmonary embolism had a wide variety of diagnoses, of which the most frequent were bronchopneumonia (6.0% of the entire cohort) and heart failure (5.2%). In the multivariate analysis, seven variables were strongly associated with nonspecific chest pain: younger age (below 40 years), female gender, respiratory rate below 20 min(-1), heart rate below 100 min(-1), and absence of recent immobilization, dyspnoea and haemoptysis. Two of the 24 patients in whom all those characteristics were present had pulmonary embolism (8%, 95% CI 3-22%). CONCLUSIONS: The most frequent discharge diagnosis in emergency ward patients in whom pulmonary embolism is ruled out is nonspecific chest pain. A clinical model did not allow to predict nonspecific chest pain with enough accuracy to rule out pulmonary embolism without further testing. Whether a more precise characterization of chest pain might allow an accurate identification of such patients deserves further study.