Risk Prediction Tools Available for Germline BRCA1/2 Mutations Underperform in Prostate Cancer Patients.

Early identification of germline BRCA1/2 mutations may be relevant for the management of patients with prostate cancer (PC) and to prevent future breast and ovarian cancers in their relatives. Several prediction tools have been developed to estimate the likelihood of a germline BRCA1/2 mutation and are widely used to optimize screening in breast and ovarian cancer patients. We aimed to elucidate the proportion of PC patients with known BRCA1/2 mutations who would have qualified for testing using two risk calculation models (BRCAPRO and the Manchester scoring system [MSS]). We analyzed 106 families with known BRCA1/BRCA2 mutations, including 23 with PC cases. Only 30% and 48% of PC patients who were known BRCA1/BRCA2 mutations carriers would have qualified for testing using BRCAPRO and MSS, respectively. A median of two breast and/or ovarian cancer cases per family had occurred between the first PC identified in a carrier and the cancer case leading to germline testing. PATIENT SUMMARY: We tested two models developed to predict the probability of inherited BRCA1/BRCA2 mutations and found that these tools underperform in men with prostate cancer and should not be used to optimize testing in this population.

Efficacy and safety of weekly paclitaxel combined with cetuximab in the treatment of pretreated recurrent/metastatic head and neck cancer patients.

INTRODUCTION: The addition of cetuximab to weekly paclitaxel has demonstrated high efficacy in the first-line treatment of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). However, this combination has been widely extended to patients who present resistance to first line chemotherapy (CT) or those who are not candidates for platinum-based CT. MATERIAL AND METHODS: We have retrospectively analyzed the efficacy and safety of cetuximab in combination with weekly paclitaxel in patients with R/M-SCCHN who present disease progression after platinum schedules or those who were not candidates for platinum-based CT. Patients received weekly paclitaxel 80mg/m(2) and cetuximab 250mg/m(2) (initial dose of 400mg/m(2)) until progression or unacceptable toxicity. RESULTS: Twenty-two patients were included. Median age was 58 (43-68), ECOG PS (0/1/2): 6/10/4, 19 patients had received prior platinum-based treatment (nine patients were platinum-sensitive and nine were platinum-refractory). With a median follow-up of 6.18months (range 1.3-29.7), overall response rate (ORR) was 55% (95% CI 31-76%):1 (5%) complete response and 9 (50%) partial responses. Median duration of response was 10.23months. Median progression free survival (PFS) and overall survival (OS) were 5.4 and 9.1months, respectively. There were no differences in response rate according to platinum sensitivity (66% sensitive vs 44% refractory; P=0.61). The main toxicity consisted of rash in 70% of patients (5% grade 3), with an association between rash severity and ORR (grade 0-1: 33% vs grade 2-3: 64%; P=0.03) and a trend for better PFS and OS. CONCLUSION: Weekly paclitaxel in combination with cetuximab is a well tolerated and highly active second-line treatment in patients with R/MSCCHN who experience disease progression after platinum-based CT, including those who present resistant disease. Our results suggest that the efficacy of this combination is apparently superior than the published data on single agent cetuximab in this setting.