Endocrine therapy or chemotherapy as first-line therapy in hormone receptor-positive HER2-negative metastatic breast cancer patients.

BACKGROUND: For hormone receptor-positive (HR+) human epidermal growth factor receptor 2 (HER2-) negative metastatic breast cancer (MBC), international guidelines recommend endocrine therapy as first-line treatment, except in case of 'visceral crisis'. In the latter case, chemotherapy is preferred. Few studies have compared these two strategies. We used the Epidemiological Strategy and Medical Economics (ESME) programme, UNICANCER, a large national observational database (NCT03275311), to address this question. METHODS: All patients who initiated treatment for a newly diagnosed HR+ HER2-negative MBC between January 2008 and December 2014 in any of the 18 French Comprehensive Cancer Centers participating to ESME were selected. Patients should be aromatase inhibitor (AI)-sensitive (no previous AI or relapse occurring more than 1 year after last adjuvant AI). Objectives of the study were evaluation of progression-free and overall survival (OS) according to the type of first-line treatment adjusted on main prognostic factors using a propensity score. RESULTS: Six thousand two hundred sixty-five patients were selected: 2733 (43.6%) received endocrine therapy alone, while 3532 (56.4%) received chemotherapy as first-line therapy. Among the latter, 2073 (58.7%) received maintenance endocrine therapy. Median OS was 60.78 months (95% confidence interval [CI], 57.16-64.09) and 49.64 months (95% CI, 47.31-51.64; p < 0.0001) for patients receiving endocrine therapy alone and chemotherapy ± maintenance endocrine therapy, respectively. However, this difference was not significant after adjusting on the propensity score (hazard ratio: 0.943, 95% CI 0.863-1.030, p = 0.19). CONCLUSION: In this large retrospective cohort of patients with AI-sensitive metastatic luminal BC, OS was similar, whether first-line treatment was chemotherapy or endocrine therapy. In agreement with international guidelines, endocrine therapy should be the first choice for first-line systemic treatment for MBC in the absence of visceral crisis.

Prevalence, risk factors and clinical implications of malnutrition in French Comprehensive Cancer Centres.

BACKGROUND: This epidemiological observational study aimed at determining the prevalence of malnutrition in non-selected adults with cancer, to identify risk factors of malnutrition and correlate the results with length of stay and 2-month mortality. METHODS: This prospective multicentre 1-day study conducted in 17 French Comprehensive Cancer Centres included 1545 patients. Body mass index (BMI), weight loss (WL) in the past 6 months and age were routinely recorded according to the French national recommendations for hospitalised patients; malnutrition was rated as absent, moderate or severe according to the level of WL and BMI. Age, sex, tumour site, type of hospitalisation and treatment, disease stage, World Health Organisation performance status (PS) and antibiotic therapy were the potential malnutrition risk factors tested. Follow-up at 2 months allowed to determine the correlation with length of stay and mortality. RESULTS: Malnutrition was reported in 30.9% of patients, and was rated as severe in 12.2%. In multivariate analysis, only pre-existing obesity (BMI> or =30), PS > or =2 and head-and-neck or upper digestive cancers were associated with increased risk of malnutrition. Antibiotics use was significantly higher in malnourished patients (35.5 vs 22.8%; P<0.001). Severe malnutrition was independently associated with mortality. The median length of stay was 19.3+/-19.4 days for malnourished patients vs 13.3+/-19.4 days for others (P<0.0001). CONCLUSION: In French Comprehensive Cancer Centres, one out of three cancer patients are malnourished and this was associated with a longer length of stay. Pre-existing obesity could be identified as a new risk factor for malnutrition in our cancer patient population perhaps because of a misidentification or a delay in nutrition support in this category of patients.

Dexamethasone as a probe for CYP3A4 metabolism: evidence of gender effect.

BACKGROUND: A study was conducted to evaluate prospectively the correlation between docetaxel clearance and pharmacokinetics of dexamethasone previously obtained in 21 patients. PATIENTS AND METHODS: Dexamethasone pharmacokinetics were performed in 17 patients 24 h before docetaxel treatment as monochemotherapy. Dexamethasone and docetaxel plasma concentrations were determined by HPLC methods. Determination of docetaxel unbound fraction in plasma was performed using microequilibrium dialysis. RESULTS: Significant correlation was observed between observed plasma docetaxel clearances (CL(docetaxel)) and values predicted from dexamethasone plasma clearance (CL(dexa)), unbound plasma docetaxel fraction estimated from serum alpha1-acid glycoprotein level (fu(alpha1-AAG)), and hepatic metastasis status. However, after splitting of the prospective data set according to gender, no correlation was observed for males (R(2) = 0.08, NS, n = 10), then strong correlation was observed for females (R(2) = 0.78, P < 0.01, n = 7). Multivariate analysis was performed from data obtained in the women included in the first study and those of this prospective study (n = 18). Docetaxel CL was significantly correlated with CL(dexa) (P = 0.001) and fu(alpha1-AAG) (P = 0.01) according to the relationship (with +/-95% confidence intervals): CL(docetaxel) (l/h) = 1.92 (+/-0.94) x CL(dexa) (l/h) + 2.68 (+/-1.95) x fu(alpha1-AAG) (%) (R(2) = 0.68). CONCLUSION: Dexamethasone may be used to predict docetaxel clearances in females, but not in males.

Randomized clinical trial comparing axillary padding with closed suction drainage for the axillary wound after lymphadenectomy for breast cancer.

BACKGROUND: After axillary lymphadenectomy for breast cancer, a suction drain is routinely inserted into the axilla to prevent seroma formation. This drain is an obstacle to reducing hospital stay after breast-conserving surgery. This was a prospective randomized clinical trial to assess the safety and results of axillary padding without the use of a drain. METHODS: Between May 2001 and August 2003, 100 women were randomly allocated axillary padding without a drain or with the use of an axillary suction drain. Prospective assessments were made of morbidity, pain, shoulder mobility, quality of life and medical costs including length of hospital stay. RESULTS: Using axillary padding significantly reduced the mean (s.d.) length of hospital stay (1.8(1) versus 4.5(2) days, P < 0.001). Postoperative complications, pain, shoulder mobility and quality of life were similar in the two groups. There was no difference in the duration of the two procedures. CONCLUSION: Axillary padding after axillary lymphadenectomy was feasible and safe, without a drain, and shortened hospital stay.

Cost-effectiveness analysis of two strategies for typing unrelated donors for bone marrow transplantation in France.

Large Registries of HLA-typed potential volunteer donors have been set up in numerous countries to find HLA-matched unrelated bone marrow donors. This study compared two strategies medicoeconomically for HLA typing in the context of a bone marrow volunteer donor Registry. It investigated the cost-effectiveness of strategies before and after the French Registry was modified in January 1999: HLA- A, B typing only at registration and secondary HLA-DR typing on part of the Registry (AB strategy) vs. typing at once for HLA- A, B, and DR (ABDR strategy). The point of view considered was that of payers, French typing tariffs with a 5% discount rate were used, effectiveness was defined as identification of at least one donor with no HLA-A, B, DR incompatibilities for a given recipient (compatible potential donor), the observation period was 9 months, and the judgement criterion was the differential cost-effectiveness ratio. The ABDR strategy identified 94.7% (142/150) of compatible potential donors. The differential cost-effectiveness ratio between the two strategies was 387,005 francs (Euro 58,995) for one supplementary compatible potential donor. Compared with a "do nothing" policy, the ratio was 3,744,087 francs (Euro 570,745) for the AB strategy vs. 576,136 francs (Euro 87,826) for the ABDR strategy. The ABDR strategy is thus more effective but also more costly than the AB strategy. Nevertheless, because of its lower effectiveness and the size of available ABDR Registries, the AB strategy will become obsolete.