Methodology of phase II clinical trials in metastatic elderly breast cancer: a literature review.

PURPOSE: As the incidence of invasive breast cancer will increase with age, the number of elderly patients with a diagnosis metastatic breast cancer will also rise. But the use of cytotoxic drugs in elderly metastatic breast cancer patients is not systematic and is dreaded by medical oncologists. The need for prospective oncologic data from this population seems increasingly obvious. The main objective of this review is to investigate design and characteristics of phase II trials that assess activity and feasibility of chemotherapies in elderly advanced/metastatic breast cancer patients. METHODS: An electronic search in PUBMED allowed us to retrieve articles published in English language on phase II trials in elderly metastatic breast cancer between January 2002 and May 2016. Sixteen publications were finally included in this review. RESULTS: The primary endpoint was a simple, a composite, and a co-primary endpoints in 11, three, and two studies, respectively. Efficacy was the primary objective in 15 studies: simple (n = 10), composite (n = 3), co-primary endpoints (n = 2). Composite or co-primary endpoints combined efficacy and toxicity. Thirteen studies used multistage designs. CONCLUSIONS: Only five studies evaluated the feasibility, i.e., to jointly assess efficacy and tolerance to treatment (toxicity, quality of life, etc) as primary endpoint. Development of elderly specific phase III clinical trials might be challenging, it therefore seems essential to conduct phase II clinical trials evaluating jointly efficacy and toxicity in a well-defined geriatric population. Use of multistage designs that take into account heterogeneity would allow to identify a subpopulation at interim analysis and to reduce the number of patients exposed to an inefficient or a toxic treatment regimen. It is crucial to evaluate new therapies (targeted therapies, immunotherapies) using adequate methodologies (Study design, endpoint).

Transperineal versus transvaginal ultrasound cervical length measurement and preterm labor.

OBJECTIVE: The aim was to evaluate the agreement between and the reproducibility of transperineal and transvaginal ultrasound cervical length measurements performed by the duty obstetrical team in case of preterm labor. The acceptability of transperineal ultrasonography was also assessed. METHODS: Pregnant patients between 25 and 34 weeks of gestation with contractions and a clinically modified cervix were included. Order of ultrasonography examination (transperineal or transvaginal first) and rank of operator (resident or senior) were allocated randomly. Agreement was assessed using the intraclass correlation coefficient (ICC) and the Bland and Altman plot. The patient's discomfort and preference for either method were assessed with a questionnaire. RESULTS: 62 patients admitted for preterm labor between 25 and 34 weeks of gestation were included. Six seniors and nine residents took part in the study. Among the 51 patients with an interpretable transperineal ultrasound scan, median cervical length measurements with the transperineal and the transvaginal technique were, respectively, 25 mm (0-53) and 27 mm (4-51). Concordance was good with an ICC of 0.83 [IC 95 % = (0.73-0.90)]. Transperineal ultrasonography was preferred in 56.5 % of cases. CONCLUSION: In case of preterm labor, cervical length measurement with transperineal ultrasonography seems reproducible and can be performed by the obstetric team on duty.

Lanreotide Autogel 90 mg and lymphorrhea prevention after axillary node dissection in breast cancer: a phase III double blind, randomized, placebo-controlled trial.

AIM: The aim of this study was to assess the efficacy of Lanreotide Autogel 90 mg PR to prevent lymphorrhea after axillary dissection in breast cancer. METHODS: A Phase III double-blind, randomized, placebo-controlled trial was performed between April 1st, 2008, and December 31st, 2010. The primary endpoint was the lymphorrhea volume (ml) in the axillary drain during the first four postoperative days. The secondary end points were the number of days until axillary drain removal, hospital stay duration (days), lymphorrhea volume (ml) up to days 15, 30 and 180, number of cases with seroma aspiration and number of seroma aspirations, evaluation of wound, arm pain and mobility on days 15, 30 and 180. RESULTS: A total of 148 patients were recruited for the study. Altogether 145 patients were randomized and analysed on an intention-to-treat basis. On the day before surgery 73 patients received the placebo and 72 patients received lanreotide. At four postoperative days, there was a tendency towards a reduction of the lymphorrhea volume in the lanreotide group (median 292 ml, range 1-965 ml) as compared to the placebo group (median 337 ml, range 0-1230 ml), although it was not statistically significant (p = 0.18). There was no significant difference for the secondary end points. In the group with axillary dissection performed alone (n = 24), the lymphorrhea volume was shown to be significantly reduced in the lanreotide group, (p = 0.035) as compared to the placebo group. CONCLUSION: Our study did not identify any overall significant reduction of lymphorrhea on lanreotide.