Phase I study of temsirolimus in combination with cetuximab in patients with advanced solid tumours.

BACKGROUND: Preclinical studies suggest synergistic antitumour effects of mammalian target of rapamycin (mTOR) inhibitor such as temsirolimus combined with anti-EGFR monoclonal antibody such as cetuximab. METHODS: Temsirolimus (T) and cetuximab (C) were combined and escalated in cohorts of patients with advanced or metastatic solid tumours, respectively from 15 to 25 mg and 150-250 mg/m2, until the maximum tolerated dose (MTD) was determined. Effort was made in the expansion cohort to enrol patients harbouring a molecular aberration in the human epidermal growth factor receptor (EGFR) and/or phosphoinositide 3-kinase (PI3K) pathways. Paired biopsies were optional to evaluate pathway modulation. RESULTS: Among 39 patients enrolled, three experienced dose-limiting toxicities (DLTs): pulmonary embolism (C200 + T20), stomatitis (C250 + T20) and acneiform rash (C250 + T25). The weekly C 250 mg/m2 and T 25 mg dose level was selected as the MTD. The most common treatment-related adverse events were: acneiform rash (97%), oral mucositis (82%), fatigue (59%), nausea (41%) and diarrhoea (36%). The median progression-free survival (PFS) and overall survival (OS) were respectively 2.0 months [95% CI: 1.8, 3.5] and 7.5 months [95% CI: 5.5, 11.9]. Among all patients, partial responses (PRs) and stable diseases (SDs) were observed in 2 (5.1%) and 18 patients (46.2%), respectively. The objective response rate (ORR) in patients with a molecular aberration was 2/14 (14%), versus 0/24 in those without molecular aberration. CONCLUSIONS: Combination of T + C showed significant but manageable toxicities. Due to modest clinical activity, further evaluation is not recommended. Molecular selection could potentially increase the objective response rate and should be implemented during drug development.

Port catheter versus peripherally inserted central catheter for postoperative chemotherapy in early breast cancer: a retrospective analysis of 448 patients.

PURPOSE: We aimed to compare the complication rate between port catheters (PC) and peripherally inserted central catheters (PICC) for the administration of postoperative chemotherapy for breast cancer. METHODS: All patients treated from January 2010 to August 2012 at the Centre Henri Becquerel for early breast cancer requiring postoperative chemotherapy were retrospectively screened. The primary endpoint was the occurrence of a major complication related to the central venous catheter. Major complications were defined as any grade 3 event according to CTCAE 4.0, delay in chemotherapy >7 days, change of the device, life-threatening event, event requiring a hospitalization, or a prolongation of hospitalization. RESULTS: A total of 448 patients were included; 290 had a PC and 158 a PICC. Overall, 31 major complications related to the central venous catheter were observed: 13 for patients with a PC (4.5%) and 18 for patients with a PICC (11.4%). In univariate analysis, having a PICC was the only factor significantly associated with a higher risk of major complications (HR = 2.83, p = 0.0027). We observed a trend for a higher risk of major complications for patients older than 60 years or with BMI >25 (p = 0.06). In multivariate analysis, having a PICC was the only predictive factor of major complications (HR = 2.89, p = 0.004). CONCLUSIONS: In univariate and multivariate analysis, having a PICC instead of a PC was the only predictive factor of device-related major complication. If confirmed prospectively by the NCT02095743 ongoing trial, this result might modify the management of adjuvant chemotherapy administration.