Investigating the clinical impact of dose-banding for weekly paclitaxel in patients with breast cancer: A retrospective and monocentric study.

AIMS: Dose-banding (DB) consists in approximating the theoretical dose of anticancer drugs calculated according to the body surface area (Dose-BSA) of patients. This concept is supported by pharmacokinetic but not by clinical data. The aim of this study was to assess the clinical outcome of DB defined as dose-fitting up to ±10%. METHODS: This was a retrospective study conducted in patients receiving weekly paclitaxel in neoadjuvant (NAT) and metastatic (M+) settings. Three groups of patients were considered according to type of paclitaxel dosing: Dose-BSA, DB approximated down (DB-Low) and DB approximated up (DB-High). Efficacy was evaluated by the rate of pathological complete response for patients in NAT setting and by the median of progression-free survival plus overall survival for those in M+ setting. Toxicity and efficacy were compared in the 3 groups. RESULTS: A total of 224 and 209 patients were assessable in the M+ and NAT settings, respectively. A toxic event was observed for 31.7 and 27.3% in M+ and NAT, respectively. The rate of pathological complete response was 41.6% in NAT. The median progression-free survival was 5.2 (4.1-5.8) months and overall survival was 16.3 (14.6-18.4) months for patients in M+. Efficacy and toxicity were not different in DB-Low and DB-High groups compared to Dose-BSA group. CONCLUSION: DB with approximated doses up to ±10% does not seem to influence clinical outcome of patients treated with weekly paclitaxel. This is the first study to include clinical observations, which lends support to DB as a safe and effective dosing method.

Brentuximab vedotin in real life, a seven year experience in patients with refractory/relapsed CD30+ T cell lymphoma.

INTRODUCTION: Brentuximab vedotin (Bv) has been approved for the treatment of Refractory/Relapsed (R/R) Anaplastic Large Cell Lymphomas (ALCL) and cutaneous T-Cell Lymphomas, but is also effective in other CD30+ malignancies. We report here the outcomes of patients with various R/R Peripheral T Cell Lymphoma (PTCL) treated with Bv in real life practice. METHOD: This was a retrospective, single-center study based on medical records of patients with R/R PTCL treated either with Bv alone or in combination with chemotherapy. RESULTS: Among 27 patients treated with Bv, neutropenia was the main serious adverse event observed in particular when Bv was used as combination treatment. The complete Response Rates (CRR) was 40.7%; it was significantly improved when Bv was used as combination treatment. The majority of eligible patients (7/10) underwent Stem Cell Transplantation. Median Progression Free Survival (PFS) and Overall Survival (OS) were 5.2 months and 12.5 months respectively. CONCLUSION: Our current study shows that Bv used in combination with chemotherapy provides a high CRR and thereby allows SCT in R/R PTCL. The use of Bv treatments in this setting warrants further investigation.

Safety of oral hydration after cisplatin infusion in an outpatient lung cancer unit.

PURPOSE: Hydration is needed before and after cisplatin infusion for reducing the risk of nephrotoxicity. Even though there is no standard regimen, patients receive mostly intravenous hydration before and after cisplatin leading hospitalization during at least one night. Since the feasibility has been published, oral hydration after cisplatin was implemented in our practice. The safety of this new way of hydration needs to be assessed in clinical practice. METHODS: We collected medical records from patients treated by cisplatin for lung cancer in our unit between 2010 and 2016. We retrospectively analyzed the incidence of cisplatin induced nephrotoxicity between after and before the change of hydration regimen. RESULTS: Our patient cohort included 241 patients hydrated by intravenous regimen (IV/IV group) and 276 patient hydrated by intravenous and oral regimen (IV/PO group). Grade ≥ 1 nephrotoxicity occurred in 39.4 and 25.7% in the IV/IV and IV/PO groups respectively (p = 0.001). Age over 70 at baseline was a predictive factor for nephrotoxicity, but not estimated glomerular filtration rate nor cisplatin-associated drugs. After a multivariate analysis, age remained a predictive factor for nephrotoxicity and IV/PO hydration associated with a decrease in nephrotoxic risk. CONCLUSION: The implementation of oral hydration in our practice was not associated with an increase in nephrotoxicity. Our observation based on large data from clinical practice shows that oral hydration after cisplatin is safe.

Life-threatening complications after high-dose methotrexate and the benefits of glucarpidase as salvage therapy: a cohort study of 468 patients.

The aims of this study were to characterize the incidence and outcomes of severe toxicities following the administration of high-dose methotrexate (HD-MTX; ≥1 g/m2). Among the 468 patients included in the study, 69 (14.9%) developed at least one episode of acute kidney injury (AKI; 138/1264 HD-MTX administrations), including 34 (7.2%) who developed KDIGO stage 2-3 AKI. The three baseline factors independently associated with the risk of developing AKI were age, body mass index and a diagnosis of acute lymphoblastic leukemia. Higher plasma MTX concentration was associated with AKI and extra-renal toxicities. Notwithstanding potentially confounding factors, most patients with AKI who received glucarpidase (n = 41) developed extra-renal toxicity (leading to the death of two patients) despite early administration. Thus, severe toxicity and death can occur whether or not glucarpidase is administered, which confirms the need for further interventional studies to provide greater precision on its role in the management of HD-MTX toxicity.

Assessment of efficacy of postinfusion tubing flushing in reducing risk of cytotoxic contamination.

PURPOSE: Infusion of cytotoxic drugs carries the risk of occupational exposure of healthcare workers. Since disconnecting an infusion line is a source of contamination, flushing of tubing after infusion of cytotoxic agents is recommended, but the optimal volume of rinsing solution is unknown. The objective of this study was to assess whether postinfusion line flushing completely eliminates cytotoxics. METHODS: Infusions were simulated with 3 cytotoxics (gemcitabine, cytarabine, and paclitaxel) diluted in 5% dextrose injection or 0.9% sodium chloride injection in 250-mL infusion bags. Infusion lines were flushed using 5% dextrose injection or 0.9% sodium chloride solution at 2 different flow rates. The remaining concentration of cytotoxics in the infusion line was measured by a validated high-performance liquid chromatography (HPLC) method after passage of every 10 mL of flushing volume until a total of 100 mL had been flushed through. RESULTS: All cytotoxics remained detectable even after line flushing with 80 mL of flushing solution (a volume 3-fold greater than the dead space volume within the infusion set). Gemcitabine and cytarabine were still quantifiable via HPLC even after flushing with 100 mL of solution. Efficacy of flushing was influenced by the lipophilicity of drugs but not by either the flushing solvent used or the flushing flow rate. After 2-fold dead space volume flushing, the estimated amount of drug remaining in the infusion set was within 0.19% to 0.56% of the prescribed dose for all 3 cytotoxics evaluated. CONCLUSION: Complete elimination of cytotoxics from an infusion line is an unrealistic objective. Two-fold dead space volume flushing could be considered optimal in terms of administered dose but not from an environmental contamination point of view. Even when flushed, the infusion set should still be considered a source of cytotoxic contamination.