Overnight fasting before lapatinib administration to breast cancer patients leads to reduced toxicity compared with nighttime dosing: a retrospective cohort study from a randomized clinical trial. (23rd October 2020)

• Record Type: Journal Article
• Authors: Tsuda, Moe; Ishiguro, Hiroshi; Toriguchi, Naoko; Masuda, Norikazu; Bando, Hiroko; Ohgami, Masahiro; Homma, Masato; Morita, Satoshi; Yamamoto, Naohito; Kuroi, Katsumasa; Yanagita, Yasuhiro; Takano, Toshimi; Shimizu, Satoru; Toi, Masakazu
• Is Part Of: Cancer medicine. Volume 9:Number 24(2020)
• Page Start: 9246
• Page End: 9255
• Publication Date: 2020-10-23
• Subjects: breast cancer -- drug discovery and delivery -- medical oncology -- quality of life -- Tyrosine kinase inhibitors; 616.994005
• DOI: 10.1002/cam4.3528
• Languages: English
• ISSNs: 2045-7634

Abstract

Abstract: Background: The bioavailability of lapatinib is affected by food, even following the 1 hour fast recommended by the package insert. We hypothesized that overnight fasting would minimize food‐drug interactions. Here, we investigated if lapatinib administration timing is associated with its tolerability, efficacy, and pharmacokinetics. Methods: This is a retrospective cohort study utilizing the medical records of patients enrolled in the JBCRG‐16/Neo‐LaTH randomized phase 2 trial for breast cancer patients treated with lapatinib. Lapatinib administration timing was divided into three groups: before breakfast (BB), between meals (BM), and at bedtime (AB). Side effects (SE), treatment discontinuation rate (TDR), relative dose intensity (RDI), pathological complete response (pCR) rate, and lapatinib serum trough concentration were compared between groups. Results: About 140 patients were included in this study: BB 15, BM 51, and AB 74. A reduced risk of diarrhea {adjusted hazard ratio (HR), 0.51, 95% confidence interval (CI), 0.27‐0.89, p = 0.018}, and rash {adjusted HR, 0.37; 95% CI, 0.17‐0.70, p = 0.002} was seen in BB versus AB. Fewer patients with low RDI (< 0.85/<0.6) were in the BB group (BB 13% / 0%, BM 22% / 3.9%, AB 24% / 14%, p = 0.70 / 0.11). pCR was not diminished ( p = 0.75). BB group had the lowest serum lapatinib concentration and variability (mean ±SD were 0.35 ± 0.15, 0.65 ± 0.32, 0.96 ± 0.43 µg/ml). Conclusions: Compared to bedtime administration, lapatinib administration after overnight fasting reduces its toxicity without diminishing its therapeutic efficacy. Abstract : The bioavailability of lapatinib is affected by food, even when following package insert information. In a retrospective cohort study that utilized the medical records of 140 patients enrolled in the JBCRG‐16/Neo‐LaTH randomized phase 2 trial for breast cancer who were treated with lapatinib, associations between the timing of lapatinib administration (before breakfast, between meals or at bedtime) and clinical outcomes such as toxicities likely due to lapatinib (diarrhea, skin rash and hepatotoxicity) and drug efficacy were evaluated. Lapatinib administration after overnight fasting reduced the incidence of drug‐related diarrhea and skin rash without diminishing its therapeutic efficacy by avoiding food‐drug interactions.