Moe Tsuda1, Hiroshi Ishiguro2, Naoko Toriguchi3, Norikazu Masuda4, Hiroko Bando5, Masahiro Ohgami6, Masato Homma7, Satoshi Morita8, Naohito Yamamoto9, Katsumasa Kuroi10, Yasuhiro Yanagita11, Toshimi Takano12, Satoru Shimizu13, Masakazu Toi1. 1. Department of Breast Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 2. Breast Oncology Service, Saitama Medical University International Medical Center, Hidaka, Japan. 3. Oncology Products, Medicine Development Unit Japan, Eli Lilly Japan K.K, Kobe, Japan. 4. Department of Surgery, Breast Oncology, NHO Osaka National Hospital, Osaka, Japan. 5. Breast and Endocrine Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 6. Department of Pharmacy, Ibaraki Prefectural Central Hospital, Kasama, Japan. 7. Department of Pharmaceutical Sciences, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 8. Department of Biomedical Statistics and Bioinformatics. Graduate School of Medicine, Kyoto University, Kyoto, Japan. 9. Division of Breast Surgery, Chiba Cancer Center, Chiba, Japan. 10. Department of Breast Surgery, Tokyo Metropolitan Health and Hospitals Corporation Ebara Hospital, Tokyo, Japan. 11. Department of Breast Oncology, Gunma Prefectural Cancer Center, Gunma, Japan. 12. Breast Medical Oncology, Breast Oncology Center, The Cancer Institute Hospital of JFCR, Tokyo, Japan. 13. Breast and Endocrine Surgery, Kanagawa Cancer Center, Yokohama, Japan.
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 withlapatinib. 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.
RCT Entities:
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 cancerpatients 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.
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