Dataset Information

Phase I Study of Intermittent High-Dose Lapatinib Alternating with Capecitabine for HER2-Positive Breast Cancer Patients with Central Nervous System Metastases.

ABSTRACT:

Purpose

Lapatinib and capecitabine cross the blood-tumor barrier in breast cancer brain metastasis but have modest clinical efficacy. Administration of high-dose tyrosine kinase inhibitor has been evaluated in brain metastases and primary brain tumors as a strategy to improve drug exposure in the central nervous system (CNS). We derived a rational drug scheduling of intermittent high-dose lapatinib alternating with capecitabine based on our preclinical data and Norton-Simon mathematical modeling. We tested this intermittent, sequential drug schedule in patients with breast cancer with CNS metastasis.

Patients and methods

We conducted a phase I trial using an accelerated dose escalation design in patients with HER2-positive (HER2⁺) breast cancer with CNS metastasis. Lapatinib was given on day 1-3 and day 15-17 with capecitabine on day 8-14 and day 22-28 on an every 28-day cycle. Lapatinib dose was escalated, and capecitabine given as a flat dose at 1,500 mg BID. Toxicity and efficacy were evaluated.

Results

Eleven patients were enrolled: brain only (4 patients, 36%), leptomeningeal (5 patients, 45%), and intramedullary spinal cord (2 patients, 18%). Grade 3 nausea and vomiting were dose-limiting toxicities. The MTD of lapatinib was 1,500 mg BID. Three patients remained on therapy for greater than 6 months.

Conclusions

High-dose lapatinib is tolerable when given intermittently and sequentially with capecitabine. Antitumor activity was noted in both CNS and non-CNS sites of disease. This novel administration regimen is feasible and efficacious in patients with HER2⁺ breast cancer with CNS metastasis and warrants further investigation.

SUBMITTER: Morikawa A

PROVIDER: S-EPMC6773251 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

Phase I Study of Intermittent High-Dose Lapatinib Alternating with Capecitabine for HER2-Positive Breast Cancer Patients with Central Nervous System Metastases.

Morikawa Aki A de Stanchina Elisa E Pentsova Elena E Kemeny Margaret M MM Li Bob T BT Tang Kendrick K Patil Sujata S Fleisher Martin M Van Poznak Catherine C Norton Larry L Seidman Andrew D AD

Clinical cancer research : an official journal of the American Association for Cancer Research 20190415 13

<h4>Purpose</h4>Lapatinib and capecitabine cross the blood-tumor barrier in breast cancer brain metastasis but have modest clinical efficacy. Administration of high-dose tyrosine kinase inhibitor has been evaluated in brain metastases and primary brain tumors as a strategy to improve drug exposure in the central nervous system (CNS). We derived a rational drug scheduling of intermittent high-dose lapatinib alternating with capecitabine based on our preclinical data and Norton-Simon mathematical ...[more]

PMID: 30988080

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Dataset Information

Phase I Study of Intermittent High-Dose Lapatinib Alternating with Capecitabine for HER2-Positive Breast Cancer Patients with Central Nervous System Metastases.

Purpose

Patients and methods

Results

Conclusions

Publications

Phase I Study of Intermittent High-Dose Lapatinib Alternating with Capecitabine for HER2-Positive Breast Cancer Patients with Central Nervous System Metastases.

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