Dataset Information

Phase I study and biomarker analysis of lapatinib and concurrent radiation for locally advanced breast cancer.

ABSTRACT:

Purpose

This phase I study assessed the toxicity and safety of combining daily lapatinib with radiation therapy. Sequential tumor biopsies were obtained to evaluate changes in biomarkers, such as epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2) signaling pathways.

Methods

Eligibility for this dose-escalation study included unresectable and locally recurrent or chemotherapy-refractory and locally advanced breast cancer, and adequate organ function. Patients underwent three serial biopsies: at baseline, after 1 week of lapatinib alone, and after 1 week of lapatinib and radiation. Endpoints included determination of toxicity, maximum tolerated dose, and analysis of the effect of lapatinib with or without radiation on EGFR and HER2 signaling pathways by immunohistochemistry.

Results

Doses of lapatinib up to 1,500 mg/day were well tolerated. Toxicity of grade 3 or more was limited to radiation dermatitis and pain. Out of 19 patients treated, in field responses per response evaluation criteria in solid tumors criteria were complete in four patients and partial in six patients. Serial biopsies were obtained in 16 patients with no complications. Total Her2 was relatively unchanged while phospho-Her2, phospho-Akt, and phospho-ERK showed variable responses to both lapatinib alone and dual therapy with lapatinib and radiation.

Conclusions

The combination of lapatinib and radiation was well tolerated in this patient cohort. Overall local response rates were comparable to those reported in other studies in this patient population. Biopsies were safely performed at all time points. Inhibition of HER2 and downstream signaling pathways was identified, although no strong correlation with response was seen.

SUBMITTER: Kimple RJ

PROVIDER: S-EPMC3528381 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Phase I study and biomarker analysis of lapatinib and concurrent radiation for locally advanced breast cancer.

Kimple Randall J RJ Horton Janet K JK Livasy Chad A CA Shields Janiel M JM Lawrence Julia A JA Chiu Wingkeung M WM Ivanova Anastasia A Ollila David W DW Carey Lisa A LA Halle Jan S JS Sartor Carolyn I CI Dees E Claire EC

The oncologist 20120924 12

<h4>Purpose</h4>This phase I study assessed the toxicity and safety of combining daily lapatinib with radiation therapy. Sequential tumor biopsies were obtained to evaluate changes in biomarkers, such as epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2) signaling pathways.<h4>Methods</h4>Eligibility for this dose-escalation study included unresectable and locally recurrent or chemotherapy-refractory and locally advanced breast cancer, and adequate organ function. Patients underwent ...[more]

PMID: 23006498

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Dataset Information

Phase I study and biomarker analysis of lapatinib and concurrent radiation for locally advanced breast cancer.

Purpose

Methods

Results

Conclusions

Publications

Phase I study and biomarker analysis of lapatinib and concurrent radiation for locally advanced breast cancer.

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