Elsevier

Journal of Thoracic Oncology

Volume 7, Issue 10, October 2012, Pages 1602-1608
Journal of Thoracic Oncology

Original Articles
A Phase I Study of Erlotinib and Hydroxychloroquine in Advanced Non–Small-Cell Lung Cancer

https://doi.org/10.1097/JTO.0b013e318262de4aGet rights and content
Under an Elsevier user license
open archive

Introduction

This investigator-initiated study explores the safety, maximum tolerated dose, clinical response, and pharmacokinetics of hydroxychloroquine (HCQ) with and without erlotinib in patients with advanced non–small-cell lung cancer.

Methods

Patients with prior clinical benefit from an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor were randomized to HCQ or HCQ plus erlotinib in a 3 + 3 dose-escalation schema.

Results

Twenty-seven patients were treated, eight with HCQ (arm A) and 19 with HCQ plus erlotinib (arm B). EGFR mutations were detected in 74% of the patients and 85% had received two or more prior therapies. Arm A had no dose-limiting toxicities, but the maximum tolerated dose was not reached as this arm closed early to increase overall study accrual. In arm B, one patient each experienced grade 3 rash, nail changes, skin changes, nausea, dehydration, and neutropenia; one had grade 4 anemia; and one developed fatal pneumonitis, all considered unrelated to HCQ. There were no dose-limiting toxicities, therefore the highest tested dose for HCQ with erlotinib 150 mg was 1000 mg daily. One patient had a partial response to erlotinib/HCQ, for an overall response rate of 5% (95% confidence interval, 1–25). This patient had an EGFR mutation and remained on therapy for 20 months. Administration of HCQ did not alter the pharmacokinetics of erlotinib.

Conclusions

HCQ with or without erlotinib was safe and well tolerated. The recommended phase 2 dose of HCQ was 1000 mg when given in combination with erlotinib 150 mg.

Key Words

Non–small-cell lung cancer
Erlotinib
Hydroxychloroquine

Cited by (0)

Disclosure: This work was supported by Genentech and the Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer, National Cancer Institute P50 CA090578 (JES).

Joel Neal received research funding from Genentech. Panos Fidias is on the advisory board for Genentech. Alice Shaw has consulted for Pfizer, Ariad, Chugai, Novartis, Millenium, and Daiichi. Thomas Lynch is a consultant for Merck, Supergen, and Boehringer-Ingelheim, is on the Board of Directors for Infinity, and is a joint holder for a patent for EGFR mutation testing. Sreenath Sharma received a grant from the LUNGevity Foundation & Goldman Philanthropic Partnerships, consulted for Concert Pharmaceuticals, and is employed by Norvartis. Jeffrey Settleman is employed by Genentech. Lecia Sequist received a grant from Genentech and is on the advisory boards for Clovis Oncology, Celgene, GSK, Daiichi Sankyo, and Merrimack. The remaining authors declare no conflict of interest.