A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell lung cancer
| Autor: | Patricia O. McCarthy, Jeffrey Settleman, Alona Muzikansky, Jennifer S. Temel, Panos Fidias, Alice T. Shaw, Sreenath V. Sharma, Thomas J. Lynch, Subba R. Digumarthy, Jeffrey G. Supko, Lecia V. Sequist, Joel W. Neal, Sarah B. Goldberg, Rebecca S. Heist |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Lung Neoplasms Pharmacology Gastroenterology Tyrosine-kinase inhibitor 0302 clinical medicine Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols Medicine Tissue Distribution Epidermal growth factor receptor Enzyme Inhibitors 0303 health sciences biology Middle Aged Prognosis Rash 3. Good health ErbB Receptors Oncology Erlotinib 030220 oncology & carcinogenesis Female medicine.symptom Immunosuppressive Agents medicine.drug Hydroxychloroquine Pulmonary and Respiratory Medicine Adult medicine.medical_specialty Maximum Tolerated Dose medicine.drug_class Neutropenia Adenocarcinoma Article 03 medical and health sciences Internal medicine Humans Everolimus Lung cancer 030304 developmental biology Aged Neoplasm Staging Sirolimus business.industry Non–small-cell lung cancer medicine.disease respiratory tract diseases Mutation biology.protein business Follow-Up Studies |
| Zdroj: | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 7(10) |
| ISSN: | 1556-1380 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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