EGFR kinase domain mutation positive lung cancers are sensitive to intrapleural perfusion with hyperthermic chemotherapy (IPHC) complete treatment.

Hongjuan Zhang,Aiqun Zhang,Kaifeng Xu,Cheng Zhan,Zhirong Shen,Liang Chen,Zhiqiang Xue,Lei Yu,Ji Ke

doi:10.18632/oncotarget.6491

Abstract

Lung cancer is the global leading cause of cancer-related deaths. A significant portion of lung cancer patients harbor kinase domain mutations in the epidermal growth factor receptor (EGFR). While EGFR tyrosine kinase inhibitors (TKI) effectively shrink tumors harboring mutant EGFR, clinical efficacy is limited by the development of TKI resistance. Effective alternatives are desperately needed in clinic for treating EGFR kinase domain mutation positive lung cancer. In our clinic in treating M1a lung cancer patients through intrapleural perfusion with hyperthermic chemotherapy (IPHC) followed by cycles of systemic chemotherapy (we termed this procedure IPHC complete treatment, IPHC-CT), we found dramatic tumor shrinkage in mutant EGFR-positive patients. We further confirmed the sensitivity of EGFR mutation-positive lung cancer cell lines derived from patients to HC (hyperthermic chemotherapy) treatment. We found that hyperthermia promoted accumulation of cisplatin in lung cancer cells. Hyperthermia and cisplatin synergistically downregulated the EGFR protein level, leading to quenching of signal from EGFR and induction of apoptosis. Our work therefore showed IPHC-CT is an effective treatment for EGFR kinase domain mutation positive lung cancer patients.

Highlights

Non-small cell lung cancer (NSCLC), consisting of lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, is the major pathological type of lung cancer
Patients positive for epidermal growth factor receptor (EGFR) kinase domain mutation benefited from intrapleural perfusion with hyperthermic chemotherapy (IPHC)-CT treatment
The patient was in good health for four years until lung CT revealed tumor nodules in left lung in 2013 and the patient began taking icotinib, an EGFR inhibitor approved for clinical usage by China Food and Drug Administration (CFDA) [17, 18]

Summary

INTRODUCTION

Non-small cell lung cancer (NSCLC), consisting of lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, is the major pathological type of lung cancer. A significant portion of lung cancer patients harbor kinase domain mutations in the epidermal growth factor receptor (EGFR) [4, 5] which sensitizes lung cancer cells to EGFR tyrosine kinase inhibitors (TKI) [6, 7]. An effective alternative therapy is desperately needed for lung cancer patients positive for EGFR kinase domain mutations. We report our clinical data to show that EGFR kinase domain mutation-positive NSCLC is associated with dramatic regression of patient’s tumor to IPHC followed by cycles of systemic chemotherapy (IPHCCT) and longer overall survival. EGFR mutation positive lung cancer cell lines showed enhanced ability to accumulate cisplatin in cell during hyperthermic treatment. Our work illustrates that IPHC-CT should be recommended for EGFR mutation positive lung cancer patients

RESULTS

DISCUSSION

Ethics statement

Surgical procedure