A phase I study of erlotinib in combination with chemoradiation (CRT) for unresectable, locally advanced non-small cell lung cancer (NSCLC)

Abstract

7113 Background: Erlotinib(ER) is an inhibitor of epidermal growth factor receptor tyrosine kinase(EGFR-TK) approved for second line treatment of locally advanced or metastatic NSCLC. Preclinical studies indicate that small molecule inhibitors of EGFR-TK enhance the effects of ionizing radiation. Objective: To determine the maximum tolerated dose of ER that can be administered with standard CRT for NSCLC. Methods: Patients (pts) with unresectable stage III NSCLC enrolled in this 2-arm phase I dose-escalation study. Arm A included CRT with cisplatin(50mg/m2 IV d1,8,29,36), etoposide(50mg/m2 IV d1–5,29–33), chest radiation therapy(RT) (2Gy QD, Total 66cGy) & daily oral ER for 7 weeks followed by docetaxel(75mg/m2 IV Q21d) for 3 cycles. Arm B included induction paclitaxel(200mg/m2 d1) & carboplatin(AUC=6 d1) for two 21-day cycles then CRT with weekly paclitaxel(50mg/m2), weekly carboplatin (AUC=2), RT (2Gy QD, Total 66cGy) & daily ER for 7 weeks. In both arms, the ER dose was escalated from 50 to 150mg/day. Results: Twenty-five pts were enrolled and treated. Patient characteristics: ECOG performance status (0 in 17 pts, 1 in 6 pts, 2 in 1 pt.), median age 62 (range 51–78), gender male 15, female 10. For arm A (n=11), grade 3 toxicities during CRT were: esophagitis(4), thrombocytopenia(2) and pulmonary infiltrate(1). For arm B (n=14), grade 3 toxicities during CRT were: esophagitis(4), thrombocytopenia(1) and bilirubin(1). Grade 3/4 leukopenia was noted in both arms, but was not clinically significant. DLT has not been noted in either arm. Overall responses were (Arm A/B): Partial Response (A3/B6), Stable Disease (A5/B5), Progressive Disease (A2/B2), Not Evaluable (A1/B0). Conclusions: The addition of ER to two standard CRT regimens is feasible and does not appear to increase in-field toxicities. ER plus CRT warrants further examination in a phase II trial. Supported by NCI-P30 CA14599–28 & N01 CM17102–02 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech