Intrapatient dose escalation to 800 mg/m2 pemetrexed is safe and feasible in patients with advanced non-small cell lung cancer (NSCLC) who have had prior chemotherapy

Abstract

7107 Background: Pemetrexed has proven clinical benefit in advanced NSCLC after prior chemotherapy. The aim of this open-label single-arm phase II study (H3E-AA-S037) is to determine the response rate, feasibility and safety of tailored dosing of pemetrexed in patients (pts) with previously treated advanced NSCLC. Methods: Major eligibility criteria included histologic or cytologic diagnosis of NSCLC; Stage IIIB or IV disease; one prior chemotherapy regimen for palliative therapy of locally advanced or metastatic disease; ECOG performance status 0 or 1; written informed consent. Pemetrexed was administered on day 1 of 21-day cycles. A dose of 500 mg/m2 was given in Cycle 1. The dose was increased to 800 mg/m2 in Cycle 2 if the pt had no hematologic or nonhematologic toxicity in Cycle 1 that exceeded predefined levels. Pts received folic acid, vitamin B12 and dexamethasone. Results: This interim safety analysis was planned to occur when 30 pts had completed at least one cycle of pemetrexed at 800 mg/m2. At this point 90 pts were enrolled (67 males, 23 females; mean age 59 yr, range 32–83; 98% had 1 prior chemotherapy regimen, 2% had 2 prior regimens). The pemetrexed dose was increased to 800 mg/m2 for Cycle 2 in 48/79 pts (61%), not adjusted for 13 pts (16%), reduced for 3 pts (4%), and 15 pts (19%) discontinued before Cycle 2. The remaining 11 pts were still on Cycle 1. 12 pts (15%) delayed Cycle 2 due to toxicity in Cycle 1. Pts have completed between 1 and 8 cycles (median, 2). Grade 3/4 toxicity has been reported for 36 pts (40%) and included neutropenia (2 pts, 2%), febrile neutropenia (1 pt, 1%), thrombocytopenia (2 pts, 2%), pneumonia (2 pts, 2%), infection (3 pts, 3%), dyspnea (8 pts, 9%), anemia (6 pts, 7%), diarrhea (2 pts, 2%), fatigue (2 pts, 2%), vomiting (1 pt, 1%) and rash (1 pt, 1%). There have been two deaths due to infections related to study drug toxicity. Conclusions: Following one cycle of pemetrexed at 500 mg/m2 the majority of pts were able to receive and tolerate an increased dose of 800 mg/m2 in Cycle 2, indicating that intrapatient tailoring of pemetrexed dosing in this patient population is feasible and safe. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly AstraZeneca, Eli Lilly Eli Lilly Eli Lilly Eli Lilly, Eli Lilly Korea, SK Pharma Korea