Double blind, placebo controlled trial of oral lactoferrin in combination therapy for first line non-small cell lung cancer (NSCLC)

Abstract

7141 Background: Recombinant human lactoferrin (rhLF) is a novel immunostimulatory agent with demonstrated anti-cancer activity in animals and NSCLC patients in Phase I/II trials. Oral rhLF has been administered to over 350 people and appears safe and well tolerated. We evaluated oral rhLF in combination with standard chemotherapy in first line NSCLC patients in this trial. Methods: 110 chemo-naive patients with advanced or metastatic NSCLC from eleven cancer centers were randomized to receive standard therapy (carboplatin + paclitaxel; C/P) plus either rhLF or placebo. C/P was administered in 3-week cycles. RhLF (or placebo) was administered orally, 1.5 g B.I.D., in 35-day cycles until radiological progression for a maximum of three cycles, starting the day following C/P dosing in cycles 1, 3 and 5. The primary end point is Best Overall Response (BOR) by CT using RECIST criteria. Secondary end points include Progression Free Survival (PFS) and Overall Survival by Kaplan-Meier curves and Quality of Life Assessments (EORTC QLQ C30, QLC LC 13) at Weeks 0, 6, 12, 18. Data will be unblinded for preliminary analysis in February 2005. Results: All 110 patients have been enrolled for over ten weeks. Study drug appears to be safe and well tolerated, with only one Grade 3/4 toxicity (abdominal pain) that is possibly rhLF/placebo related. 100 patients have had at least one post-therapy CT, and are evaluable for response rate (RR). So far, there have been 37 (37%) partial responses (PR) and an additional 53 patients (53%) had stable disease on their 6-week CT or later. Median PFS has not been reached. The five major published randomized trials evaluating 3-weekly first line C/P in Stage IIIB/IV NSCLC report an average RR of 25.9%. The 37% blended response rate observed in this trial is significantly better than that expected in this patient population. Conclusions: Oral rhLF is a safe and well-tolerated immunostimulatory drug. If the response rate of placebo patients in this study is consistent with the published literature, the blinded data suggests that rhLF may significantly enhance the response to first line C/P chemotherapy in advanced NSCLC without increasing toxicity. We will present unblinded data at ASCO. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Agennix