Phase I dose-escalation study of oral vinorelbine (VRLO) plus pemetrexed (PEM) in patients (pts) with advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC).

Abstract

e18044 Background: PEM and VRLO have shown high activity and good safety profile when given as single agent chemotherapy for NSCLC. Platinum combinations are considered the standard of care of first-line advanced NSCLC treatment. However, some patients cannot receive platinum salts, being treated with non-platinum combinations as an alternative treatment option. PEM is indicated for the 1st-line treatment of patients with locally advanced or metastatic NSCLC other than predominantly squamous cell histology. VRLO is indicated for stage III-IV NSCLC and has shown efficacy in all histology subgroups. Their combination could offer a treatment option in non-squamous 1st-line NSCLC. Methods: A phase I study is being conducted to determine the maximal tolerated dose (MTD) of PEM on day 1 plus VRLO given on days 1 and 8, with 3-weeks cycles as 1st-line treatment in locally advanced or metastatic non-squamous NSCLC pts. Results: As of Jan-2012, 18 pts (M/F: 13/5, median age 61, all PS 0-1) had received 104 cycles in 4 dose levels (DL): VRLO (mg/m2)/PEM (mg/m2): 60/500 (5 pts, DL1), 70/500 (7 pts, DL2), 60-80/500 (3 pts, DL3), 80/500 (3 pt-DL4). Safety: dose limiting toxicity as defined per protocol was neutropenia gr 4 with febrile neutropenia at DL2. Other toxicities were: neutropenia gr 3 (3 pts), gr 2 (2 pts); leukopenia gr 2 (3 pts). Other adverse events included: vomiting (gr 3 / 1 pt) (gr 2 / 5 pts); gr 2 asthenia (5 pts); constipation (gr 2 / 1 pt) (gr 1 / 2 pts); diarrhea (gr 1 /3 pts); fever (gr 1/1 pt); alopecia (gr 1/ 1 pt). Efficacy in 15 evaluable pts: CR, 0 pts; PR, 9 pts; NC, 3 pts; PD, 2 pts. Overall response rate, 60% (73% clinical benefit). Conclusions: The administration of PEM plus VRLO is feasible, the MTD being reached at 80/500 mg/m2. Further exploration of the combination will be planned after final analysis.