PD3-1-8: Motexafin Gadolinium (MGd) is active as a single agent in advanced non-small-cell lung cancer (NSCLC) patients who failed platinum-based chemotherapy: preliminary results of a phase II trial

Ronald B. Natale, Garth Nicholas, Frank Greco, Ramaswamy Govindan, Pierre Chabot, Kishan Pandya, Lane Eubank, Markus F. Renschler
2007 Journal of Thoracic Oncology  
Motexafin gadolinium (MGd) is a tumor-selective antineoplastic agent that disrupts redox dependent pathways by targeting oxidative stress-related proteins such as thioredoxin reductase (TRX). TRX often is overexpressed in NSCLC and is associated with a poor prognosis. Inhibition of TRX reverses tumor phenotype in lung carcinoma cells in vitro and in vivo. This randomized 2-stage phase II trial investigated tumor response and survival with 2 regimens of single agent MGd for the 2nd line
more » ... of advanced NSCLC. Methods: Patients with locally advanced or metastatic NSCLC ± brain metastases, ECOG PS 0-1, who had received one prior platinum-based chemotherapy regimen ± kinase inhibitor were randomized to intravenous MGd (10 mg/kg/week -Group A) or MGd (15 mg/kg/q 3 weeks -Group B) given in 21 day cycles. The sample size was 30 per arm in stage 1, and 24 per arm in stage 2. Response was evaluated by RECIST every 6 weeks. Results: 56 evaluable patients, median age of 62 years (range 41-85), with locally advanced (16%) or metastatic (84%) adenocarcinoma (46%), squamous cell carcinoma (16%), large cell carcinoma (9%), bronchoalveolar carcinoma (4%) or other NSCLC (25%) were randomized to group A (N=26) or group B (N=30). 38% had not responded to first line chemotherapy. MGd treatment was well tolerated, with 1-12 cycles (median 2, mean 3) administered. The most common MGd related grade 3+ adverse events were hypophosphatemia (17.9%), fatigue (12.5%), finger blisters (5.4%) and rash (5.4%). 53 patients were evaluable for response, with a response rate of 5.7% (3 PR, 2 in Group A, 1 in Group B), and 37.7% stable disease. Median time to progression was 12 weeks with 41% free from progression > 1 year. Median survival of 56 evaluable patients was 10.2 months (95% CI: 6.7 months -not reached), with 1-year survival of 44%. Median survival for Group A is not reached at > 14 months, and 9.2 months for Group B. Conclusions: MGd appears active as a single agent for second line treatment of NSCLC patients with advanced or metastatic NSCLC who have failed prior platinum-based chemotherapy, with a response rate comparable to other approved agents, promising survival, and a favorable safety profile. The trial has met the criteria for continuation into stage 2 for each treatment group. PD3-2-1 Molecular Targeted Therapy: EGFR inhibitors, Thu, 12:30 -14:15 Pharmacokinetics of gefitinib predicts the antitumor activity for advanced non-small cell lung cancer (NSCLC)
doi:10.1097/01.jto.0000283402.21334.01 fatcat:xw423mn6fbha5mbovnj625padu