A Phase II trial of Denileukin Diftitox in patients with previously treated advanced non-small cell lung cancer.
BACKGROUND
Denileukin diftitox, a chimeric protein, uses the cytocidal properties of diphtheria toxin to cells expressing interleukin-2 receptors. The aim of this study was to evaluate the efficacy and safety of denileukin diftitox in the treatment of advanced relapsed nonsmall cell lung cancer (NSCLC).


METHODS
Multicenter phase II trial in patients with NSCLC with Eastern Cooperative Oncology Group PS 0-2, stage IIIB/IV at diagnosis, who had failed at least 1 previous chemotherapy regimen. Denileukin diftitox was infused at 18 microg/kg/d x 5 days, every 21 days for 6 cycles.


RESULTS
For the 41 patients enrolled, the median age was 56 years (range, 21-80), 25 were men, and the median number of previous chemotherapy regimens was 2 (range, 1-5). The median number of treatment cycles was 2 (range, 1-6). By RECIST criteria, 18 (44%) had stable disease, 10 (24%) progressive disease, and 13 (32%) were not evaluable for response as they received less than 2 treatment cycles. The median time to disease progression was 1.8 months [range, 0.3-11.3; 95% confidence interval (CI) 1.3-2.6]. Median survival was 5.8 months (range, 0.3-33.6; 95% CI 3.4-11.4). The median follow-up time was 16.1 month. One death from myocarditis verified at autopsy was attributed to treatment. One grade 4 toxicity (vascular leak syndrome) was encountered, and 18 grade 3 toxicities, primarily gastro-intestinal, vascular leak syndrome, and constitutional symptoms.


CONCLUSIONS
Denileukin diftitox at current dose schedule has limited activity in patients with previously treated NSCLC, manifested by disease control without impact on survival.
University of Cincinnati, OH, USA.
Margie
M
Gerena-Lewis
Jeffrey
J
Crawford
Philip
P
Bonomi
Ann Marie
AM
Maddox
John
J
Hainsworth
David E
DE
McCune
Rakesh
R
Shukla
Haoyue
H
Zeigler
Paul
P
Hurtubise
Tracy R
TR
Chowdhury
Brandon
B
Fletcher
Karyn
K
Dyehouse
Richard
R
Ghalie
Abdul R
AR
Jazieh
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004167:Diphtheria Toxin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox