Phase II study of asparagine-glycine-arginine-human tumor necrosis factor alpha, a selective vascular targeting agent, in previously treated patients with malignant pleural mesothelioma.

Abstract

PURPOSE:

NGR-hTNF consists of human tumor necrosis factor alpha (hTNF-alpha) fused to the tumor-homing peptide asparagine-glycine-arginine (NGR) able to selectively bind an aminopeptidase N isoform overexpressed on tumor blood vessels. Hypervascularity is a prominent and poor-prognosis feature of malignant pleural mesothelioma (MPM). Currently, there are no standard options for patients with MPM who are failing a front-line pemetrexed-based regimen. We explored safety and efficacy of NGR-hTNF in this setting.

PATIENTS AND METHODS:

Eligible patients had radiologically documented tumor progression and performance status < or = 2. Primary study aim was progression-free survival (PFS). NGR-hTNF 0.8 microg/m(2) was given intravenously every 3 weeks. A subsequent cohort of patients received 0.8 microg/m(2) on a weekly basis.

RESULTS:

In the triweekly cohort (n = 43), only one grade 3 drug-related toxicity was noted, and the most common grades 1 to 2 were short-lived chills (71%). The median PFS was 2.8 months (95% CI, 2.3 to 3.3 months). Nineteen patients (44%) had disease control (one had partial response, and 18 had stable diseases) and experienced a median progression-free time of 4.4 months. In the weekly cohort (n = 14), there was no higher toxicity, and median PFS was 3.0 months (95% CI, 1.9 to 4.1 months). Seven patients (50%) had disease control (all stable diseases) and had a median progression-free interval of 9.1 months. In the overall study population (N = 57), median PFS was 2.8 months. Median progression-free time was 4.7 months in twenty-six patients (46%) who achieved disease control. Median survival was 12.1 months.

CONCLUSION:

The tolerability and disease control of NGR-hTNF 0.8 microg/m(2) weekly warrant additional evaluation in patients with advanced MPM.

• Authors: Vanesa Gregorc, Paolo A Zucali, Armando Santoro, Giovanni L Ceresoli, Giovanni Citterio, Tommaso M De Pas, Nicoletta Zilembo, Fabio De Vincenzo, Matteo Simonelli, Gilda Rossoni, Anna Spreafico, Maria Grazia Viganò, Floriana Fontana, Filippo G De Braud, Emilio Bajetta, Federico Caligaris-Cappio, Paolo Bruzzi, Antonio Lambiase, Claudio Bordignon
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 15 Pg. 2604-11 (May 20 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20406925 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Fusion Proteins
• Tumor Necrosis Factor-alpha
• tumor necrosis factor-alpha, CNGRC fusion protein, human

Topics

• Aged
• Aged, 80 and over
• Cohort Studies
• Disease-Free Survival
• Female
• Humans
• Male
• Mesothelioma (drug therapy, pathology)
• Middle Aged
• Pleural Neoplasms (drug therapy, pathology)
• Recombinant Fusion Proteins (adverse effects, therapeutic use)
• Tumor Necrosis Factor-alpha (adverse effects, therapeutic use)