Two doses of NGR-hTNF in combination with capecitabine plus oxaliplatin in colorectal cancer patients failing standard therapies.

Abstract

BACKGROUND:

asparagine-glycine-arginine-human tumour necrosis factor (NGR-hTNF), an agent selectively damaging the tumour vasculature, showed a biphasic dose-response curve in preclinical models. Previous phase I trials of NGR-hTNF indicated 0.8 and 45 μg/m(2) as optimal biological and maximum-tolerated dose, respectively.

PATIENTS AND METHODS:

Two sequential cohorts of 12 colorectal cancer (CRC) patients who had failed standard therapies received NGR-hTNF 0.8 or 45 μg/m(2) in combination with capecitabine-oxaliplatin (XELOX).

RESULTS:

Median number of prior treatment lines was 3 in the low-dose and 2 in the high-dose cohort. Overall, 21 patients had been pretreated with oxaliplatin-based regimens. No grade 3-4 NGR-hTNF-related toxicities were observed. Grade 1-2 chills were reported in 43% and 40% of cycles in the low-dose and high-dose cohorts, respectively. In the low-dose cohort, one patient achieved a partial response and five had stable disease for a median of 4.6 months. In the high-dose cohort, six patients had stable disease for a median of 3.6 months. Three-month progression-free survival (PFS) rates were 50% and 33% in the low-dose and high-dose cohort, respectively. Three patients in low-dose cohort experienced PFS longer than PFS on last prior therapy.

CONCLUSIONS:

Both NGR-hTNF doses were safely combined with XELOX in pretreated CRC patients. Hint of activity was apparent only with low-dose NGR-hTNF.

• Authors: S Mammoliti, V Andretta, E Bennicelli, F Caprioni, D Comandini, G Fornarini, A Guglielmi, A Pessino, S Sciallero, A F Sobrero, G Mazzola, A Lambiase, C Bordignon
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 22 Issue 4 Pg. 973-978 (Apr 2011) ISSN: 1569-8041 [Electronic] England
• PMID: 20855468 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Chemical References

• Organoplatinum Compounds
• Oxaloacetates
• Recombinant Fusion Proteins
• Tumor Necrosis Factor-alpha
• tumor necrosis factor-alpha, CNGRC fusion protein, human
• Oxaliplatin
• Deoxycytidine
• Capecitabine
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Capecitabine
• Colorectal Neoplasms (drug therapy)
• Deoxycytidine (administration & dosage, analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Dose-Response Relationship, Drug
• Female
• Fluorouracil (administration & dosage, analogs & derivatives, therapeutic use)
• Humans
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage, therapeutic use)
• Oxaliplatin
• Oxaloacetates
• Recombinant Fusion Proteins (administration & dosage, therapeutic use)
• Salvage Therapy
• Treatment Outcome
• Tumor Necrosis Factor-alpha (administration & dosage, therapeutic use)