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01-01-2011 | Original Article

Hyaluronan-Irinotecan improves progression-free survival in 5-fluorouracil refractory patients with metastatic colorectal cancer: a randomized phase II trial

Authors: Peter Gibbs, Philip R. Clingan, Vinod Ganju, Andrew H. Strickland, Shirley S. Wong, Niall C. Tebbutt, Craig R. Underhill, Richard M. Fox, Steven P. Clavant, Jenny Leung, Minh Pho, Tracey J. Brown

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2011

Abstract

Purpose

The objective of this study was to conduct a randomised phase II study in second-line metastatic colorectal cancer with the purpose of confirming preliminary clinical data indicating that the formulation of irinotecan with the drug carrier, hyaluronan (HA) reduced toxicity of the drug.

Methods

Irinotecan-naïve patients were randomized to receive either irinotecan (350 mg/m²) or HA-Irinotecan (HA 1,000 mg/m² and irinotecan at 350 mg/m²) every 3 weeks for a maximum of eight cycles.

Results

Seventy-six patients (41 HA-Irinotecan and 35 irinotecan-alone) were enrolled. There was no significant difference in any individual, or overall, grade 3 or 4 toxicity. There was a trend for increased diarrhea in the HA-Irinotecan-treated patients (20 versus 9%; P = 21), potentially explained by a disproportionate number of baseline toxicity-associated risk factors in this treatment group. The median number of cycles completed was six for HA-Irinotecan patients and two for irinotecan-alone patients (P = 0.005). When compared to the control arm, HA-Irinotecan patients had a significantly longer median progression-free survival of 5.2 versus 2.4 months (P = 0.017) and time to treatment failure (4 vs. 1.8 months; P = 0.007). Median overall survival was 10.1 months for HA-Irinotecan compared to 8.0 months for irinotecan patients (P = 0.196).

Conclusion

Further studies are required to define the safety of the formulation of irinotecan with HA. While this study was not adequately powered to demonstrate survival differences, these phase II data indicated HA-Irinotecan to be a promising therapy demonstrating improved efficacy compared to irinotecan-alone.

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Title: Hyaluronan-Irinotecan improves progression-free survival in 5-fluorouracil refractory patients with metastatic colorectal cancer: a randomized phase II trial
Authors: Peter Gibbs
Philip R. Clingan
Vinod Ganju
Andrew H. Strickland
Shirley S. Wong
Niall C. Tebbutt
Craig R. Underhill
Richard M. Fox
Steven P. Clavant
Jenny Leung
Minh Pho
Tracey J. Brown
Publication date: 01-01-2011
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2011
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-010-1303-3

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