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Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer

Lookup NU author(s): Professor Hilary Calvert

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Abstract

Phase I studies of [N-(2-hydroxypropyl)methacrylamide] (HPMA) copolymer-doxorubicin previously showed signs of activity coupled with 5-fold decreased anthracycline toxicity in chemotherapy-refractory patients. Here we report phase II studies using a similar material (FCE28068) in patients with breast (n=17), non-small cell lung (NSCLC, n=29) and colorectal (n=16) cancer. Up to 8 courses of PK1 (280 mg/m2 doxorubicin-equivalent) were given i.v., together with 123I-labelled imaging analogue. Toxicities were tolerable, with grade 3 neutropenia more prominent in patients with breast cancer (4/17, 23.5% compared with 5/62, 8.1% overall). Of 14 evaluable patients with breast cancer 3 had partial responses (PR), all anthracycline-naïve patients. In 26 evaluable patients with NSCLC, 3 chemotherapy-naïve patients had PR. In contrast, none of the 16 evaluable patients with colorectal cancer responded. Imaging of 16 patients (5 with breast cancer, 6 NSCLC, 5 colorectal cancer) showed obvious tumour accumulation in 2 metastatic breast cancers, although unfortunately no images were obtained from patients who responded. These results show 6/62 PR with limited side effects, supporting the concept that polymer-bound therapeutics can have modified and improved anticancer activities and suggesting the approach should be explored further for breast cancer and NSCLC.


Publication metadata

Author(s): Seymour L, Ferry D, Kerr D, Rea D, Whitlock M, Poyner R, Boivin C, Hesselewood S, Twelves C, Blackie R, Schatzlein A, Jodrell D, Bissett D, Calvert H, Lind M, Robbins A, Burtles S, Duncan R, Cassidy J

Publication type: Article

Publication status: Published

Journal: International Journal of Oncology

Year: 2009

Volume: 34

Issue: 6

Pages: 1629-1636

ISSN (print): 1019-6439

ISSN (electronic): 1791-2423

Publisher: Spandidos Publications

URL: http://dx.doi.org/10.3892/ijo_00000293

DOI: 10.3892/ijo_00000293

PubMed id: 19424581


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