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

Seymour, L.W., Ferry, D.R., Kerr, D.J., Rea, D., Whitlock, M., Poyner, R., Boivin, C., Hesslewood, S., Twelves, C., Blackie, R., Schatzlein, A.G., Jodrell, D.I., Bissett, D., Calvert, H., Lind, M., Robbins, A., Burtles, S., Duncan, R. and Cassidy, J. (2009) Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer. International Journal of Oncology, 34 (6). pp. 1629-1636. 10.3892/ijo_00000293 .

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DOI: 10.3892/ijo_00000293

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/m(2) 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.

Item Type:Article
Uncontrolled Keywords:drug targeting EPR effect; [N-(2-hydroxypropyl)methacrylamide] copolymer conjugates; polymeric produgs
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2313
Journal or Publication Title:International Journal of Oncology
Deposited By:Library Staff
Deposited On:07 Oct 2011 17:34
Last Modified:07 Oct 2011 17:34

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