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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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.
|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|
|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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