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

  • Authors:
    • Leonard W. Seymour
    • David R. Ferry
    • David J. Kerr
    • Daniel Rea
    • Maggie Whitlock
    • Richard Poyner
    • Christopher Boivin
    • Stuart Hesslewood
    • Christopher Twelves
    • Robert Blackie
    • Andreas Schatzlein
    • Duncan Jodrell
    • Donald Bissett
    • Hilary Calvert
    • Mike Lind
    • Adele Robbins
    • Sally Burtles
    • Ruth Duncan
    • James Cassidy
  • Corresponding author:
  • View Affiliations

  • Published online on: Monday, June 1, 2009
  • Pages: 1629-1636 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/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.
Journal Cover

June 2009
Volume 34 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2014 Impact Factor: 3.025
Ranked #30/211 Oncology
(total number of cites)

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APA
Seymour, L.W., Ferry, D.R., Kerr, D.J., Rea, D., Whitlock, M., Poyner, R. ... 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, 1629-1636. http://dx.doi.org/10.3892/ijo_00000293
MLA
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., Jodrell, D., Bissett, D., Calvert, H., Lind, M., Robbins, A., Burtles, S., Duncan, R., Cassidy, J."Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer". International Journal of Oncology 34.6 (2009): 1629-1636.
Chicago
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., Jodrell, D., Bissett, D., Calvert, H., Lind, M., Robbins, A., Burtles, S., Duncan, R., Cassidy, J."Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer". International Journal of Oncology 34, no. 6 (2009): 1629-1636. http://dx.doi.org/10.3892/ijo_00000293