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.
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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 |
Journal | International journal of oncology
(Int J Oncol)
Vol. 34
Issue 6
Pg. 1629-36
(Jun 2009)
ISSN: 1019-6439 [Print] Greece |
PMID | 19424581
(Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acrylamides
- Antibiotics, Antineoplastic
- Iodine Radioisotopes
- N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate
- Doxorubicin
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Topics |
- Acrylamides
(pharmacokinetics, therapeutic use)
- Adult
- Aged
- Antibiotics, Antineoplastic
(pharmacokinetics, therapeutic use)
- Breast Neoplasms
(blood, drug therapy, urine)
- Carcinoma, Non-Small-Cell Lung
(blood, drug therapy, urine)
- Colorectal Neoplasms
(blood, drug therapy, urine)
- Doxorubicin
(pharmacokinetics, therapeutic use)
- Female
- Humans
- Iodine Radioisotopes
- Lung Neoplasms
(blood, drug therapy, urine)
- Male
- Middle Aged
- Prognosis
- Survival Rate
- Tissue Distribution
- Treatment Outcome
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