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

TitlePhase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer.
Publication TypeJournal Article
Year of Publication2009
AuthorsSeymour LW, Ferry DR, Kerr DJ, Rea D, Whitlock M, Poyner R, Boivin C, Hesslewood S, Twelves C, Blackie R, Schätzlein A, Jodrell D, Bissett D, Calvert H, Lind M, Robbins A, Burtles S, Duncan R, Cassidy J
JournalInt J Oncol
Date Published2009 Jun
KeywordsAcrylamides, Adult, Aged, Antibiotics, Antineoplastic, Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Doxorubicin, Female, Humans, Iodine Radioisotopes, Lung Neoplasms, Male, Middle Aged, Prognosis, Survival Rate, Tissue Distribution, Treatment Outcome

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.

Alternate JournalInt. J. Oncol.
PubMed ID19424581
Grant List11339 / / Cancer Research UK / United Kingdom
/ / Cancer Research UK / United Kingdom