Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer.
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.
Seymour
Leonard W
LW
Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham, UK. len.seymour@clinpharm.ox.ac.uk
Ferry
David R
DR
Kerr
David J
DJ
Rea
Daniel
D
Whitlock
Maggie
M
Poyner
Richard
R
Boivin
Christopher
C
Hesslewood
Stuart
S
Twelves
Christopher
C
Blackie
Robert
R
Schatzlein
Andreas
A
Jodrell
Duncan
D
Bissett
Donald
D
Calvert
Hilary
H
Lind
Mike
M
Robbins
Adele
A
Burtles
Sally
S
Duncan
Ruth
R
Cassidy
James
J
D000178:Acrylamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome
D000178:Acrylamides; D000903:Antibiotics, Antineoplastic; D007457:Iodine Radioisotopes; C482378:N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate; D004317:Doxorubicin