Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT)

D Bissett, J Cassidy, J S de Bono, F Muirhead, M Main, L Robson, D Fraier, M L Magne, C Pellizzoni, M G Porro, R Spinelli, W Speed, C Twelves

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

Polymeric cytotoxic conjugates are being developed with the aim of preferential delivery of the anticancer agent to tumour. MAG-CPT comprises the topoisomerase I inhibitor camptothecin linked to a water-soluble polymeric backbone methacryloylglycynamide ( average molecular weight 18 kDa, 10% CPT by weight). It was administered as a 30-min infusion once every 4 weeks to patients with advanced solid malignancies. The objectives of our study were to determine the maximum tolerated dose, dose-limiting toxicities, and the plasma and urine pharmacokinetics of MAG-CPT, and to document responses to this treatment. The starting dose was 30 mgm(-2) (dose expressed as mg equivalent camptothecin). In total, 23 patients received 47 courses at six dose levels, with a maximum dose of 240 mgm(-2). Dose-limiting toxicities were myelosuppression, neutropaenic sepsis, and diarrhoea. One patient died after cycle 1 MAG-CPT at the maximum dose. The maximum tolerated dose and dose recommended for further clinical study was 200 mgm(-2). The half-lives of both MAG-CPT and released CPT were prolonged (46 days) and measurable levels of MAG-CPT were retrieved from plasma and urine 4 weeks after treatment. However, subsequent pharmacodynamic studies of this agent have led to its withdrawal from clinical development.

Original languageEnglish
Pages (from-to)50-55
Number of pages6
JournalBritish Journal of Cancer
Volume91
DOIs
Publication statusPublished - 2004

Keywords

  • MAG-CPT
  • polymeric
  • camptothecin
  • pharmacokinetics
  • POLYETHYLENE-GLYCOL
  • BOUND CAMPTOTHECIN
  • DELIVERY-SYSTEMS
  • ACCUMULATION
  • CONJUGATION
  • NSC-100880

Cite this

Bissett, D., Cassidy, J., de Bono, J. S., Muirhead, F., Main, M., Robson, L., ... Twelves, C. (2004). Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT). British Journal of Cancer, 91, 50-55. https://doi.org/10.1038/sj.bjc.6601922

Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT). / Bissett, D ; Cassidy, J ; de Bono, J S ; Muirhead, F ; Main, M ; Robson, L ; Fraier, D ; Magne, M L ; Pellizzoni, C ; Porro, M G ; Spinelli, R ; Speed, W ; Twelves, C .

In: British Journal of Cancer, Vol. 91, 2004, p. 50-55.

Research output: Contribution to journalArticle

Bissett, D, Cassidy, J, de Bono, JS, Muirhead, F, Main, M, Robson, L, Fraier, D, Magne, ML, Pellizzoni, C, Porro, MG, Spinelli, R, Speed, W & Twelves, C 2004, 'Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT)', British Journal of Cancer, vol. 91, pp. 50-55. https://doi.org/10.1038/sj.bjc.6601922
Bissett, D ; Cassidy, J ; de Bono, J S ; Muirhead, F ; Main, M ; Robson, L ; Fraier, D ; Magne, M L ; Pellizzoni, C ; Porro, M G ; Spinelli, R ; Speed, W ; Twelves, C . / Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT). In: British Journal of Cancer. 2004 ; Vol. 91. pp. 50-55.
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