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

98 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

Fingerprint

Dive into the research topics of 'Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT)'. Together they form a unique fingerprint.

Cite this