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

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103 Citations (Scopus)


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
Publication statusPublished - 2004


  • polymeric
  • camptothecin
  • pharmacokinetics
  • NSC-100880


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