Cancer Chemotherapy and Pharmacology

, Volume 63, Issue 2, pp 363–370

A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma

  • L. C. Scott
  • J. C. Yao
  • A. B. BensonIII
  • A. L. Thomas
  • S. Falk
  • R. R. Mena
  • J. Picus
  • J. Wright
  • M. F. Mulcahy
  • J. A. Ajani
  • T. R. J. Evans
Original Article

DOI: 10.1007/s00280-008-0746-2

Cite this article as:
Scott, L.C., Yao, J.C., Benson, A.B. et al. Cancer Chemother Pharmacol (2009) 63: 363. doi:10.1007/s00280-008-0746-2

Abstract

Purpose

Combination chemotherapy results in a significant survival advantage in patients with advanced gastric cancer compared to best supportive care. Nevertheless, the prognosis remains poor with a median survival of 8–10 months. Topoisomerase-I inhibitors such as irinotecan have activity in advanced gastric cancer. Pegamotecan may offer significant advantages over other topoisomerase-I inhibitors due to its prolonged circulating half-life, tolerability and passive tumour accumulation.

Patients and methods

This was a non-randomised, multi-centre, two-step Fleming design phase II study. Eligible patients with locally advanced (inoperable) or metastatic gastric or gastro-oesophageal adenocarcinoma, with measurable disease, ECOG performance status ≤2, with adequate haematological, renal and hepatic function, who had received ≤1 prior chemotherapy regimen for advanced disease, were treated with 7,000 mg/m2 of pegamotecan as a 1-h infusion every 21 days until disease progression or unacceptable toxicity. The primary efficacy measure was the objective response rate.

Results

Five of the 35 patients recruited into this study had a partial response (14.3%), with a median time to progression of 11.9 weeks (95% CI: 6.6, 13.1), and median overall survival of 38.1 weeks (95% CI: 29.0, 47.3). Grade 3/4 toxicities included neutropenia in 6 (17.1%) patients, thrombocytopenia in 4 (11.4%), fatigue in 8 (22.9%), nausea in 6 (17%), vomiting in 6 (17%) and anorexia in 4 (11.4%) patients. There were no episodes of febrile neutropenia and no toxic deaths.

Conclusions

Pegamotecan has activity in this patient population and was generally well-tolerated. The favourable rate of haematological toxicities and diarrhoea compared with irinotecan in similar studies suggests that pegamotecan could be combined with other active agents in further studies in this disease.

Keywords

PegamotecanGastric adenocarcinomaPhase IIClinical trial

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • L. C. Scott
    • 1
  • J. C. Yao
    • 2
  • A. B. BensonIII
    • 3
  • A. L. Thomas
    • 4
  • S. Falk
    • 5
  • R. R. Mena
    • 6
  • J. Picus
    • 7
  • J. Wright
    • 8
  • M. F. Mulcahy
    • 3
  • J. A. Ajani
    • 2
  • T. R. J. Evans
    • 1
  1. 1.Centre for Oncology and Applied PharmacologyUniversity of Glasgow, Beatson LaboratoriesGlasgowUK
  2. 2.The University of Texas, M.D. Anderson Cancer CentreHoustonUSA
  3. 3.Division of Hematology/OncologyNorthwestern University Feinberg School of MedicineChicagoUSA
  4. 4.Department of Oncology, Osborne BuildingLeicester Royal InfirmaryLeicesterUK
  5. 5.Bristol Haematology and Oncology CentreBristolUK
  6. 6.Providence Saint Joseph Medical CenterBurnbankUSA
  7. 7.Washington University School of MedicineSiteman Cancer CentreSt LouisUSA
  8. 8.SUNY Upstate Medical CenterSyracuseUSA