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

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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.

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Acknowledgments

The authors are grateful to all the staff at the study centres who contributed to this study.

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Authors and Affiliations

  1. Centre for Oncology and Applied Pharmacology, University of Glasgow, Beatson Laboratories, Garscube Estate, Switchback Road, Glasgow, G61 1BD, UK

    L. C. Scott & T. R. J. Evans

  2. The University of Texas, M.D. Anderson Cancer Centre, 1515 Holcombe Boulevard, Box 426, Houston, TX, 77030, USA

    J. C. Yao & J. A. Ajani

  3. Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, 676 North St Clair, Suite 850, Chicago, IL, 60611, USA

    A. B. Benson III & M. F. Mulcahy

  4. Department of Oncology, Osborne Building, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

    A. L. Thomas

  5. Bristol Haematology and Oncology Centre, Horfield Road, Bristol, BS2 8ED, UK

    S. Falk

  6. Providence Saint Joseph Medical Center, 501 South Buena Vista St, Burnbank, CA, 91505-4866, USA

    R. R. Mena

  7. Washington University School of Medicine, Siteman Cancer Centre, 660 S. Euclid Avenue, Campus Box 8056, St Louis, MO, 63110-1093, USA

    J. Picus

  8. SUNY Upstate Medical Center, 750 East Adams Street, Syracuse, NY, 13210, USA

    J. Wright

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  1. L. C. Scott
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  2. J. C. Yao
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  9. M. F. Mulcahy
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  10. J. A. Ajani
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  11. T. R. J. Evans
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Correspondence to T. R. J. Evans.

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Scott, L.C., Yao, J.C., Benson, A.B. et al. A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma. Cancer Chemother Pharmacol 63, 363–370 (2009). https://doi.org/10.1007/s00280-008-0746-2

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  • DOI: https://doi.org/10.1007/s00280-008-0746-2

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