Scott, L. et al. (2009) A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma. Cancer Chemotherapy and Pharmacology, 63(2), pp. 363-370. (doi: 10.1007/s00280-008-0746-2)
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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/m(2) 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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Evans, Professor Jeff |
| Authors: | Scott, L., Yao, J., Benson, A., Thomas, A., Falk, S., Mena, R., Picus, J., Wright, J., Mulcahy, M., Ajani, J., and Evans, T. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Cancer Chemotherapy and Pharmacology |
| ISSN: | 0344-5704 |
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