title: A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma.
abstract: OBJECTIVE
  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.
  
  
  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 < or =2, with adequate haematological, renal and hepatic function, who had received < or =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.
authors.affiliation: Centre for Oncology and Applied Pharmacology, University of Glasgow, Beatson Laboratories, Garscube Estate, Switchback Road, Glasgow G61 1BD, UK.
authors.forename: L C
authors.initials: LC
authors.lastname: Scott
authors.forename: J C
authors.initials: JC
authors.lastname: Yao
authors.forename: A B
authors.initials: AB
authors.lastname: Benson
authors.forename: A L
authors.initials: AL
authors.lastname: Thomas
authors.forename: S
authors.initials: S
authors.lastname: Falk
authors.forename: R R
authors.initials: RR
authors.lastname: Mena
authors.forename: J
authors.initials: J
authors.lastname: Picus
authors.forename: J
authors.initials: J
authors.lastname: Wright
authors.forename: M F
authors.initials: MF
authors.lastname: Mulcahy
authors.forename: J A
authors.initials: JA
authors.lastname: Ajani
authors.forename: T R J
authors.initials: TR
authors.lastname: Evans
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004943:Esophagogastric Junction / Q000473:pathology*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011092:Polyethylene Glycols; C115093:pegamotecan; D002166:Camptothecin