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, Al B Benson III, A. L. Thomas, S. Falk, R. R. Mena, J. Picus, J. Wright, Mary Frances Mulcahy, J. A. Ajani, T. R.J. Evans

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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.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalCancer Chemotherapy and Pharmacology
Volume63
Issue number2
DOIs
StatePublished - Jan 1 2009

Fingerprint

Camptothecin
irinotecan
Stomach
Adenocarcinoma
Topoisomerase I Inhibitors
Toxicity
Chemotherapy
Poisons
Therapeutics
Stomach Neoplasms
Survival
Tumors
Febrile Neutropenia
Fatigue of materials
Anorexia
pegamotecan
Combination Drug Therapy
Neutropenia
Nausea
Vomiting

Keywords

  • Clinical trial
  • Gastric adenocarcinoma
  • Pegamotecan
  • Phase II

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

Cite this

Scott, L. C. ; Yao, J. C. ; Benson III, Al B ; Thomas, A. L. ; Falk, S. ; Mena, R. R. ; Picus, J. ; Wright, J. ; Mulcahy, Mary Frances ; Ajani, J. A. ; Evans, T. R.J. / A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma. In: Cancer Chemotherapy and Pharmacology. 2009 ; Vol. 63, No. 2. pp. 363-370.
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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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A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma. / Scott, L. C.; Yao, J. C.; Benson III, Al B; Thomas, A. L.; Falk, S.; Mena, R. R.; Picus, J.; Wright, J.; Mulcahy, Mary Frances; Ajani, J. A.; Evans, T. R.J.

In: Cancer Chemotherapy and Pharmacology, Vol. 63, No. 2, 01.01.2009, p. 363-370.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma

AU - Scott, L. C.

AU - Yao, J. C.

AU - Benson III, Al B

AU - Thomas, A. L.

AU - Falk, S.

AU - Mena, R. R.

AU - Picus, J.

AU - Wright, J.

AU - Mulcahy, Mary Frances

AU - Ajani, J. A.

AU - Evans, T. R.J.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

KW - Clinical trial

KW - Gastric adenocarcinoma

KW - Pegamotecan

KW - Phase II

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