Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma: A North Central Cancer Treatment Group phase II trial

Steven Robert Alberts, Mark Schroeder, Charles Erlichman, Preston D. Steen, Nathan R. Foster, Dennis F. Moore, Kendrith M. Rowland, Suresh Nair, Loren K. Tschetter, Tom R. Fitch

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Abstract

Purpose: Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study. Methods: Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m2 intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks. Results: Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5% (95% CI, 44.9% to 73.5%) and the median survival was 6.6 months. The response rate was 10.4% (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism. Conclusion: This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered.

Original languageEnglish (US)
Pages (from-to)4944-4950
Number of pages7
JournalJournal of Clinical Oncology
Volume22
Issue number24
DOIs
StatePublished - Dec 15 2004

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gemcitabine
Adenocarcinoma
Neoplasms
Therapeutics
Survival
Pulmonary Embolism
Intravenous Infusions
ISIS 2503
Survival Rate
Radiation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma : A North Central Cancer Treatment Group phase II trial. / Alberts, Steven Robert; Schroeder, Mark; Erlichman, Charles; Steen, Preston D.; Foster, Nathan R.; Moore, Dennis F.; Rowland, Kendrith M.; Nair, Suresh; Tschetter, Loren K.; Fitch, Tom R.

In: Journal of Clinical Oncology, Vol. 22, No. 24, 15.12.2004, p. 4944-4950.

Research output: Contribution to journalArticle

Alberts, SR, Schroeder, M, Erlichman, C, Steen, PD, Foster, NR, Moore, DF, Rowland, KM, Nair, S, Tschetter, LK & Fitch, TR 2004, 'Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma: A North Central Cancer Treatment Group phase II trial', Journal of Clinical Oncology, vol. 22, no. 24, pp. 4944-4950. https://doi.org/10.1200/JCO.2004.05.034
Alberts, Steven Robert ; Schroeder, Mark ; Erlichman, Charles ; Steen, Preston D. ; Foster, Nathan R. ; Moore, Dennis F. ; Rowland, Kendrith M. ; Nair, Suresh ; Tschetter, Loren K. ; Fitch, Tom R. / Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma : A North Central Cancer Treatment Group phase II trial. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 24. pp. 4944-4950.
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title = "Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma: A North Central Cancer Treatment Group phase II trial",
abstract = "Purpose: Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study. Methods: Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m2 intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks. Results: Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5{\%} (95{\%} CI, 44.9{\%} to 73.5{\%}) and the median survival was 6.6 months. The response rate was 10.4{\%} (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism. Conclusion: This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered.",
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T1 - Gemcitabine and ISIS-2503 for patients with locally advanced or metastatic pancreatic adenocarcinoma

T2 - A North Central Cancer Treatment Group phase II trial

AU - Alberts, Steven Robert

AU - Schroeder, Mark

AU - Erlichman, Charles

AU - Steen, Preston D.

AU - Foster, Nathan R.

AU - Moore, Dennis F.

AU - Rowland, Kendrith M.

AU - Nair, Suresh

AU - Tschetter, Loren K.

AU - Fitch, Tom R.

PY - 2004/12/15

Y1 - 2004/12/15

N2 - Purpose: Gemcitabine remains the standard therapy for metastatic pancreatic adenocarcinoma (ACA), but has limited activity. ISIS-2503 is an antisense compound directed against H-ras with preclinical activity against pancreatic ACA in tumor models. The combination of ISIS-2503 and gemcitabine has been evaluated in a prior phase I study. Methods: Patients with metastatic or locally advanced pancreatic ACA not amenable to surgery or local radiation received gemcitabine 1,000 mg/m2 intravenously over 30 minutes on days 1 and 8 and ISIS-2503 6 mg/kg/d as a continuous intravenous infusion over 14 days of an every-3-weeks cycle. Responses were monitored by radiologic imaging every 6 weeks. Results: Forty-eight eligible patients were enrolled, 43 with metastatic disease. Median follow-up was 12.6 months (range, 2.2 to 16.8 months) for living patients. A median of four cycles of treatment was given (range, 1 to 18 cycles). All patients were assessable for response and toxicity. The 6-month survival percentage was 57.5% (95% CI, 44.9% to 73.5%) and the median survival was 6.6 months. The response rate was 10.4% (one complete response, four partial responses). Clinically significant toxicity was limited except for one fatal pulmonary embolism. Conclusion: This study shows a promising response rate to the combination of gemcitabine and ISIS-2503 in patients with pancreatic ACA. The observed 6-month survival rate in these patients met our protocol-defined criteria for success. This regimen is tolerable, but is of unclear benefit. Additional studies evaluating the role of gemcitabine and ISIS-2503 in the treatment of pancreatic ACA should be considered.

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