Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-α in patients with advanced pancreatic cancer

Eastern cooperative oncology group protocol 3292

Joseph A. Sparano*, Stuart Lipsitz, Scott Wadler, Richard Hansen, Peter W. Bushunow, John Kirkwood, Patrick J. Flynn, Janice P. Dutcher, Al B. Benson

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Evidence suggests that interferon-α (IFN-α) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-α in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-α (5 x 106 IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-α has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.

Original languageEnglish (US)
Pages (from-to)546-551
Number of pages6
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume19
Issue number6
DOIs
StatePublished - Nov 26 1996

Fingerprint

Pancreatic Neoplasms
Fluorouracil
Interferons
Aspartate Aminotransferases
L-Lactate Dehydrogenase
Adenocarcinoma
Serum
Neoplasm Metastasis
Liver
Antineoplastic Agents
Pancreas
Colorectal Neoplasms
Therapeutics
Confidence Intervals
Cell Line

Keywords

  • 5-Fluorouracil
  • Continuous infusion
  • Interferon-α
  • Pancreatic cancer
  • Therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sparano, Joseph A. ; Lipsitz, Stuart ; Wadler, Scott ; Hansen, Richard ; Bushunow, Peter W. ; Kirkwood, John ; Flynn, Patrick J. ; Dutcher, Janice P. ; Benson, Al B. / Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-α in patients with advanced pancreatic cancer : Eastern cooperative oncology group protocol 3292. In: American Journal of Clinical Oncology: Cancer Clinical Trials. 1996 ; Vol. 19, No. 6. pp. 546-551.
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title = "Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-α in patients with advanced pancreatic cancer: Eastern cooperative oncology group protocol 3292",
abstract = "Evidence suggests that interferon-α (IFN-α) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-α in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-α (5 x 106 IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8{\%}; 95{\%} confidence interval, 0-19{\%}). The majority of the study group (88{\%}) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-α has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.",
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Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-α in patients with advanced pancreatic cancer : Eastern cooperative oncology group protocol 3292. / Sparano, Joseph A.; Lipsitz, Stuart; Wadler, Scott; Hansen, Richard; Bushunow, Peter W.; Kirkwood, John; Flynn, Patrick J.; Dutcher, Janice P.; Benson, Al B.

In: American Journal of Clinical Oncology: Cancer Clinical Trials, Vol. 19, No. 6, 26.11.1996, p. 546-551.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-α in patients with advanced pancreatic cancer

T2 - Eastern cooperative oncology group protocol 3292

AU - Sparano, Joseph A.

AU - Lipsitz, Stuart

AU - Wadler, Scott

AU - Hansen, Richard

AU - Bushunow, Peter W.

AU - Kirkwood, John

AU - Flynn, Patrick J.

AU - Dutcher, Janice P.

AU - Benson, Al B.

PY - 1996/11/26

Y1 - 1996/11/26

N2 - Evidence suggests that interferon-α (IFN-α) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-α in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-α (5 x 106 IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-α has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.

AB - Evidence suggests that interferon-α (IFN-α) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-α in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-α (5 x 106 IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-α has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.

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