A phase II study of 5-fluorouracil, leucovorin, and interferon-α in the treatment of patients with metastatic or recurrent gastric carcinoma

An Eastern Cooperative Oncology Group study (E5292)

Gary R. Hudes, Stuart Lipsitz, Jean L Grem, Mary Morrisey, Louis Weiner, John W. Kugler, Al Benson

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

BACKGROUND. Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-α (IFN-α) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma. METHODS. Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-α (5 million U/m2 administered subcutaneously daily on Days 1-7), LV (500 mg/m2 administered intravenously over 30 minutes immediately after IFN-α on Days 2-6), and 5-FU (370 mg/m2 given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis. RESULTS. The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5%) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6% and 35.7% of patients, respectively. Other severe (Grade 3- 4) toxicities were granulocytopenia (which occurred in 21.4% of patients) and fatigue (in 10.7%). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5% (95% confidence interval = 2.7-32.4%). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively. CONCLUSIONS. Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma.

Original languageEnglish (US)
Pages (from-to)290-294
Number of pages5
JournalCancer
Volume85
Issue number2
DOIs
StatePublished - Feb 2 1999

Fingerprint

Leucovorin
Fluorouracil
Interferons
Stomach
Carcinoma
Therapeutics
Stomatitis
Agranulocytosis
Cryotherapy
Disease-Free Survival
Fatigue
Colorectal Neoplasms
Diarrhea
Patient Care
Adenocarcinoma
Fever
Confidence Intervals
Drug Therapy

Keywords

  • 5-fluorouracil
  • Chemotherapy
  • Gastric carcinoma
  • Interferon

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A phase II study of 5-fluorouracil, leucovorin, and interferon-α in the treatment of patients with metastatic or recurrent gastric carcinoma : An Eastern Cooperative Oncology Group study (E5292). / Hudes, Gary R.; Lipsitz, Stuart; Grem, Jean L; Morrisey, Mary; Weiner, Louis; Kugler, John W.; Benson, Al.

In: Cancer, Vol. 85, No. 2, 02.02.1999, p. 290-294.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND. Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-α (IFN-α) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma. METHODS. Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-α (5 million U/m2 administered subcutaneously daily on Days 1-7), LV (500 mg/m2 administered intravenously over 30 minutes immediately after IFN-α on Days 2-6), and 5-FU (370 mg/m2 given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis. RESULTS. The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5{\%}) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6{\%} and 35.7{\%} of patients, respectively. Other severe (Grade 3- 4) toxicities were granulocytopenia (which occurred in 21.4{\%} of patients) and fatigue (in 10.7{\%}). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5{\%} (95{\%} confidence interval = 2.7-32.4{\%}). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively. CONCLUSIONS. Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma.",
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AU - Kugler, John W.

AU - Benson, Al

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N2 - BACKGROUND. Chemotherapy has a limited impact on adenocarcinoma of the stomach. Although biochemical modulation of 5-fluorouracil (5-FU) by leucovorin (LV) and interferon-α (IFN-α) has improved the outcomes of patients with metastatic colorectal carcinoma compared with 5-FU alone, this approach has not been extensively evaluated in the treatment of advanced gastric carcinoma. METHODS. Twenty-seven patients with bidimensionally measurable, metastatic gastric carcinoma and an Eastern Cooperative Oncology Group performance status of 0 or 1 received the combination of IFN-α (5 million U/m2 administered subcutaneously daily on Days 1-7), LV (500 mg/m2 administered intravenously over 30 minutes immediately after IFN-α on Days 2-6), and 5-FU (370 mg/m2 given as an intravenous bolus 60 minutes after LV on Days 2-6), with treatment repeated every 4 weeks. Oral cryotherapy was administered routinely before each dose of 5-FU to reduce the incidence of severe stomatitis. RESULTS. The median age of the patients was 58 years (range, 20-76), and 22 patients had residual, unresectable primary lesions. The median number of cycles received was 3 (range, 1-11). Of 24 patients who received at least 2 cycles of treatment, 15 (62.5%) did not require dose reduction for toxicity during the initial 2 cycles. The predominant toxicities were gastrointestinal: diarrhea and stomatitis of Grade 3-4 occurred in 28.6% and 35.7% of patients, respectively. Other severe (Grade 3- 4) toxicities were granulocytopenia (which occurred in 21.4% of patients) and fatigue (in 10.7%). Fever and flu-like symptoms were common but usually mild. Of 24 patients who were evaluable for response, 3 had partial responses (PR) of 16, 23, and 33 weeks' duration, respectively, for a response rate of 12.5% (95% confidence interval = 2.7-32.4%). Two additional patients had reductions in tumor size sufficient for PR, but scans to document the minimum required response duration of 4 weeks were not obtained before progressive disease occurred. The median progression-free and overall survivals were 2.5 and 7.8 months, respectively. CONCLUSIONS. Although this regimen can be administered safely with appropriate supportive care to patients with good performance status, it has limited therapeutic activity in patients with advanced gastric carcinoma.

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