Phase II clinical trial with 5-fluorouracil, recombinant interferon-α-2b, and cisplatin for patients with metastatic or regionally advanced carcinoma of the esophagus

Scott Wadler, Hilda Haynes-Lewis, Jonathan J. Beitler, Xiaoping Hu, Stanley Fell, Margarita Camacho, Barry Levine, Peter H. Wiernik

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

BACKGROUND. Recombinant interferon-α (IFN) augments the cytotoxicity of both 5-fluorouracil (5-FU) and cisplatin in vitro. A Phase II study of 5-FU and IFN resulted in response rates of 25-27% in patients with metastatic esophageal carcinoma. METHODS. A Phase II trial was initiated to determine the clinical utility of a three-drug combination (FIP) in patients with regionally advanced or metastatic esophageal carcinoma. Eligibility included biopsy-proven Stage III or IV squamous cell carcinoma or adenocarcinoma of the esophagus with no prior chemotherapy, adequate performance status, nutritional status, bone marrow, hepatic and renal function, and signed informed consent. Patients were treated in the exact sequence of IFN ⇒ cisplatin ⇒ 5-FU. Patients received 5-FU, 750 mg/m2/day for 5 days followed by weekly bolus therapy at the same dose; cisplatin, 100 mg/m2 on Day 1, followed by weekly therapy, 25 mg/m2 over the course of 1 hour; and IFN, 10 MU subcutaneously 3 times/week beginning on Day 1. All patients received sargramostim (granulocyte-macrophage colony-stimulating factor, Escherichia coli-derived), 5 μg/kg subcutaneously 5 times/week. No patients received radiotherapy. RESULTS. Twenty-four patients were enrolled; 23 were eligible, and 1 was excluded on pathology review (patient was found to have a leiomyoblastoma). The demographics of the population were: median age, 63 years (range, 43-73 years); 18 male patients; squamous cell carcinoma: adenocarcinoma ratio, 22:1; and Stage III:IV ratio, 10:13. Grade 3-4 National Cancer Institute Common Toxicity Criteria toxicities included: leukopenia (13), thrombocytopenia (14), and infection (9). Grade 3 diarrhea, mucositis, and vomiting occurred in 6 patients, 4 patients, and 1 patient, respectively. There were two instances of sudden death, likely related to tumor progression. Major responses occurred in 15 of 23 patients (65%; 95% confidence interval, 43%, 85%) (1 complete response, 14 partial responses). The median survival was 8.6 months; with a median follow-up of 26 months, estimated 30-month survival was 31%. CONCLUSIONS. This regimen, although moderately toxic, has substantial activity in metastatic and regionally advanced squamous cell carcinoma of the esophagus. Further investigations should be conducted to determine the role of IFN in the treatment of esophageal carcinoma.

Original languageEnglish (US)
Pages (from-to)30-34
Number of pages5
JournalCancer
Volume78
Issue number1
DOIs
StatePublished - Jul 1 1996

Fingerprint

Phase II Clinical Trials
Fluorouracil
Interferons
Cisplatin
Esophagus
Carcinoma
Squamous Cell Carcinoma
Epithelioid Leiomyoma
Mucositis
Survival
National Cancer Institute (U.S.)
Poisons
Leukopenia
Drug Combinations
Granulocyte-Macrophage Colony-Stimulating Factor
Sudden Death
Nutritional Status
Informed Consent
Thrombocytopenia
Vomiting

Keywords

  • 5-fluorouracil
  • Biochemical modulation
  • Cisplatin
  • Esophageal carcinoma
  • Interferon

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase II clinical trial with 5-fluorouracil, recombinant interferon-α-2b, and cisplatin for patients with metastatic or regionally advanced carcinoma of the esophagus. / Wadler, Scott; Haynes-Lewis, Hilda; Beitler, Jonathan J.; Hu, Xiaoping; Fell, Stanley; Camacho, Margarita; Levine, Barry; Wiernik, Peter H.

In: Cancer, Vol. 78, No. 1, 01.07.1996, p. 30-34.

Research output: Contribution to journalArticle

Wadler, Scott ; Haynes-Lewis, Hilda ; Beitler, Jonathan J. ; Hu, Xiaoping ; Fell, Stanley ; Camacho, Margarita ; Levine, Barry ; Wiernik, Peter H. / Phase II clinical trial with 5-fluorouracil, recombinant interferon-α-2b, and cisplatin for patients with metastatic or regionally advanced carcinoma of the esophagus. In: Cancer. 1996 ; Vol. 78, No. 1. pp. 30-34.
@article{11172b531996461fb176d18c9bf599eb,
title = "Phase II clinical trial with 5-fluorouracil, recombinant interferon-α-2b, and cisplatin for patients with metastatic or regionally advanced carcinoma of the esophagus",
abstract = "BACKGROUND. Recombinant interferon-α (IFN) augments the cytotoxicity of both 5-fluorouracil (5-FU) and cisplatin in vitro. A Phase II study of 5-FU and IFN resulted in response rates of 25-27{\%} in patients with metastatic esophageal carcinoma. METHODS. A Phase II trial was initiated to determine the clinical utility of a three-drug combination (FIP) in patients with regionally advanced or metastatic esophageal carcinoma. Eligibility included biopsy-proven Stage III or IV squamous cell carcinoma or adenocarcinoma of the esophagus with no prior chemotherapy, adequate performance status, nutritional status, bone marrow, hepatic and renal function, and signed informed consent. Patients were treated in the exact sequence of IFN ⇒ cisplatin ⇒ 5-FU. Patients received 5-FU, 750 mg/m2/day for 5 days followed by weekly bolus therapy at the same dose; cisplatin, 100 mg/m2 on Day 1, followed by weekly therapy, 25 mg/m2 over the course of 1 hour; and IFN, 10 MU subcutaneously 3 times/week beginning on Day 1. All patients received sargramostim (granulocyte-macrophage colony-stimulating factor, Escherichia coli-derived), 5 μg/kg subcutaneously 5 times/week. No patients received radiotherapy. RESULTS. Twenty-four patients were enrolled; 23 were eligible, and 1 was excluded on pathology review (patient was found to have a leiomyoblastoma). The demographics of the population were: median age, 63 years (range, 43-73 years); 18 male patients; squamous cell carcinoma: adenocarcinoma ratio, 22:1; and Stage III:IV ratio, 10:13. Grade 3-4 National Cancer Institute Common Toxicity Criteria toxicities included: leukopenia (13), thrombocytopenia (14), and infection (9). Grade 3 diarrhea, mucositis, and vomiting occurred in 6 patients, 4 patients, and 1 patient, respectively. There were two instances of sudden death, likely related to tumor progression. Major responses occurred in 15 of 23 patients (65{\%}; 95{\%} confidence interval, 43{\%}, 85{\%}) (1 complete response, 14 partial responses). The median survival was 8.6 months; with a median follow-up of 26 months, estimated 30-month survival was 31{\%}. CONCLUSIONS. This regimen, although moderately toxic, has substantial activity in metastatic and regionally advanced squamous cell carcinoma of the esophagus. Further investigations should be conducted to determine the role of IFN in the treatment of esophageal carcinoma.",
keywords = "5-fluorouracil, Biochemical modulation, Cisplatin, Esophageal carcinoma, Interferon",
author = "Scott Wadler and Hilda Haynes-Lewis and Beitler, {Jonathan J.} and Xiaoping Hu and Stanley Fell and Margarita Camacho and Barry Levine and Wiernik, {Peter H.}",
year = "1996",
month = "7",
day = "1",
doi = "10.1002/(SICI)1097-0142(19960701)78:1<30::AID-CNCR6>3.0.CO;2-L",
language = "English (US)",
volume = "78",
pages = "30--34",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

TY - JOUR

T1 - Phase II clinical trial with 5-fluorouracil, recombinant interferon-α-2b, and cisplatin for patients with metastatic or regionally advanced carcinoma of the esophagus

AU - Wadler, Scott

AU - Haynes-Lewis, Hilda

AU - Beitler, Jonathan J.

AU - Hu, Xiaoping

AU - Fell, Stanley

AU - Camacho, Margarita

AU - Levine, Barry

AU - Wiernik, Peter H.

PY - 1996/7/1

Y1 - 1996/7/1

N2 - BACKGROUND. Recombinant interferon-α (IFN) augments the cytotoxicity of both 5-fluorouracil (5-FU) and cisplatin in vitro. A Phase II study of 5-FU and IFN resulted in response rates of 25-27% in patients with metastatic esophageal carcinoma. METHODS. A Phase II trial was initiated to determine the clinical utility of a three-drug combination (FIP) in patients with regionally advanced or metastatic esophageal carcinoma. Eligibility included biopsy-proven Stage III or IV squamous cell carcinoma or adenocarcinoma of the esophagus with no prior chemotherapy, adequate performance status, nutritional status, bone marrow, hepatic and renal function, and signed informed consent. Patients were treated in the exact sequence of IFN ⇒ cisplatin ⇒ 5-FU. Patients received 5-FU, 750 mg/m2/day for 5 days followed by weekly bolus therapy at the same dose; cisplatin, 100 mg/m2 on Day 1, followed by weekly therapy, 25 mg/m2 over the course of 1 hour; and IFN, 10 MU subcutaneously 3 times/week beginning on Day 1. All patients received sargramostim (granulocyte-macrophage colony-stimulating factor, Escherichia coli-derived), 5 μg/kg subcutaneously 5 times/week. No patients received radiotherapy. RESULTS. Twenty-four patients were enrolled; 23 were eligible, and 1 was excluded on pathology review (patient was found to have a leiomyoblastoma). The demographics of the population were: median age, 63 years (range, 43-73 years); 18 male patients; squamous cell carcinoma: adenocarcinoma ratio, 22:1; and Stage III:IV ratio, 10:13. Grade 3-4 National Cancer Institute Common Toxicity Criteria toxicities included: leukopenia (13), thrombocytopenia (14), and infection (9). Grade 3 diarrhea, mucositis, and vomiting occurred in 6 patients, 4 patients, and 1 patient, respectively. There were two instances of sudden death, likely related to tumor progression. Major responses occurred in 15 of 23 patients (65%; 95% confidence interval, 43%, 85%) (1 complete response, 14 partial responses). The median survival was 8.6 months; with a median follow-up of 26 months, estimated 30-month survival was 31%. CONCLUSIONS. This regimen, although moderately toxic, has substantial activity in metastatic and regionally advanced squamous cell carcinoma of the esophagus. Further investigations should be conducted to determine the role of IFN in the treatment of esophageal carcinoma.

AB - BACKGROUND. Recombinant interferon-α (IFN) augments the cytotoxicity of both 5-fluorouracil (5-FU) and cisplatin in vitro. A Phase II study of 5-FU and IFN resulted in response rates of 25-27% in patients with metastatic esophageal carcinoma. METHODS. A Phase II trial was initiated to determine the clinical utility of a three-drug combination (FIP) in patients with regionally advanced or metastatic esophageal carcinoma. Eligibility included biopsy-proven Stage III or IV squamous cell carcinoma or adenocarcinoma of the esophagus with no prior chemotherapy, adequate performance status, nutritional status, bone marrow, hepatic and renal function, and signed informed consent. Patients were treated in the exact sequence of IFN ⇒ cisplatin ⇒ 5-FU. Patients received 5-FU, 750 mg/m2/day for 5 days followed by weekly bolus therapy at the same dose; cisplatin, 100 mg/m2 on Day 1, followed by weekly therapy, 25 mg/m2 over the course of 1 hour; and IFN, 10 MU subcutaneously 3 times/week beginning on Day 1. All patients received sargramostim (granulocyte-macrophage colony-stimulating factor, Escherichia coli-derived), 5 μg/kg subcutaneously 5 times/week. No patients received radiotherapy. RESULTS. Twenty-four patients were enrolled; 23 were eligible, and 1 was excluded on pathology review (patient was found to have a leiomyoblastoma). The demographics of the population were: median age, 63 years (range, 43-73 years); 18 male patients; squamous cell carcinoma: adenocarcinoma ratio, 22:1; and Stage III:IV ratio, 10:13. Grade 3-4 National Cancer Institute Common Toxicity Criteria toxicities included: leukopenia (13), thrombocytopenia (14), and infection (9). Grade 3 diarrhea, mucositis, and vomiting occurred in 6 patients, 4 patients, and 1 patient, respectively. There were two instances of sudden death, likely related to tumor progression. Major responses occurred in 15 of 23 patients (65%; 95% confidence interval, 43%, 85%) (1 complete response, 14 partial responses). The median survival was 8.6 months; with a median follow-up of 26 months, estimated 30-month survival was 31%. CONCLUSIONS. This regimen, although moderately toxic, has substantial activity in metastatic and regionally advanced squamous cell carcinoma of the esophagus. Further investigations should be conducted to determine the role of IFN in the treatment of esophageal carcinoma.

KW - 5-fluorouracil

KW - Biochemical modulation

KW - Cisplatin

KW - Esophageal carcinoma

KW - Interferon

UR - http://www.scopus.com/inward/record.url?scp=0029997118&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029997118&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0142(19960701)78:1<30::AID-CNCR6>3.0.CO;2-L

DO - 10.1002/(SICI)1097-0142(19960701)78:1<30::AID-CNCR6>3.0.CO;2-L

M3 - Article

C2 - 8646722

AN - SCOPUS:0029997118

VL - 78

SP - 30

EP - 34

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 1

ER -