Phase I-II study of 5-fluorouracil, recombinant interferon α2a, and cisplatin in combination with external beam radiation therapy followed by surgery in patients with locally advanced carcinoma of the esophagus

Snehal Damle, Jonathan J. Beitler, Hilda Haynes-Lewis, Margarita Camacho, Ellen Wolf, Scott Wadler

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Multimodality therapy has been demonstrated to be superior to external beam radiation therapy and possibly surgery alone for the treatment of carcinoma of the esophagus. The combination of 5-fluorouracil (5-FU), cisplatin, and recombinant interferon α2a (IFN) has yielded 65% response rates in metastatic and regionally advanced carcinoma of the esophagus. A phase I-II study was performed to assess the feasibility of combining 5-FU, IFN, and cisplatin with external beam radiation therapy followed by surgery in potentially resectable patients. Eligibility included biopsy-proven stage II-III squamous cell or adenocarcinoma of the esophagus with no prior therapy. External beam radiation therapy was administered concurrently with chemotherapy beginning on day 1, 5 days per week, twice a day with 1.5 Gy/fraction to a total dose of 45 Gy. 5-FU was administered at 750 mg/m2 on days 1, 8, 15, 22, and 29 after the administration of IFN and cisplatin. IFN was given at a dose of 6 million units subcutaneously three times per week beginning on day 1. Dose levels I, II, and III of cisplatin were 25, 30, and 35 mg/m2 administered on days 1, 8, 15, 22, and 29. The sequence of administration was IFN followed by cisplatin followed immediately by 5-FU. Dose escalation between patient cohorts occurred if 0/3 or ≤ 1/6 patients had dose-limiting toxicity, i.e., grade II-III toxicity attributable to cisplatin. A phase II trial was planned using the maximum tolerated dose of cisplatin determined from the phase I trial. Patients who successfully completed therapy underwent thoracic exploration to resect residual disease. Twelve patients were enrolled; all were eligible. The demographics of the population were median age, 60 years (range, 44-77); nine male and three female patients; nine squamous cell carcinoma, one adenocarcinoma, and two adenosquamous histology; stage II:III, 2:10. Grade 3-4 toxicities included granulocytopenia (12 patients), thrombocytopenia (six), anemia (three), infection (six), diarrhea (two), mucositis (two), and renal and hepatic toxicities (one). Five patients had a clinical complete response, among whom four underwent surgery. At surgery, one patient had no evidence of residual disease and three patients had microscopic disease only. Two patients had progressive disease and five could not complete the therapy because of toxicities. Two patients are alive and disease free at 25 and 23 months, respectively. This regimen, though active, demonstrated an unfavorable toxicity profile and cannot be recommended for further study.

Original languageEnglish (US)
Pages (from-to)391-395
Number of pages5
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume22
Issue number4
DOIs
StatePublished - Aug 1 1999

Fingerprint

Fluorouracil
Interferons
Cisplatin
Esophagus
Radiotherapy
Carcinoma
Therapeutics
Mucositis
Agranulocytosis
Maximum Tolerated Dose
Thrombocytopenia
Anemia
Squamous Cell Carcinoma
Diarrhea
Histology
Adenocarcinoma
Thorax
Epithelial Cells
Demography
Kidney

Keywords

  • Esophageal carcinoma
  • Interferon α2a
  • Multimodality therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{27532125ca8744e089b32d0140bca102,
title = "Phase I-II study of 5-fluorouracil, recombinant interferon α2a, and cisplatin in combination with external beam radiation therapy followed by surgery in patients with locally advanced carcinoma of the esophagus",
abstract = "Multimodality therapy has been demonstrated to be superior to external beam radiation therapy and possibly surgery alone for the treatment of carcinoma of the esophagus. The combination of 5-fluorouracil (5-FU), cisplatin, and recombinant interferon α2a (IFN) has yielded 65{\%} response rates in metastatic and regionally advanced carcinoma of the esophagus. A phase I-II study was performed to assess the feasibility of combining 5-FU, IFN, and cisplatin with external beam radiation therapy followed by surgery in potentially resectable patients. Eligibility included biopsy-proven stage II-III squamous cell or adenocarcinoma of the esophagus with no prior therapy. External beam radiation therapy was administered concurrently with chemotherapy beginning on day 1, 5 days per week, twice a day with 1.5 Gy/fraction to a total dose of 45 Gy. 5-FU was administered at 750 mg/m2 on days 1, 8, 15, 22, and 29 after the administration of IFN and cisplatin. IFN was given at a dose of 6 million units subcutaneously three times per week beginning on day 1. Dose levels I, II, and III of cisplatin were 25, 30, and 35 mg/m2 administered on days 1, 8, 15, 22, and 29. The sequence of administration was IFN followed by cisplatin followed immediately by 5-FU. Dose escalation between patient cohorts occurred if 0/3 or ≤ 1/6 patients had dose-limiting toxicity, i.e., grade II-III toxicity attributable to cisplatin. A phase II trial was planned using the maximum tolerated dose of cisplatin determined from the phase I trial. Patients who successfully completed therapy underwent thoracic exploration to resect residual disease. Twelve patients were enrolled; all were eligible. The demographics of the population were median age, 60 years (range, 44-77); nine male and three female patients; nine squamous cell carcinoma, one adenocarcinoma, and two adenosquamous histology; stage II:III, 2:10. Grade 3-4 toxicities included granulocytopenia (12 patients), thrombocytopenia (six), anemia (three), infection (six), diarrhea (two), mucositis (two), and renal and hepatic toxicities (one). Five patients had a clinical complete response, among whom four underwent surgery. At surgery, one patient had no evidence of residual disease and three patients had microscopic disease only. Two patients had progressive disease and five could not complete the therapy because of toxicities. Two patients are alive and disease free at 25 and 23 months, respectively. This regimen, though active, demonstrated an unfavorable toxicity profile and cannot be recommended for further study.",
keywords = "Esophageal carcinoma, Interferon α2a, Multimodality therapy",
author = "Snehal Damle and Beitler, {Jonathan J.} and Hilda Haynes-Lewis and Margarita Camacho and Ellen Wolf and Scott Wadler",
year = "1999",
month = "8",
day = "1",
doi = "10.1097/00000421-199908000-00014",
language = "English (US)",
volume = "22",
pages = "391--395",
journal = "American Journal of Clinical Oncology",
issn = "0277-3732",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Phase I-II study of 5-fluorouracil, recombinant interferon α2a, and cisplatin in combination with external beam radiation therapy followed by surgery in patients with locally advanced carcinoma of the esophagus

AU - Damle, Snehal

AU - Beitler, Jonathan J.

AU - Haynes-Lewis, Hilda

AU - Camacho, Margarita

AU - Wolf, Ellen

AU - Wadler, Scott

PY - 1999/8/1

Y1 - 1999/8/1

N2 - Multimodality therapy has been demonstrated to be superior to external beam radiation therapy and possibly surgery alone for the treatment of carcinoma of the esophagus. The combination of 5-fluorouracil (5-FU), cisplatin, and recombinant interferon α2a (IFN) has yielded 65% response rates in metastatic and regionally advanced carcinoma of the esophagus. A phase I-II study was performed to assess the feasibility of combining 5-FU, IFN, and cisplatin with external beam radiation therapy followed by surgery in potentially resectable patients. Eligibility included biopsy-proven stage II-III squamous cell or adenocarcinoma of the esophagus with no prior therapy. External beam radiation therapy was administered concurrently with chemotherapy beginning on day 1, 5 days per week, twice a day with 1.5 Gy/fraction to a total dose of 45 Gy. 5-FU was administered at 750 mg/m2 on days 1, 8, 15, 22, and 29 after the administration of IFN and cisplatin. IFN was given at a dose of 6 million units subcutaneously three times per week beginning on day 1. Dose levels I, II, and III of cisplatin were 25, 30, and 35 mg/m2 administered on days 1, 8, 15, 22, and 29. The sequence of administration was IFN followed by cisplatin followed immediately by 5-FU. Dose escalation between patient cohorts occurred if 0/3 or ≤ 1/6 patients had dose-limiting toxicity, i.e., grade II-III toxicity attributable to cisplatin. A phase II trial was planned using the maximum tolerated dose of cisplatin determined from the phase I trial. Patients who successfully completed therapy underwent thoracic exploration to resect residual disease. Twelve patients were enrolled; all were eligible. The demographics of the population were median age, 60 years (range, 44-77); nine male and three female patients; nine squamous cell carcinoma, one adenocarcinoma, and two adenosquamous histology; stage II:III, 2:10. Grade 3-4 toxicities included granulocytopenia (12 patients), thrombocytopenia (six), anemia (three), infection (six), diarrhea (two), mucositis (two), and renal and hepatic toxicities (one). Five patients had a clinical complete response, among whom four underwent surgery. At surgery, one patient had no evidence of residual disease and three patients had microscopic disease only. Two patients had progressive disease and five could not complete the therapy because of toxicities. Two patients are alive and disease free at 25 and 23 months, respectively. This regimen, though active, demonstrated an unfavorable toxicity profile and cannot be recommended for further study.

AB - Multimodality therapy has been demonstrated to be superior to external beam radiation therapy and possibly surgery alone for the treatment of carcinoma of the esophagus. The combination of 5-fluorouracil (5-FU), cisplatin, and recombinant interferon α2a (IFN) has yielded 65% response rates in metastatic and regionally advanced carcinoma of the esophagus. A phase I-II study was performed to assess the feasibility of combining 5-FU, IFN, and cisplatin with external beam radiation therapy followed by surgery in potentially resectable patients. Eligibility included biopsy-proven stage II-III squamous cell or adenocarcinoma of the esophagus with no prior therapy. External beam radiation therapy was administered concurrently with chemotherapy beginning on day 1, 5 days per week, twice a day with 1.5 Gy/fraction to a total dose of 45 Gy. 5-FU was administered at 750 mg/m2 on days 1, 8, 15, 22, and 29 after the administration of IFN and cisplatin. IFN was given at a dose of 6 million units subcutaneously three times per week beginning on day 1. Dose levels I, II, and III of cisplatin were 25, 30, and 35 mg/m2 administered on days 1, 8, 15, 22, and 29. The sequence of administration was IFN followed by cisplatin followed immediately by 5-FU. Dose escalation between patient cohorts occurred if 0/3 or ≤ 1/6 patients had dose-limiting toxicity, i.e., grade II-III toxicity attributable to cisplatin. A phase II trial was planned using the maximum tolerated dose of cisplatin determined from the phase I trial. Patients who successfully completed therapy underwent thoracic exploration to resect residual disease. Twelve patients were enrolled; all were eligible. The demographics of the population were median age, 60 years (range, 44-77); nine male and three female patients; nine squamous cell carcinoma, one adenocarcinoma, and two adenosquamous histology; stage II:III, 2:10. Grade 3-4 toxicities included granulocytopenia (12 patients), thrombocytopenia (six), anemia (three), infection (six), diarrhea (two), mucositis (two), and renal and hepatic toxicities (one). Five patients had a clinical complete response, among whom four underwent surgery. At surgery, one patient had no evidence of residual disease and three patients had microscopic disease only. Two patients had progressive disease and five could not complete the therapy because of toxicities. Two patients are alive and disease free at 25 and 23 months, respectively. This regimen, though active, demonstrated an unfavorable toxicity profile and cannot be recommended for further study.

KW - Esophageal carcinoma

KW - Interferon α2a

KW - Multimodality therapy

UR - http://www.scopus.com/inward/record.url?scp=0033495761&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033495761&partnerID=8YFLogxK

U2 - 10.1097/00000421-199908000-00014

DO - 10.1097/00000421-199908000-00014

M3 - Article

VL - 22

SP - 391

EP - 395

JO - American Journal of Clinical Oncology

JF - American Journal of Clinical Oncology

SN - 0277-3732

IS - 4

ER -