Combination Chemotherapy Plus Radiation Therapy With or Without Fluorouracil in Treating Patients With Cancer of the Esophagus or Stomach

Non-Operative Therapy Of Local-Regional Carcinoma Of The Esophagus: A Randomizd Phase II Study Of Two Paclitaxel-Based Chemoradiotherapy Regimens

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: Randomized phase II trial to compare the effectiveness of combination chemotherapy plus radiation therapy with and without fluorouracil in treating patients who have cancer of the esophagus or stomach.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Esophageal Cancer
• Intervention / Treatment: Drug: fluorouracil; Radiation: radiation therapy; Drug: cisplatin; Drug: paclitaxel; Biological: filgrastim

Detailed Description

OBJECTIVES:

• Compare the survival and failure patterns in patients with previously untreated carcinoma of the esophagus or gastroesophageal junction treated with cisplatin, paclitaxel, and concurrent radiotherapy with or without fluorouracil.
• Compare the tolerance of these regimens by these patients.
• Compare the overall quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to percentage of weight loss (less than 10% vs 10% or more), disease histology (adenocarcinoma vs squamous cell carcinoma), and lesion size (no more than 5 cm vs more than 5 cm). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive induction chemotherapy comprising fluorouracil IV continuously over 24 hours and cisplatin IV over 1 hour on days 1-5, paclitaxel IV continuously over 24 hours on day 1, and filgrastim (G-CSF) subcutaneously daily on days 6-15. Treatment repeats every 4 weeks for up to 2 courses. Patients with stable or responsive disease after the first course of induction therapy receive a second course of therapy. Patients with local disease progression after the first course proceed to chemoradiotherapy.

Beginning on day 29 of the last course of induction chemotherapy, patients undergo radiotherapy 5 days a week for 5.5 weeks. Patients also receive fluorouracil IV continuously over 24 hours on days 1-5, 8-12, 15-19, 22-26, and 29-33, and paclitaxel IV over 3 hours on days 1, 8, 15, 22, and 29.

• Arm II: Patients receive induction chemotherapy comprising cisplatin IV and paclitaxel IV over 3 hours on day 1. Treatment continues every 3 weeks for 2 courses as in arm I.

Beginning on day 29 of the last course of induction chemotherapy, patients undergo radiotherapy as in arm I. Patients also receive cisplatin IV on days 1, 8, 15, 22, 29, and 36, and paclitaxel IV continuously over 96 hours on days 1-4, 8-11, 15-18, 22-25, 29-32, and 36-39.

Quality of life is assessed at baseline, within 1 week after radiotherapy, at 6 weeks after study completion, every 4 months for 1 year, every 6 months for 2 years, and then annually for 5 years.

Patients are followed within 8 weeks, every 4 months for 1 year, every 6 months for two years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 84 patients (42 per treatment arm) will be accrued for this study within 21 months.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Foundation for Cancer Research and Education
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Northridge, California, United States, 91328
      • Leavey Cancer Center at Northridge Hospital Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610-0385
      • University of Florida Shands Cancer Center
    • Miami, Florida, United States, 33176-2197
      • Baptist-South Miami Regional Cancer Program
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Illinois
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Veterans Affairs Medical Center - Indianapolis (Roudebush)
    • Muncie, Indiana, United States, 47303-3499
      • Cancer Center at Ball Memorial Hospital
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • Terre Haute, Indiana, United States, 47804
      • Union Hospital
  • Iowa
    • Dubuque, Iowa, United States, 52001
      • Wendt Regional Cancer Center at Finley Hospital
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Esther Marie Hatton Cancer Care Center at St. Elizabeth Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112-2699
      • Tulane Cancer Center at Tulane University Hospital and Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Greenebaum Cancer Center at University of Maryland Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
  • Minnesota
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • CCOP - Kansas City
  • Nebraska
    • Omaha, Nebraska, United States, 68114-4199
      • Methodist Hospital Cancer Center at Nebraska Methodist Hospital - Omaha
  • New Jersey
    • Long Branch, New Jersey, United States, 07740-6395
      • Monmouth Medical Center
    • Pomona, New Jersey, United States, 08240
      • Atlantic City Medical Center - Mainland Division
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate Medical Center
    • East Syracuse, New York, United States, 13057
      • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
  • North Carolina
    • Goldsboro, North Carolina, United States, 27533
      • Wayne Memorial Hospital, Incorporated
  • Ohio
    • Akron, Ohio, United States, 44304
      • Akron City Hospital at Summa Health System
    • Akron, Ohio, United States, 44302
      • Akron General's McDowell Cancer Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University
    • Columbus, Ohio, United States, 43206
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43222
      • Mount Carmel West Hospital
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Marietta, Ohio, United States, 45750-1635
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Newark, Ohio, United States, 43055-2899
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • Toledo, Ohio, United States, 43623-3456
      • CCOP - Toledo Community Hospital
  • Oregon
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Hospital Cancer Center
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Regional Cancer Center at Delaware County Memorial Hospital
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Dale and Frances Hughes Cancer Center at Pocono Medical Center
    • Paoli, Pennsylvania, United States, 19301-1792
      • Cancer Center at Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15219
      • Mercy Hospital of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15212-4772
      • Allegheny General Hospital
    • Reading, Pennsylvania, United States, 19612-6052
      • Reading Hospital and Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
  • Utah
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Sciences Center
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • CCOP - Marshfield Clinic Research Foundation
    • Menomonee Falls, Wisconsin, United States, 53051
      • Community Memorial Hospital
    • Milwaukee, Wisconsin, United States, 53295
      • Veterans Affairs Medical Center - Milwaukee (Zablocki)
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Racine, Wisconsin, United States, 53405
      • All Saints Cancer Center at All Saints Healthcare
    • Waukesha, Wisconsin, United States, 53188
      • Waukesha Memorial Hospital Regional Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed primary squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction

  • Stage I-III (T1, N1, M0; T2-4, N any, M0)

    • Supraclavicular or celiac lymph node involvement allowed
• Disease entirely confined to the esophagus or gastroesophageal junction and peri-esophageal soft tissue
• Cervical esophageal carcinoma allowed
• No tumor extension beyond 2 cm into stomach
• No multiple primary carcinomas of the esophagus
• No evidence of disseminated cancer

• No tracheoesophageal fistula or direct invasion into the mucosa of the trachea or major bronchi

  • Bronchoscopy with biopsy and cytology required if the primary carcinoma is less than 26 cm from the incisors or is at or above the carina by imaging study

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 150,000/mm^3
• Hemoglobin at least 10 g/dL

Hepatic:

• Not specified

Renal:

• Creatinine no greater than 1.5 mg/dL
• Creatinine clearance at least 65 mL/min

Cardiovascular:

• No uncontrolled heart disease
• No uncontrolled hypertension

Other:

• Total oral/enteral intake must be at least 1,700 kCal/day
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No uncontrolled diabetes
• No other malignancy within the past 5 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy
• No other concurrent chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior chest radiotherapy

Surgery:

• No prior major esophageal surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Ajani JA, Winter K, Komaki R, Kelsen DP, Minsky BD, Liao Z, Bradley J, Fromm M, Hornback D, Willett CG. Phase II randomized trial of two nonoperative regimens of induction chemotherapy followed by chemoradiation in patients with localized carcinoma of the esophagus: RTOG 0113. J Clin Oncol. 2008 Oct 1;26(28):4551-6. doi: 10.1200/JCO.2008.16.6918. Epub 2008 Jun 23.
• Komaki R, Winter K, Ajani J: Non-operative therapy of local-regional carcinoma of the esophagus: a randomized phase II study of two paclitaxel-based chemoradiotherapy regimens (RTOG 0113). [Abstract] The American Radium Society 89th Annual Meeting, May 5-29, 2007, Amsterdam, Netherlands. A-SS-2, 1, 2007.
• Komaki R, Winter K, Ajani A, et al.: A randomized phase II study of two paclitaxel-based chemoradiotherapy regimens for patients with the non-operative esophageal carcinoma (RTOG 0113). [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-142, S79-80, 2006.

Study record dates

Study Major Dates

• Study Start: April 1, 2001
• Primary Completion (Actual): July 1, 2006

Study Registration Dates

• First Submitted: February 2, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 19, 2013
• Last Update Submitted That Met QC Criteria: July 17, 2013
• Last Verified: July 1, 2004

More Information

Terms related to this study

• Keywords: stage III gastric cancer; stage II esophageal cancer; stage III esophageal cancer; adenocarcinoma of the stomach; squamous cell carcinoma of the esophagus; adenocarcinoma of the esophagus; stage I gastric cancer; stage II gastric cancer; stage I esophageal cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Stomach Neoplasms; Esophageal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Fluorouracil
• Other Study ID Numbers: RTOG-0113; CDR0000068420