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 more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: Randomized phase I/II trial to study the effectiveness of combination chemotherapy with or without paclitaxel combined with radiation therapy in treating patients who have stage II or stage III cancer of the esophagus.

Condition	Treatment or Intervention	Phase
stage II esophageal cancer stage III esophageal cancer	Drug: fluorouracil  Drug: hydroxyurea  Drug: paclitaxel  Procedure: chemotherapy  Procedure: conventional surgery  Procedure: radiation therapy  Procedure: surgery	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Compare the efficacy of concurrent radiotherapy with fluorouracil and hydroxyurea with or without paclitaxel in terms of survival without dysphagia in patients with inoperable stage II or III epidermoid carcinoma of the esophagus.
• Compare the overall survival, response rate, toxicity, and quality of life in this patient population treated with these regimens.

OUTLINE: This is a randomized, open label, multicenter study. Patients are stratified according to weight loss (less than 10% vs at least 10%) and inoperability criteria (nonresectable vs due to anatomical terrain). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive fluorouracil IV continuously, oral hydroxyurea, and concurrent radiotherapy daily on days 1-5.
• Arm II: Patients receive fluorouracil, hydroxyurea and radiotherapy as in arm I. Patients also receive paclitaxel IV on day 1. Treatment continues every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients with possible resectable disease undergo surgical resection at 4-6 weeks following the last course of chemoradiotherapy. Patients with continued unresectable disease receive 2 additional courses of chemoradiotherapy as above within 8-17 days following the last course of chemoradiotherapy.

Quality of life is assessed at baseline, monthly during therapy, every 2 months for 6 months, every 4 months for 1 year, and then every 6 months thereafter.

Patients are followed every 2 months for 6 months, every 4 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A maximum of 90 patients will be accrued for this study.

Ages Eligible for Study:  18 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage II (T2 or T3, N0, M0) or III (T3, N1, M0) epidermoid carcinoma of the esophagus
• Inoperable due to initial extension or inoperable with no extension
• No visceral metastases
• No extension to the tracheo-bronchial pathway
• No tracheo-esophageal fistula
• No broncho-esophageal fistula
• No suspected respiratory mucosal involvement on bronchoscopy
• No carcinoma in situ

PATIENT CHARACTERISTICS: Age:

• 18 to 80

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count at least 120,000/mm^3
• Hemoglobin at least 10 g/dL
• Neutrophil count at least 1,500/mm^3
• Lymphocyte count at least 1,000/mm^3

Hepatic:

• SGOT and SGPT no greater than 2 times normal
• Albumin at least 3.0 g/dL

Renal:

• Creatinine no greater than 1.4 mg/dL
• Calcium less than 11.2 mg/dL

Pulmonary:

• See Disease Characteristics
• No severe respiratory illness (e.g., severe broncho-pathway obstruction or insufficient respiration)
• No uncontrolled broncho-pulmonary infection

Other:

• No other prior history of malignancy except curatively treated carcinoma in situ of the colon or skin cancer
• No contraindication to fluorouracil
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No psychiatric illness
• HIV negative
• Total protein at least 65% of normal

PRIOR CONCURRENT THERAPY: Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• No prior endocrine therapy

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No concurrent participation in other study

France
      C.H. Senlis, Senlis,  60309,  France
      Centre Jean Bernard, Le Mans,  72000,  France
      CHR de Grenoble - La Tronche, Grenoble,  F-38043,  France
      Clinique Fleming, Tours,  37000,  France
      Clinique Saint - Jean, Cagne-sur-Mer,  06800,  France
      Clinique Saint Vincent, Besancon,  25044,  France
      Clinique Ste - Marie, Pontoise,  95301,  France
      CMC Les Ormeaux, Le Havre,  76600,  France
      Hopital Andre Mignot, Le Chesnay,  78157,  France
      Hopital Laennec, Paris,  75007,  France
      Hopital Saint Antoine, Paris,  75571,  France
      Hopital Saint-Louis, Amiens,  80054 Cedex 1,  France
      Hopital Tenon, Paris,  75970,  France
      Polyclinique De Courlancy, Reims,  F-51100,  France

Study chairs or principal investigators

Gerard Ganem, MD,  Study Chair,  Centre Jean Bernard   

Study ID Numbers:  CDR0000068368; FRE-GERCOR-D99-1; EU-20021
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  January 6, 2001
ClinicalTrials.gov Identifier:  NCT00008047
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08