Oxaliplatin and Fluorouracil Plus Radiation Therapy in Treating Patients With Primary Esophageal or Stomach Cancer

Albany Medical College

Status and phase: Completed; Phase 1

Conditions: Esophageal Cancer

Treatments: Procedure: conventional surgery; Drug: fluorouracil; Drug: oxaliplatin; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00004257

NCI-T99-0061

RPCI-DS-99-08

CDR0000067504

ALB-RPCI-DS-99-08

Details and patient eligibility

About

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 drug and combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining oxaliplatin and fluorouracil plus radiation therapy in treating patients who have primary esophageal or stomach cancer.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose and dose-limiting toxicity of oxaliplatin when given in combination with continuous-infusion fluorouracil and radiotherapy in patients with primary cancer of the thoracic esophagus or gastroesophageal junction.
• Determine the pharmacokinetics of this regimen in this patient population.
• Assess somatic p53 mutations in cancer of the esophagus and determine their relation to therapeutic response induced by this regimen.
• Assess, in a preliminary manner, the efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study of oxaliplatin and fluorouracil.

Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and fluorouracil IV continuously on days 8-42. Patients also undergo radiotherapy once daily, 5 days a week, for 6 weeks beginning on day 8.

Patients without evidence of distant disease or unresectable local regional invasion undergo esophageal resection between days 63-70 (within 3-4 weeks after completion of chemoradiotherapy). Patients then receive oxaliplatin as above on days 105, 119, and 133 and fluorouracil as above on days 105-147.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin and fluorouracil until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 4 weeks.

PROJECTED ACCRUAL: A total of 56 patients will be accrued for this study within approximately 3 years.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed primary squamous cell carcinoma or adenocarcinoma of the thoracic esophagus (below 20 cm from incisors) or gastroesophageal (GE) junction

  • Stage I-III
  • Bronchoscopy with biopsy and cytology required if primary esophageal cancer is less than 26 cm from incisors

• No disease outside esophagus and peri-esophageal soft tissue

• GE junction tumors must be confined to no greater than 2 cm into the gastric cardia

• Supraclavicular lymph nodes at station 1 must be less than 1.5 cm or nonpalpable by physical examination

  • Nodes 1.5 cm or greater or palpable by physical examination must be confirmed to be nonmalignant by biopsy

• Subdiaphragmatic lymph nodes at stations 15-20 must be no greater than 1.5 cm

• No recurrent disease

• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm3
• Granulocyte count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin normal
• AST/ALT no greater than 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN

Renal:

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No grade 2 peripheral neuropathy
• No history of allergy to platinum compounds
• No history of allergy to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
• No other concurrent uncontrolled illness
• No ongoing or active infection
• No other malignancy within the past 5 years

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No colony-stimulating factor therapy during first study course

Chemotherapy:

• No prior chemotherapy for esophageal cancer
• At least 4 weeks since other prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy for esophageal cancer
• At least 4 weeks since other prior radiotherapy

Surgery:

• No prior resection or attempted resection of esophageal cancer

Other:

• No other concurrent investigational drugs
• No other concurrent commercial agents or therapies for esophageal cancer
• No concurrent highly active antiretroviral agents (HAART) for HIV-positive patients