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

Albany Medical College

Overview

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.

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.

Study Type

INTERVENTIONAL

Purpose

TREATMENT

Conditions

Esophageal Cancer

Interventions

fluorouracilDRUG

oxaliplatinDRUG

conventional surgeryPROCEDURE

radiation therapyRADIATION

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (1)

Roswell Park Cancer Institute

Buffalo, New York, United States

Data from ClinicalTrials.gov

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