Oxaliplatin and Fluorouracil Plus Radiation Therapy in Treating Patients With Primary Esophageal or Stomach Cancer
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed 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.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263-0001 |
Sponsors and Collaborators
- Albany Medical College
- National Cancer Institute (NCI)
Investigators
- Study Chair: Lawrence P. Leichman, MD, Albany Medical College
Study Documents (Full-Text)
None provided.More Information
Publications
- CDR0000067504
- ALB-RPCI-DS-99-08
- RPCI-DS-99-08
- NCI-T99-0061