oxaliplatin and fluorouracil plus radiation therapy in treating patients with primary esophageal or stomach cancer

Conditions: Esophageal Cancer

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.

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.

Eligibility 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

Keywords: stage i esophageal cancer stage ii esophageal cancer stage iii esophageal cancer squamous cell carcinoma of the esophagus adenocarcinoma of the esophagus