A Phase I Study of Oxaliplatin in Combination With Continuous Infusion 5-Fluorouracil and Radiation in Esophageal Cancer
fluorouracil
+ oxaliplatin
+ conventional surgery
Carcinome+12
+ Carcinome à cellules squameuses
+ Maladies du système digestif
Étude thérapeutique
Résumé
Date de début de l'étude : 1 janvier 2000
Date à laquelle le premier participant a commencé l'étude.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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.À partir de 18 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
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
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 1 site
Roswell Park Cancer Institute
Buffalo, United StatesOuvrir Roswell Park Cancer Institute dans Google Maps