Phase I trial of oxaliplatin in combination with cisplatin, protacted-infusion fluorouracil, and radiotherapy in advanced esophageal and gastroesophageal carcinoma.
OBJECTIVE
To define the maximum-tolerated dose of oxaliplatin given with cisplatin, protacted 96-h infusion of fluorouracil, and radiotherapy for patients with advanced esophageal cancer.


METHODS
Seventeen patients with locally advanced esophageal cancer and 2 patients with local recurrence were treated. Escalating doses of oxaliplatin, cisplatin, and fluorouracil were administered on Days 1 and 29 of radiotherapy. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy. Dose-limiting toxicity was defined as a Grade 4 hematologic or Grade 3-4 nonhematologic toxicity.


RESULTS
Dose-limiting toxicity caused by diarrhea and asthenia was observed at the IV level. The recommended dose was 85 mg/m- oxaliplatin, 55 mg/m2 cisplatin, and 3000 mg/m2 96-h fluorouracil infusion. Two pathologic complete responses were observed in 12 patients selected for surgery (16%).


CONCLUSIONS
Oxaliplatin, cisplatin, fluouracil, and radiotherapy can be administered together with acceptable toxicity. A Phase II trial is ongoing with resectable esophageal and gastric carcinoma.
Maurel
Joan
J
Department of Medical Oncology, Hospital Clinic Barcelona, Institut D'Investigacìons Bìomèdìques August Pi i Sunyer, University of Barcelona, Barcelona, Spain. jmaurel@clinic.ub.es
Cervantes
Andrés
A
Conill
Carlos
C
Salazar
Ramón
R
Martin-Richard
Marta
M
Pera
Manuel
M
Manzano
Hermini
H
Chirivella
Isabel
I
Gallego
Rosa
R
Marfa
Xavier
X
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011879:Radiotherapy Dosage
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002945:Cisplatin; D005472:Fluorouracil