Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: report of a clinical trial for patients with esophageal cancer.
OBJECTIVE
To identify a dose and schedule of oxaliplatin (OXP) to be safely administered in combination with protracted-infusion (PI) fluorouracil (5-FU) and external-beam radiation therapy (XRT) for patients with primary esophageal carcinoma (EC).


METHODS
Eligibility included therapeutically naïve EC patients with clinical disease stages II, III, or IV. Initial doses and schedules for cycle 1 consisted of OXP 85 mg/m(2) on days 1, 15, and 29; PI 5-FU 180 mg/m(2) for 24 hours for 35 days; and XRT 1.8 Gy in 28 fractions starting on day 8. At completion of cycle 1, eligible patients could undergo an operation or begin cycle 2 without XRT. Postoperative patients were eligible for cycle 2. Stage IV patients were allowed three cycles in the absence of disease progression. OXP and 5-FU increases were based on dose-limiting toxicity (DLT) encountered in cohorts of three consecutive patients.


RESULTS
Thirty-eight eligible patients received therapy: 22 noninvasively staged as IV and 16 noninvasively staged as II and III. Thirty-six patients completed cycle 1, 29 patients started cycle 2, and 24 patients completed cycle 2. The combined-modality therapy was well tolerated, but DLT prevented OXP and 5-FU escalation. No grade 4 hematologic toxicity was noted. Eleven grade 3 and two grade 4 clinical toxicities were noted in eight patients. After cycle 1, 29 patients (81%) had no cancer in the esophageal mucosa. Thirteen patients underwent an operation with intent to resect the esophagus; five patients (38%) exhibited pathologic complete responses.


CONCLUSIONS
OXP 85 mg/m(2) on days 1, 15, and 29 administered with PI 5-FU and XRT is safe, tolerable, and seems effective against primary EC. The role of OXP in multimodality regimens against EC deserves further evaluation.
Khushalani
Nikhil I
NI
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
Leichman
Cynthia Gail
CG
Proulx
Gary
G
Nava
Hector
H
Bodnar
Lisa
L
Klippenstein
Donald
D
Litwin
Alan
A
Smith
Judy
J
Nava
Enriqueta
E
Pendyala
Lakshmi
L
Smith
Patrick
P
Greco
William
W
Berdzik
Joanne
J
Douglass
Harold
H
Leichman
Lawrence
L
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil