A phase II study of sequential neoadjuvant gemcitabine and paclitaxel, radiation therapy with cisplatin and 5-fluorouracil and surgery in locally advanced esophageal carcinoma.
OBJECTIVE
To evaluate the feasibility and efficacy of sequential neoadjuvant chemotherapy, chemoradiation, and surgery in patients with locally advanced esophageal cancer.


METHODS
There were 29 patients who received paclitaxel 150 mg/m2 and gemcitabine 3000 mg/m2 2 weeks apart. Two weeks later, patients received cisplatin 75 mg/m2 and 5-fluorouracil (5-FU) 1000 mg/m2/d continuous infusion for 4 days with concurrent radiotherapy in 15 fractions to a total dose of 4000 cGy. After 6 weeks, cisplatin and 5-FU were repeated at the above doses. After 4 to 6 weeks, patients were restaged and underwent surgical resection.


RESULTS
All 29 patients completed the prescribed gemcitabine, paclitaxel, and radiation therapy. Febrile neutropenia occurred in 1 patient and 4 patients received growth factor support. After neoadjuvant treatment, 1 patient refused surgery, 23 underwent R0 resection (82%), while 5 developed progressive disease. Four patients developed anastomotic leaks (17%). Four patients had complete pathologic responses (14%) and 4 (14%) had only residual microscopic disease. Nine patients remain alive at a median follow-up of 48 months. Three-year survival for the entire cohort was 36%.


CONCLUSIONS
This regimen was associated with a high rate of compliance and induction therapy had an acceptable toxicity profile. The R0 resection rate and 3-year survival data are similar to recently reported studies. While active, gemcitabine and paclitaxel induction therapy was associated with an increased rate of postoperative complications, but no increase in survival. Patterns of failure continue to demonstrate the need for regimens incorporating greater emphasis on systemic therapy for locally advanced esophageal cancer.
Lowy
Andrew M
AM
Department of Surgery, Division of Surgical Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA. andrew.lowy@uc.edu
Firdaus
Irfan
I
Roychowdhury
Debasish
D
Redmond
Kevin
K
Howington
John A
JA
Sussman
Jeffrey J
JJ
Safa
Malek
M
Ahmad
Syed A
SA
Reed
Michael F
MF
Rose
Patricia
P
James
Laura
L
Jazieh
Abdul Rahman
AR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine