A phase II trial of neoadjuvant cisplatin-fluorouracil followed by postoperative intraperitoneal floxuridine-leucovorin in patients with locally advanced gastric cancer.
BACKGROUND
The aim of the study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy with intravenous (i.v.) cisplatin and fluorouracil (5-FU), surgery and postoperative intraperitoneal (i.p.) floxuridine (FUdR) and leucovorin (LV) in patients with locally advanced gastric cancer.


METHODS
Preoperative staging was confirmed by laparoscopy (LAP). Two cycles of i.v. cisplatin (20 mg/m(2)/day, rapid infusion) and 5-FU (1000 mg/m(2), continuous 24-h infusion), given on days 1-5 and 29-34, were followed by a radical gastrectomy and a D2 lymphadenectomy. Patients having R0 resections were to receive three cycles of i.p. FUdR (1000 mg/m(2)) and LV (240 mg/m(2)), given on days 1-3, 15-17 and 29-31. Intraperitoneal chemotherapy was begun 5-10 days from surgery.


RESULTS
Thirty-eight patients were treated. Both preoperative and postoperative chemotherapy were well tolerated. T stage downstaging (pretreatment LAP versus surgical pathological stage) was seen in 23% of patients. The R0 resection rate was 84%. Neither an increase in postoperative morbidity nor operative mortality was noted. With a median follow-up of 43.0 months, 15 patients (39.5%) are still alive (median survival 30.3 months). Good pathologic response, seen in five patients (15%), was associated with better survival (P = 0.053). Peritoneal and hepatic failures were found in 22% and 9% of patients, respectively. Quality of life seemed to be preserved.


CONCLUSIONS
Neoadjuvant cisplatin/5-FU followed by postoperative i.p. FUdR/LV can be safely delivered to patients undergoing radical gastrectomy and D2 lymphadenectomy. The R0 resection and the survival rates are encouraging. An association between pathologic response and patient outcome was suggested.
Brenner
B
B
Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University of New York, New York 10021, USA.
Shah
M A
MA
Karpeh
M S
MS
Gonen
M
M
Brennan
M F
MF
Coit
D G
DG
Klimstra
D S
DS
Tang
L H
LH
Kelsen
D P
DP
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D016145:Endoscopy, Digestive System / Q000009:adverse effects; D005240:Feasibility Studies; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage* / Q000009:adverse effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007274:Injections, Intraperitoneal; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D009367:Neoplasm Staging; D011184:Postoperative Period; D011788:Quality of Life; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D016019:Survival Analysis; D017211:Treatment Failure
D005467:Floxuridine; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil