title: Neoadjuvant chemotherapy in locally advanced gastric carcinoma--a phase II trial with combined continuous intravenous 5-fluorouracil and bolus cisplatinum.
abstract: Locally advanced gastric adenocarcinomas (LAGC) have a poor prognosis, particularly when tumours are bulky, located in the cardia or in the event of locoregional lymph node involvement. Patients bearing these tumours were entered in a phase II trial of neoadjuvant chemotherapy, combining continuous intravenous 5-fluorouracil (5FU) (1000 mg/m2 for 5 days) and cisplatinum (CDDP) (100 mg/m2 on day 2) repeated every 4 weeks, for one to six cycles according to response and tolerance. 30 patients have been entered, 26 after clinical evaluation (CAT scan and upper gastrointestinal endoscopy) and 4 with unresectable tumours at prior laparotomy. Median age was 60 years, 15/30 patients had a tumour of the cardia, 15/30 had enlarged lymph nodes and 7/30 had linitis plastica (diffuse type). A mean number of three cycles was administered (range 1-6). 27 of the 30 patients were evaluable for response. One patient achieved a complete response (CR) and 14 a partial response (56%; 95% confidence interval 38-74%). No patient had tumour progression, and only 1/6 with linitis plastica responded. 28 patients underwent surgery, and 23 had a macroscopically complete resection (77% of the 30 entered patients); RO resections were performed in 60% of the cases, mainly after an objective response (13/15 versus 4/12 in nonresponders). No pathological CR were seen. Grade 4 neutropenia was observed in eight cycles (5 patients), with five septic complications and one death due to toxicity. Four postoperative complications were observed: 2 cases of severe pneumonia and 2 subphrenic abscesses. One postoperative death, due to intravascular disseminated coagulation, was observed at day 30. Median survival was 16 months and the 1-, 2- and 3-year survival was 67, 42 and 38%, respectively. Patients with linitis plastica had a significantly shorter survival (P < 0.002). We conclude that neodjuvant chemotherapy is feasible in LAGC, although randomised trials are warranted to demonstrate its efficacy on survival and resection rates.
authors.affiliation: Gastro-Intestinal Unit, Institut Gustave Roussy, Villejuif, France.
authors.forename: P
authors.initials: P
authors.lastname: Rougier
authors.forename: M
authors.initials: M
authors.lastname: Mahjoubi
authors.forename: P
authors.initials: P
authors.lastname: Lasser
authors.forename: M
authors.initials: M
authors.lastname: Ducreux
authors.forename: J
authors.initials: J
authors.lastname: Oliveira
authors.forename: M
authors.initials: M
authors.lastname: Ychou
authors.forename: J P
authors.initials: JP
authors.lastname: Pignon
authors.forename: D
authors.initials: D
authors.lastname: Elias
authors.forename: S
authors.initials: S
authors.lastname: Bellefqih
authors.forename: C
authors.initials: C
authors.lastname: Bognel
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D005472:Fluorouracil