title: Neoadjuvant chemotherapy followed by salvage surgery: effect on survival of patients with primary noncurative gastric cancer.
abstract: The prognosis for gastric cancer patients who undergo noncurative resection is extremely poor. This study evaluated the effects of neoadjuvant chemotherapy for primary noncurative gastric cancer. Thirty-four patients with biopsy-proven noncurative gastric cancer were treated with either of two neoadjuvant chemotherapies: FEMTXP (5-fluorouracil, epirubicin, methotrexate, cisplatin) or THP-FLPM (pirarubicin, 5-fluorouracil, leucovorin, cisplatin, mitomycin C). Noncurability was determined by conventional staging procedures, staging laparoscopy, and exploratory laparotomy. After chemotherapy the resectability of the tumors was reassessed. Patients who were judged to be candidates for curative resection underwent salvage surgery. Of the final 33 patients, 8 (24.2%) showed a major response [0 complete response (CR), 8 partial response (PR)]. In three patients the second laparoscopy revealed disappearance of the peritoneal metastasis. Of the 33 patients, 14 (42.4%) underwent salvage surgery, including 8 curative resections (2 curability A, 6 curability B). Pathologic examinations revealed a grade 2 response in eight patients but no grade 3 response. Univariate analysis showed the following to be significant prognostic factors: histology type (differentiated type vs. undifferentiated type; p = 0.035), T4 as a noncurative factor (T4 vs. T3 or less; p = 0.025), clinical response (PR + no change vs. progressive disease; p = 0.002), and salvage surgery (resected vs. unresected; p = 0.001). Among these factors, salvage surgery was found to be the only independent prognostic factor by multivariate analysis, with a relative risk of 0.253 and a 95% confidence interval of 0.066 to 0.974. The treatment was well tolerated. Major toxicities of WHO grade 3 or more were leukopenia in 20 (60.6%), gastrointestinal toxicities in 5 (15.2%), renal toxicities in 2 (6.1%), and alopecia in 1 (3.0%). In conclusion, neoadjuvant chemotherapy is effective for primary noncurative gastric cancer when salvage surgery can be performed. A chemotherapy regimen with a higher complete response rate would improve the prognosis of this dismal disease even more.
authors.affiliation: Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. myano@surg2.med.osaka-u.ac.jp
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shiozaki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inoue
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Tamura
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
authors.forename: Takushi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Tsujinaka
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D011300:Preoperative Care; D011379:Prognosis; D016879:Salvage Therapy; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016019:Survival Analysis
chemical_list: D015251:Epirubicin; D016685:Mitomycin; D004317:Doxorubicin; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate