Preoperative chemotherapy in locally advanced and nonresectable gastric cancer: a phase II study with etoposide, doxorubicin, and cisplatin.
Thirty-four patients with locally advanced, nonresectable gastric cancer (staged by laparotomy) received etoposide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (EAP). Thirty-three patients were evaluable for response and toxicity. Second-look surgery with removal of residual tumor by gastrectomy and lymphadenectomy was performed in case of complete/partial remission (CR/PR) after EAP. After successful resection (R0- and R1-resection), two cycles of EAP were administered for consolidation therapy. Patients refusing reoperation received up to six cycles of EAP. The response rate (CR/PR) after EAP was 70% (23/33), including a 21% (7/33) rate of clinical CRs (CCRs). Two patients had minor remission (MR)/no change and seven had progressive disease. There was one early death. Nineteen of 23 responders (5 CCRs, 14 clinical PRs [CPRs]) and one patient with MR underwent second-look surgery. Five CCRs were pathologically confirmed; 10 patients with CPR were without evidence of disease (NED) after resection. In three patients (CPR), R1-resections (microscopically tumor-cell positive proximal margin) were performed; two patients are disease-free, 22+ and 33+ months after consolidation chemotherapy. In two patients, the tumor was again considered nonresectable. Twenty patients were disease-free after EAP +/- surgery +/- consolidation chemotherapy. Toxicity was primarily hematologic. Leukopenia and thrombocytopenia of World Health Organization (WHO) grade 3 occurred in 30% and 9%, respectively and grade 4 in 18% and 9% of the patients, respectively. There was no increased peri- or postoperative morbidity. After a median follow-up of 20 months for disease-free patients, the relapse rate is 60% (12/20). The median survival time for all patients is 18 months and for disease-free patients 24 months. EAP is highly effective in locally advanced gastric cancer, and offers a chance for surgery with curative intention in patients with an otherwise fatal prognosis.
Department of Hematology/Oncology, Hannover University, Medical School, West Germany.
H
H
Wilke
P
P
Preusser
U
U
Fink
U
U
Gunzer
H J
HJ
Meyer
J
J
Meyer
J R
JR
Siewert
W
W
Achterrath
L
L
Lenaz
H
H
Knipp
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007813:Laparotomy; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012074:Remission Induction; D012086:Reoperation; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery
D005047:Etoposide; D004317:Doxorubicin; D002945:Cisplatin