Preoperative chemotherapy in locally advanced and nonresectable gastric cancer: a phase II study with etoposide, doxorubicin, and cisplatin.

Abstract

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.

Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy

“…Preoperative chemotherapy consisted of 3 cycles of etoposide, doxorubicin, and cisplatin (EAP, range, 1-4 cycles). 18 Nine patients were not able to complete the entire regimen due to drug toxicity, deterioration of performance status, or tumor progression. After an average of 28 days after completion of the chemotherapy, 36 patients underwent a total or extended gastrectomy with a D2 lymphadenectomy i.e., Ͼ 25 lymph nodes were excised) with curative intent.…”

Epirubicin, cisplatin and continuous infusion 5-fluorouracil (ECF) as neoadjuvant chemotherapy in gastro-oesophageal cancer

“…Only one of our unresectable group achieved complete surgical clearance of their disease following chemotherapy, which is disappointing when compared with other series in which chemotherapy has more successfully rendered inoperable disease operable (Wilke et al, 1989;Hill et al, 1995). One reason for this may be that five of our unresectable group had been classified unresectable at laparotomy, which may represent a worse prognostic group than those classified unresectable by radiological means alone.…”

“…Evidence that chemotherapy may render inoperable disease operable and produce complete pathological responses provides further encouragement (Wilke et al, 1989).…”

“…A number of trials have tested neoadjuvant chemotherapy in both initially resectable and unresectable gastric cancer with response rates of between 50% and 80% reported (Findlay and Cunningham, 1993). In one series, 45% of patients with unresectable disease achieved a complete resection after chemotherapy, and of these one-third were found to have a pathological complete-response (Wilke et al, 1989).…”

A multimodal treatment approach including high-dose chemotherapy in very advanced gastric cancer: evidence for control of metastatic disease

“…[18][19][20][21] Therefore, retrospective studies are ongoing to define the potential chemosensitivity on a molecularpathologic basis from biopsies of the primary tumor site. From our results, patient selection for a multimodal treatment approach should be based on (1) favorable ECOG status and (2) non-extra-abdominal metastatic disease.…”