High curative resection rate with weekly cisplatin, 5-fluorouracil, epidoxorubicin, 6S-leucovorin, glutathione, and filgastrim in patients with locally advanced, unresectable gastric cancer: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)

Abstract

The aim of the present study was to evaluate the role of a weekly preoperative chemotherapy in locally advanced, unresectable gastric cancer. In all, 82 patients with an Eastern Oncology Cooperative Group PS p2 and normal cardiac function were enrolled onto the study. Surgical unresectability was confirmed in 52 patients (63%) at laparotomy, and in 30 (27%) cases by CT scan of the abdomen and endoscopic ultrasonography. Chemotherapy treatment was: cisplatin 40 mg m À2 ; 5-fluorouracil 500 mg m À2 ; epidoxorubicin 35 mg m À2 ; 6S-leucovorin 250 mg m À2 and glutathione 1.5 g m À2 (PELF). One cycle consisted of 8 weekly treatments. Response to chemotherapy was observed in 40 of 82 patients (49%): six (7%) complete and 34 (41%) partial responses, and in four (5%) cases a complete pathological response was confirmed. Of the 40 responding patients, 37 (45%) had potentially curative surgery. Grade 3/4 leucopenia and thrombocytopenia occurred in three and two patients. At a median follow-up of 48 months, 25 of the 37 resected patients (68%) were alive and 24 (65%) were disease free. The median and 4-year survival for the whole group was 17 months and 31%, respectively. The median survival was 12 months for inoperable patients and it was not reached in resected patients.

Neoadjuvant Radiochemotherapy in Locally Advanced Gastric Carcinoma

“…Besides RCT, neoadjuvant chemotherapy alone is often practiced, even though larger studies on this topic are missing. More recent studies show response rates of 25-50% [3,25,37]; the response rates are likely to be better with the use of more modern chemotherapy agents such as taxanes or irinotecan. Here, response rates of up to 58% can be achieved, although shown only in small phase I/II studies [15]; nevertheless, these rates are still below those observed after RCT.…”

“…Looking at the CR rates achievable by neoadjuvant chemotherapy, these are still clearly lower than the CR rates which can be achieved using neoadjuvant RCT. By comparison, the CR rates after chemotherapy are between 0% and a maximum of 7% [3,16,25]; our patients achieved a rate of 14% after neoadjuvant RCT. The prognostic importance of CR in gastric carcinoma is unclear; in carcinoma of the esophagus, however, patients with CR after neoadjuvant RCT have a higher median survival [4,6,35].…”

Current strategies in systemic treatment of gastric cancer and cancer of the gastroesophageal junction

“…In 6 studies including a total of 264 deWnitely irresectable patients, most of them deWned by laparotomy, R-0-resections were achieved in 14-45% (Wilke et al 1989;Plukker et al 1991;Lerner et al 1992;Cascinu et al 1998;Gallardo-Rincon et al 2000;Cascinu et al 2004). In a study of our group on patients staged either by laparotomy or by endoscopic ultrasound, computed tomography and, in case of conXicting results, surgical laparoscopy, we achieved a 52% R-0-resection rate among 25 patients of stage IIIB and IV M0 (Menges et al 2003) (Table 1).…”

Negative Predictive Value of Preoperative Computed Tomography in Determining Pathologic Local Invasion, Nodal Disease, and Abdominal Metastases in Gastric Cancer

“…Because local invasion of adjacent structures constitutes an indication for multivisceral resection (likely with neoadjuvant therapy) or nonoperative management 10 , and because the present analysis excluded patients receiving neoadjuvant therapy or nonoperative management, it is appropriate that only a small proportion of patients had locally invasive disease. Because npv depends on the prevalence of a given finding within the population under investigation, the North American cohort analyzed, which typically presents with a higher incidence of local invasion, nodal metastasis, and distant metastases than is found in cohorts from Eastern countries 9 , will demonstrate a correspondingly different npv.…”