Intensive weekly chemotherapy for locally advanced gastric cancer using 5-fluorouracil, cisplatin, epidoxorubicin, 6S-leucovorin, glutathione and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD)

Abstract

Summary Local extension prevents curative resection in more than two-thirds of gastric cancer patients. Unfortunately, resectability is one of the main prognostic factors in these patients, and survival is longer when tumours are completely removed. Preoperative chemotherapy is an attractive concept for obtaining curative resection. Thirty-two locally advanced unresectable gastric cancer patients were enrolled in five Italian Group for the Study of Digestive Tract Cancer (GISCAD) centres. For 16 patients, surgical unresectability was based on computerized tomography scan evaluation of tumour size (four patients) and invasion of adjacent structures (12 patients), whereas in another 16 patients locally advanced disease was confirmed by laparotomy. They received weekly administration of cisplatin 40 mg m-2. 5-fluorouracil 500 mg in-2, epidoxorbicin 35 mg m-2, 6S-stereoisomer of leucovorin 250 mg rT2 and glutathione 1.5 g m-2. From the day after to the day before each chemotherapy administration, filgrastim was administered by subcutaneous injection at a dose of 5 lig kg-'. One cycle of therapy consisted of eight weekty treatments. Fifteen of 32 patients (470o) responded to chemotherapy, whereas 13 (410%) had stable disease and four (12°h) progressed on therapy. Of the 15 responding patients, 13 were completely resected after chemotherapy and two of them had a complete pathological response. Two clinically responding patients were found unresectable at operation because of perntoneal seeding. At a median follow-up from the start of treatment of 24 months (range 11-39 months), 10 of 13 resected patients are alive and eight are relapse free. Three patients died after 11, 12. and 14 months respectively. Toxicity was acceptable: side-effects consisted mainly of grade 11 National Cancer Institute common toxicity criteria (NCICTC) leucopenia and thrombocytopenia in ten patients. Neither treatment-related death nor surgical complications in patients undergoing surgery were observed. This weekly intensive regimen enabled resection in half of previously inoperable tumours with a moderate toxicity. It can be offered to patients with locally advanced unresectable gastric cancer to obtain curative resection.

A phase II study of sequential chemotherapy with docetaxel after the weekly PELF regimen in advanced gastric cancer. A report from the Italian group for the study of digestive tract cancer

“…In advanced gastric cancer, we investigated safety and activity of sequential chemotherapy with docetaxel after the intensive weekly PELF regimen (Cascinu et al, 1997(Cascinu et al, , 1998.…”

Infusional 5-fluorouracil, cisplatin and mitomycin C in advanced gastric cancer: A low cost effective regimen

“…The choice of these drugs and schedule was made based on the following: 5-FU, epiADR and CDDP remain the most active single agents in gastric cancer (Schipper and Wagener, 1996); 5-FU and CDDP are potentially synergistic (Leichman and Berry, 1991); LV can enhance 5-FU activity (Arbuck et al, 1987); weekly administration allows more drug to be administered per unit time, which minimizes side effects (Young, 1990); filgrastim may contribute to perform weekly administrations of drugs reducing the incidence of neutropenia. This weekly intensive regimen confirmed its activity also in locally advanced gastric cancer enabling resection on half of previously inoperable tumour with a moderate toxicity (Cascinu et al, 1998), and now a randomized trial in the adjuvant setting is being carried out in Italy.…”

A phase II study of weekly cisplatin, 6S-stereoisomer leucovorin and fluorouracil as first-line chemotherapy for elderly patients with advanced gastric cancer

“…This demographic selection occurred in the populations of gastric cancer patients treated with intensive combination chemotherapy regimens like the ECF (Tebbutt et al, 2002) or the weekly PELF. The weekly PELF (cisplatin, fluorouracil, epi-doxorubicin, leucovorin) regimen plus filgrastim support yielded a 62% response rate and a median survival time of 11 months in a large phase II trial (Cascinu et al, 1997). This efficacy was confirmed in subsequent studies (Cascinu et al, 1998(Cascinu et al, , 2001), but demographic data suggest that only a minority of patients treated with the weekly PELF regimen were older than 65 years.…”

“…The weekly PELF (cisplatin, fluorouracil, epi-doxorubicin, leucovorin) regimen plus filgrastim support yielded a 62% response rate and a median survival time of 11 months in a large phase II trial (Cascinu et al, 1997). This efficacy was confirmed in subsequent studies (Cascinu et al, 1998(Cascinu et al, , 2001), but demographic data suggest that only a minority of patients treated with the weekly PELF regimen were older than 65 years. In the PELF trials, severe haematology and nonhaematologic toxicities were uncommon, but more than half of the patients had mild-to-moderate side effects and even using routine filgrastim support, up to one-third of patients showed grade II or III neutropenia (Cascinu et al, 1997(Cascinu et al, , 1998(Cascinu et al, , 2001.…”

“…In recent years, secondgeneration combination chemotherapy regimens have produced high response rates and impressive survival times (Cascinu et al, 1997;Webb et al, 1997;Hill and Cunningham, 1998). However, the activity of these treatments has been demonstrated in patients with good performance status and young age and, therefore, they do not reflect the characteristics of patients in the community with advanced gastric cancer (Tebbutt et al, 2002).…”