Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study.

BACKGROUND: Patients with locally advanced gastric cancer (cT3, cT4, N+, M0) have a dismal prognosis, despite complete resection. The objective of this study was to evaluate the toxicity and efficacy of neoadjuvant chemotherapy using the PLF (cisplatin/leucovorin [folinic acid]/5-fluorouracil [FU]) regimen in these patients. Primary endpoints of the study were the toxicity and the response to chemotherapy. Secondary endpoints were the rate of complete resection, survival, and first site of failure.
METHODS: Forty-nine patients with adenocarcinoma of the stomach were enrolled. Staging was based on abdominal computed tomography (CT) scans, endosonography, and laparoscopy. The intention was to administer two cycles (each containing six courses) of preoperative chemotherapy, consisting of cisplatin 50 mg/m(2), high-dose folinic acid (HD-FA) 500 mg/m(2), and HD 5-FU (HD-5-FU) 2000 mg/m(2) (PLF). Following chemotherapy all patients were referred to surgery. To be evaluable for response, survival, and first site of failure, the patient had to receive at least one cycle of chemotherapy.
RESULTS: Toxicity observed was low, with grade 3 toxicity in fewer than 5% of the patients and two events of grade 4 toxicity (diarrhea and pulmonary embolism). Forty-two of the patients (86%) received at least one cycle of chemotherapy. The clinical response rate in these patients was 26% (11/42 patients). In 76% of the patients (32/42), a complete resection was possible. The median duration of follow-up for the surviving patients was 58 months (range, 38 to 80+ months). The median survival time for the 42 patients assessable for response was 25.4 months (range, 6 to 80+ months). After complete resection, median survival time was 32 months (range, 7.6 to 80+ months). The median survival time for clinically responding patients has not yet been determined, but 5-year survival is 90%. Twenty of the 32 completely resected patients (62.5%) had recurrences. First site of failure was peritoneal dissemination in 10 patients; locoregional and distant recurrences were rare.
CONCLUSION: Neoadjuvant chemotherapy with PLF in patients with locally advanced gastric cancer has low toxicity and reasonable efficacy, allowing administration on an outpatient basis. Clinically responding patients have an excellent outcome after complete resection. The development of peritoneal dissemination even after neoadjuvant chemotherapy and complete resection remains an unsolved problem in patients with nonintestinal type tumors.