Phase II Study with Folinic Acid, Etoposide, 5-Fluorouracil and Cisplatin (FLEP) for Advanced Gastric Cancer

Abstract

Background: Cisplatin is an active drug in advanced gastric cancer and acts synergis-tically with etoposide and 5-fluorouracil (5-FU). These were the reasons for adding cisplatin (P) to the combination of folinic acid, etoposide, and 5-FU (ELF), which is one of the newer and active regimens for the treatment of advanced gastric cancer. Patients and Methods: 29 patients with advanced gastric cancer were treated with folinic acid (300 mg/m2), etoposide (100 mg/m2), 5-FU (500 mg/m2), and cisplatin (30 mg/m2) intravenously on days 1, 2, and 3. Cycles were repeated on days 22-28. Results: 2 (7%) complete and 9 (31%) partial remissions were achieved. The medium remission duration was 6 months and the median survival time was 7 months. The main toxicity of FLEP was severe myelosuppression of WHO grades 3 and 4 leucocytopenia in 38 and 21 % of the patients. Conclusions: FLEP is an active regimen for gastric cancer with respect to remission induction. However, because of the marked objective and subjective side effects, and a response rate which was not different from ELF alone, the further evaluation of this combination is not meaningful in this tumor.

Wilke H, et al.: Phase II study with folinic acid, etoposide, 5-fluorouracil and cisplatin (FLEP) for advanced gastric cancer. Onkologie 1994;17:154-157 (this issue)

“…Usually, oncologists feel compelled to treat patients suffering from chemosensitive cancer like gastric cancer with intensive chemotherapy based on mostly uncontrolled phase II studies promising to be more effective than so-called standard treat ments. However, considering the most important treatment goal in non-curable disease to provide the patient palliation and a higher quality of life, it must be recognized that intensi fied chemotherapies in gastric cancer, such as EAP [2,3] or, currently FLEP [4] have been dismal failures. Toxicity of those treatment protocols is unacceptably severe for patients with incurable disease, and remission rates as well as survival bene fit are not significantly superior to ELF [5], FAM or even 5-FU alone [6].…”

“…These results require further investi gations preferably by comparing FAMTX with well-tolerated ELF regimen. Once again, we have to face two facts: Firstly, intensified com bination chemotherapy based on a positive biochemical in vitro interaction of cytotoxic agents, like the proven synergism of cisplatin, 5-FU and folinic acid [8] as rationale for the FLEP regimen [4], is no guarantee for a better outcome of the cancer patient. Secondly, only controlled comparative clinical trials can tell what is best for the patient with advanced gastric cancer.…”