Combination of Bolus 5-Fluorouracil, Folinic Acid and Mitomycin C in Advanced Gastric Cancer: Results of a Phase II Trial

Abstract

Background: Gastric carcinoma still is a worldwide major cause of cancer death. Although various chemotherapy schedules yielded high response rates, median survival rarely exceeds 8–10 months. Many regimens are inevitably associated with significant toxicity which jeopardizes their value as palliative treatment, especially in patients with reduced performances status. Therefore, we initiated a phase II study for the treatment of advanced gastric carcinoma using a bolus regimen with mitomycin C (MMC), 5-fluorouracil (5-FU) and folinic acid (FA), allowing the enrollment of elderly patients or those with reduced performance status (WHO grade 2). Patients and Methods: Between 1996 and 1998 we recruited a total of 58 patients with advanced gastric cancer to receive bolus MMC 3 mg/m², 5-FU 450 mg/m², and FA 100 mg/m² on days 1–3. Treatment was repeated on day 22. 53 patients met the inclusion criteria: male n = 36, female n =17; median age 65 (range 26–81); mean WHO status 1 (range 0–2). Results: Out of 53 patients 50 were evaluable for response, all 58 patients who received therapy were evaluable for toxicity. Eleven patients (22%) achieved partial remission (95% CI: 11.5 –36.0%), 24 (48%) no change and 15 (30%) were progressive. Median overall survival was 11.5 months, the median time to progression 6.0 months. Out of 290 treatment cycles the worst toxicities observed (WHO 2/3/4) were as follows: anemia 13/3/1, leukopenia 19/1/1, thrombopenia 11/3/0, nausea/emesis 11/2/0, infections 2/1/0, diarrhea 14/2/0, and stomatitis 6/1/1. One patient developed hemolytic-uremic syndrome. Conclusions: The tumor control rate (PR + NC) of 70% was comparable to established chemotherapy regimens, while median overall survival was promising. Toxicity was mild, allowing the treatment especially for elderly patients and on outpatient basis.