Adjuvant chemoradiation using 5-fluorouracil/folinic acid/cisplatin with or without paclitaxel and radiation in patients with completely resected high-risk gastric cancer: two cooperative phase II studies of the AIO/ARO/ACO

Background: The current two studies evaluate the feasibility, toxicity and efficacy of an adjuvant combined modality treatment strategy containing a three to four-drug chemotherapy regimen plus 5-fluorouracil (FU)-based radiochemotherapy. Patients and methods: Between December 2000 and October 2003, a total of 86 patients were included in both studies. Patients with completely resected gastric adenocarcinoma including a DI or D2 lymph node dissection (LND) were eligible. Treatment consisted of two cycles of folinic acid 500 mg/m(2), 5-FU 2000 mg/m(2) continuous infusion over 24h once weekly for 6 consecutive weeks, paclitaxel 175 mg/m(2) in weeks 1 and 4 and cisplatin 50 mg/m(2) in weeks 2 and 5 (FLPP; n = 4 1) or two cycles of the same 5-FU/folinic acid schedule but with cisplatin 50 mg/m(2) only in weeks 1, 3 and 5 (FLP; n = 45). Radiation with 45 Gy plus concomitantly applied 5-FU 225 mg/m(2)/24 h was scheduled in between the two cycles. Results: Patients characteristics were: D1/D2 LND FLP group 53%/42%; FLPP group 27%/68%; stage distribution: UICC stages III/IV(MO) FLP group 63% and FLPP group 66%. Median follow-up was 10 months (3-25) for FLP and 18 months (2-51) for FLPP patients. CTC grade 3/4 toxicities during the first cycle/chemoradiation/second cycle of FLP: granulocytopenia 3%/0/27%, anorexia 6%/10%/8%; diarrhea 8%/0/4%, nausea 3%/0/4%; FLPP: granulocytopenia 0/0/37%, anorexia 5%/11%/6%; diarrhea 5%/0/3, nausea 3%/8%/0%; early death in one patient due to Pneumocystis carinii pneumonia. Projected 2-year progression-free survival was 64% (95% Cl 56% to 68%) for the FLP and 61% (95% CI 42% to 78%) for the FLPP group. Conclusions: Both chemoradiation regimens appear feasible with an acceptable toxicity profile indicating that cisplatin can be added to 5-FU/FA and that even a four-drug regimen can be investigated further in prospective clinical trials in completely resected gastric cancer patients. Treatment should be given in experienced centres in order to avoid unnecessary toxicity.