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.


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 D1 or D2 lymph node dissection (LND) were eligible. Treatment consisted of two cycles of folinic acid 500 mg/m2, 5-FU 2000 mg/m2 continuous infusion over 24 h once weekly for 6 consecutive weeks, paclitaxel 175 mg/m2 in weeks 1 and 4 and cisplatin 50 mg/m2 in weeks 2 and 5 (FLPP; n=41) or two cycles of the same 5-FU/folinic acid schedule but with cisplatin 50 mg/m2 only in weeks 1, 3 and 5 (FLP; n=45). Radiation with 45 Gy plus concomitantly applied 5-FU 225 mg/m2/24 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(M0) 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% CI 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.
Kollmannsberger
C
C
Department of Hematology/Oncology, Department of Radiation Oncology, University of Tuebingen, Tuebingen.
Budach
W
W
Stahl
M
M
Schleucher
N
N
Hehr
T
T
Wilke
H
H
Schleicher
J
J
Vanhoefer
U
U
Jehle
E C
EC
Oechsle
K
K
Trarbach
T
T
Boehlke
I
I
Kanz
L
L
Hartmann
J T
JT
Bokemeyer
C
C
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D015996:Survival Rate
D017239:Paclitaxel; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil