Renal toxicity of adjuvant chemoradiotherapy with cisplatin in gastric cancer.
OBJECTIVE
Adjuvant, 5-fluorouracil (5-FU)-based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function.


METHODS
Between December 2000 and September 2003, 27 patients were treated at Tübingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m2), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m2/24 h). A dose constraint of <or=12 Gy for 37.5% of the functional volume of both kidneys was used. Renal function was assessed by the changes in creatinine and creatinine clearance during follow-up.


RESULTS
The prescribed 45 Gy was administered to 100% of the patients, and the cumulative cisplatin dose was 200 mg/m2 in 74% of all patients. In 89%, the constraints concerning the renal absorbed doses were met. The median follow-up for the creatinine and clearance values was 30 and 26 months, respectively. The creatinine values tended to worsen over time without reaching critical levels. We were unable to demonstrate a significant dose-response relationship for renal damage in the tested dose range.


CONCLUSIONS
Using a dose constraint of <or=12 Gy for 37.5% of the functional volume of both kidneys appears to be safe at a median follow-up of 2 years for a cumulative cisplatin dose of 200 mg/m2 administered before and after simultaneous 5-FU and radiotherapy.
Welz
Stefan
S
Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany. stefan.welz@med.uni-tuebingen.de
Hehr
Thomas
T
Kollmannsberger
Christian
C
Bokemeyer
Carsten
C
Belka
Claus
C
Budach
Wilfried
W
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D004943:Esophagogastric Junction; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000528:radiation effects*; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
D015415:Biomarkers; D003404:Creatinine; D017239:Paclitaxel; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil