Renal toxicity of adjuvant chemoradiotherapy with cisplatin in gastric cancer

Int J Radiat Oncol Biol Phys. 2007 Dec 1;69(5):1429-35. doi: 10.1016/j.ijrobp.2007.05.021. Epub 2007 Aug 9.

Abstract

Purpose: 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.

Patients and 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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Biomarkers / blood
  • Chemotherapy, Adjuvant / adverse effects
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Creatinine / blood
  • Esophagogastric Junction
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Kidney / drug effects*
  • Kidney / radiation effects*
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant / adverse effects
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / radiotherapy*

Substances

  • Biomarkers
  • Creatinine
  • Paclitaxel
  • Cisplatin
  • Leucovorin
  • Fluorouracil