Residual chromosomal damage after radiochemotherapy with and without amifostine detected by 24-color FISH.
BACKGROUND
Amifostine is a radioprotective drug applied to reduce acute radiation toxicity during a course of conventionally fractionated radiotherapy. In the present study, amifostine was used in patients undergoing adjuvant radiochemotherapy for rectal cancer. It was described previously that additional application of amifostine led to less acute skin and bowel toxicity. The present study was aimed to determine whether amifostine has an influence on the amount of residual chromosomal damage.


METHODS
Peripheral lymphocytes of twelve rectal cancer patients who had undergone postoperative radiochemotherapy 2-3 years ago were investigated for residual chromosomal damage using 24-color fluorescence in situ hybridization (24-color FISH). All twelve patients had received a total dose of 55.8 Gy in conventional fractionation of 1.8 Gy and a 120-h continuous infusion of 5-fluorouracil (5-FU) chemotherapy (1,000 mg/m(2) per day) in the 1st and 5th week of irradiation. Seven out of twelve patients had been given additional amifostine on chemotherapy days (500 mg total dose as short i.v. infusion immediately prior to the daily radiation fraction). Cultivation of lymphocytes and 24-color FISH were performed according to standard protocols. 100 metaphases per patient were analyzed for chromosomal aberrations in a blind study.


RESULTS
Analysis of the average number of breaks per mitosis (B/M) revealed an increased amount of residual chromosomal damage in the group treated with amifostine (0.65 B/M [0.32-0.97]) as well as in those treated without amifostine (0.76 B/M [0.31-1.25]). Also the average number of cells containing aberrations per 100 analyzed metaphases was similar (with amifostine: 22.1 [13-32] vs. 24.4 [13-35] without amifostine). The aberration types, occurring as simple translocations, reciprocal translocations, breaks, dicentrics, inversions, rings and complex chromosomal rearrangements, did not show any specific accumulation in one or the other group either.


CONCLUSIONS
While there was a significant amifostine-mediated clinical amelioration of normal tissue toxicity, the comparison of residual chromosomal damage 2-3 years after completion of radiochemotherapy was characterized by a high interindividual variation, and no equivalent difference could be detected between the two groups.
Kuechler
Alma
A
Department of Radiation Oncology, Friedrich Schiller University, Jena, Germany. almu@mti.uni-jena.de
Dreidax
Mareike
M
Pigorsch
Steffi U
SU
Liehr
Thomas
T
Claussen
Uwe
U
Wendt
Thomas G
TG
Dunst
Jürgen
J
D000368:Aged; D004999:Amifostine / Q000008:administration & dosage* / Q000009:adverse effects; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D002869:Chromosome Aberrations; D020223:Chromosome Painting; D003131:Combined Modality Therapy; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects*; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery
D000964:Antimetabolites, Antineoplastic; D011837:Radiation-Protective Agents; D004999:Amifostine; D005472:Fluorouracil