Cumulative prior dose of cisplatin as a cause of the nephrotoxicity of high-dose chemotherapy followed by autologous stem-cell transplantation.
BACKGROUND
Nephrotoxicity is one of the most frequent dose-limiting factors of high-dose chemotherapy to create tolerance of autologous peripheral blood stem-cell transplantation (PBSCT) for the treatment of malignant diseases. The relative importance of factors that may be responsible for the development of nephrotoxicity varied in different trials.


METHODS
The factors affecting nephrotoxicity in the early period of high-dose ifosfamide, carboplatin and etoposide treatment (ICE) followed by autologous PBSCT was investigated in 47 patients. ICE was given as a conditioning regimen for 6 days. Nephrotoxicity was defined as an increase in the serum creatinine concentration of 0.5 mg/dl or more over individual baseline levels.


RESULTS
Eleven patients developed nephrotoxicity (23.4%). There was no significant difference in baseline renal function between patients with nephrotoxicity and those without. No differences were found between the two groups in terms of average total doses of ICE, infections and antibiotic use. The age of patients was higher in those with nephrotoxicity (37+/-3.7 vs 26+/-1.7 years, P=0.019). The cumulative cisplatin dose administered prior to this regimen was higher in the group that developed nephrotoxicity (470 vs 227 mg/m(2), P=0.02). The overall mortality rate was 17%, but the transplant-related deaths were higher in the presence of nephrotoxicity (54.5 vs 5.5%, P=0.001).


CONCLUSIONS
The cumulative dose of cisplatin is a strong risk factor for the development of nephrotoxicity in patients who receive high doses of ICE followed by PBSCT. Nephrotoxicity may occur with much lower doses than the currently recommended maximum doses.
Caglar
Kayser
K
Division of Nephrology, Department of Medicine and. Division of Medical Oncology, Gülhane Medical School, Etlik, Ankara, Turkey. kaysercaglar@hotmail.com
Kinalp
Can
C
Arpaci
Fikret
F
Turan
Mustafa
M
Saglam
Kenan
K
Ozturk
Bekir
B
Komurcu
Seref
S
Yavuz
Izzet
I
Yenicesu
Müjdat
M
Ozet
Ahmet
A
Vural
Abdülgaffar
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007239:Infections / Q000150:complications / Q000188:drug therapy; D007674:Kidney Diseases / Q000139:chemically induced* / Q000150:complications / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014182:Transplantation, Autologous
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D016190:Carboplatin; D002945:Cisplatin; D007069:Ifosfamide