Weekly high-dose cisplatin is a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients.
In the present study we describe the toxicity of weekly high-dose (70-85 mg x m(-2)) cisplatin in 400 patients (203 men, 197 women; median age 54 years) with advanced solid tumours treated in the period 1990-2001 who took part in phase I/II trials, investigating the feasibility and efficacy of weekly cisplatin alone, or in combination with paclitaxel or etoposide. Cisplatin was administered in 250 ml NaCl 3% over 3 h, for six intended administrations. The mean number of administrations was 5.3 (range, 1-6 administrations). Reasons not to complete six cycles were disease progression (7.5%), haematological toxicity (9%), nephrotoxicity (7%), ototoxicity (2.5%), neurotoxicity (1%), gastrointestinal toxicity (1%), cardiovascular complications (0.5%) or a combination of reasons including noncompliance and patient's request (5.5%). Logistic regression analysis was used to evaluate baseline parameters for prognostic value regarding toxicity. Leukopenia correlated with etoposide cotreatment, and thrombocytopenia with cisplatin dose and prior (platinum-based) chemotherapy. Risk factors for nephrotoxicity were older age, female gender, smoking, hypoalbuminaemia and paclitaxel coadministration. Neurotoxicity >grade 1 (11% of patients) was associated with prior chemotherapy and paclitaxel coadministration. Symptomatic hearing loss occurred in 15% with anaemia as the predisposing factor. We conclude that weekly high-dose cisplatin administered in hypertonic saline is a feasible treatment regimen.
de Jongh
F E
FE
Department of Medical Oncology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.
van Veen
R N
RN
Veltman
S J
SJ
de Wit
R
R
van der Burg
M E L
ME
van den Bent
M J
MJ
Planting
A S Th
AS
Graveland
W J
WJ
Stoter
G
G
Verweij
J
J
D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D016017:Odds Ratio; D011379:Prognosis; D012189:Retrospective Studies
D002945:Cisplatin