Weekly high-dose cisplatin is a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients

Abstract

In the present study we describe the toxicity of weekly high-dose (70 -85 mg m À2 ) 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 4grade 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 highdose cisplatin administered in hypertonic saline is a feasible treatment regimen.

Usefulness of Pseudocontinuous Arterial Spin-Labeling for the Assessment of Patients with Head and Neck Squamous Cell Carcinoma by Measuring Tumor Blood Flow in the Pretreatment and Early Treatment Period

“…[8][9][10][11] However, this method is somewhat invasive and requires IV placement and contrast injection, and repetitive scanning is sometimes difficult, especially during chemotherapy when renal dysfunction frequently occurs (approximately 25%-42%) in patients given cisplatin. 12,13 Because of the difficulties of repetitive scanning, there have been few studies of the changes in TBF with repetitive scanning over the treatment period, and the number of patients in these reports is quite small, at 10 to Ͻ20 patients. [14][15][16] Thus, the role and potential of TBF measurement during treatment remain unclear.…”

Activation of Lipopolysaccharide–TLR4 Signaling Accelerates the Ototoxic Potential of Cisplatin in Mice

“…Thereafter, various target genes, including those producing inflammatory cytokines, are regulated. TLR4 is the most well-characterized TLR: it is localized on the cell surface and acts as the receptor for bacterial endotoxins, such as LPS (14,15), a cell wall component of Gramnegative bacteria that is known to induce immune activation. LPS is composed of lipid A, O-Ag, and core oligosaccharide.…”

Risk Factors Associated with Cisplatin-Induced Nephrotoxicity in Patients with Advanced Lung Cancer

“…The main risk factors for CIN such as older age, female gender, smoking, hypoalbuminemia, diabetes mellitus, and cardiovascular disease have been extensively studied. 10,17,24) However, these risk factors are not considered when making clinical decisions about treatment continua- 14) Differences in continuous data were compared using the Mann-Whitney U-test. * Significance level was set at p<0.05. tion, because they are non-numerical objective phenomena and cannot be used for treatment planning.…”

“…8) Despite these approaches, cisplatin-induced nephrotoxicity (CIN) still occurs. [9][10][11] The ability to identify patients at risk for nephrotoxicity would improve the efficacy and safety of CDDP. Although the risk factors for CIN have been extensively investigated and many factors have been reported, [12][13][14][15] CIN prevention methods are not 100% successful.…”