Cisplatin-lnduced peripheral neurotoxicity is dependent on total-dose intensity and single-dose intensity

Abstract

The authors prospectively evaluated the effects of three different schedules of cisplatin (DDP) administration in 60 patients with advanced epithelial ovarian cancer. The individual total dose of DDP was 450 mg/m2 in all three groups, and the anti‐cancer response at the end of treatment was similar for the different regimens. The clinical and neurophysiologic results confirmed that axonal sensory neuropathy occurred after the standard administration of DDP (75 mg/m2 in 3‐week cycles) and probably not only the peripheral, but also the central sensory pathway, was involved. Although the total dose of the drug was identical, the two less conventional schedules were less neurotoxic. These results suggest that not only the total‐dose intensity, but also the single‐dose intensity are relevant in the onset of DDP‐induced sensory neuropathy; therefore, the use of less neurotoxic schedules may prevent or reduce sensory nerve damage.

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

“…Neurotoxicity was found to be acceptable with weekly cisplatin chemotherapy. According to previous studies, neurotoxicity is mainly related to cumulative cisplatin dose, and shortening of the treatment interval does not necessarily lead to worsening of the neurotoxic side effects (Cavaletti et al, 1992;Hilkens et al, 1994Hilkens et al, , 1995. Neurotoxicity was evaluated during and immediately following the weekly cisplatin regimen.…”

“…Both paclitaxel and cisplatin are neurotoxic agents, and a combination of cisplatin with taxanes is known to result in increased neurotoxicity (Connelly et al, 1996;Hilkens et al, 1997). Furthermore, cisplatin-induced neurotoxicity is mainly dependent on the cumulative cisplatin dose (Cavaletti et al, 1992;Hilkens et al, 1994Hilkens et al, , 1995. However, despite an increased risk of neurotoxicity in the platinum pretreated patients, severe neurotoxicity necessitating treatment discontinuation rarely occurred.…”

Cisplatin neurotoxicity in the treatment of metastatic germ cell tumour: time course and prognosis

“…Certainly when 4 cycles of BEP chemotherapy are compared with 3 in large numbers of patients, the incidence of sensory symptoms is significantly higher (de Wit et al, 2001). The role of dose intensity has been studied (Cavaletti et al, 1992;Hilkens et al, 1995), but its significance is still unresolved.…”

“…Nerve conduction studies, looking at both conduction velocities and action potentials, are also commonly performed (e.g. Cavaletti et al, 1992). We therefore performed a prospective longitudinal study on men undergoing chemotherapy for metastatic germ cell tumour to determine the incidence, time course and reversibility of neurotoxicity.…”

A phase I study in paediatric patients to evaluate the safety and pharmacokinetics of SPI-77, a liposome encapsulated formulation of cisplatin

“…The clinical application of cisplatin is predominantly limited by the considerable side effects of cisplatin treatment, which include acute toxicity such as nausea and vomiting and chronic side effects of nephrotoxicity, ototoxicity and neurotoxicity (Krakoff, 1979;Vermorken et al, 1983;Cavaletti et al, 1992). While the search for superior platinum drugs continues, it is essential that methods are investigated to optimize the current clinical use of cisplatin in both paediatric and adult patient populations.…”