Cisplatin neurotoxicity: the relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity.

Gregg, Richard; Molepo, J. M.; Monpetit, V J; Mikael, N Z; Redmond, Daniel P.; Gadia, Maria T.; Stewart, David J.

doi:10.1200/jco.1992.10.5.795

Cited by 333 publications

(207 citation statements)

References 25 publications

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“…It may be that the elimination half-life of platinum in neural tissue is less than 12 days and that steady-state concentrations had already been reached before 8 weeks. Gregg et al (1992), studied platinum concentrations in neurological tissue taken after death from cisplatin-treated humans and described a relationship between the tissue accumulation of platinum and peripheral neurotoxicity (Gregg et al, 1992). As in our study, they found preferential distribution of platinum to peripheral vs central nervous tissues, but tissue levels were two-to fourfold higher than in our rats even though we used more toxic platinum derivatives.…”

Section: Discussionmentioning

confidence: 44%

Stereoselective peripheral sensory neurotoxicity of diaminocyclohexane platinum enantiomers related to ormaplatin and oxaliplatin

Screnci

Er²,

Hambley³

et al. 1997

Br J Cancer

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Summary The diaminocyclohexane platinum (Pt(DACH)) derivatives ormaplatin and oxaliplatin have caused severe and dose-limiting peripheral sensory neurotoxicity in a clinical trial. We hypothesized that this toxicity could vary in relation to the biotransformation and stereochemistry of these Pt(DACH) derivatives. We prepared pure R,R and S,S enantiomers of ormaplatin (Pt(DACH)CI4). oxaliplatin (Pt(DACH)oxalato) and their metabolites (Pt(DACH)CI2 and Pt(DACH)methionine) and assessed their peripheral sensory neurotoxicity and tissue distribution in the rat and in vitro anti-tumour activity in human ovarian carcinoma cell lines. The R,R enantiomers of Pt(DACH)CI4, Pt(DACH)oxalato and Pt(DACH)CI2, induced peripheral sensory neurotoxicity at significantly lower cumulative doses (18 ± 5.7 vs 32 ± 2.3 imol kg-1; P < 0.01) and at earlier times (4 ± 1 vs 6.7 ± 0.6 weeks; P = 0.016) during repeat-dose treatment than the S,S enantiomers. Pt(DACH)methionine enantiomers showed no biological activity. There was no difference between Pt(DACH) enantiomers in the platinum concentration in sciatic nerve, dorsal root ganglia, spinal cord, brain or blood at the end of each experiment. Three human ovarian carcinoma cell lines (41 M, 41 McisR and SKOV-3) showed no (or inconsistent) chiral discrimination in their sensitivity to Pt(DACH) enantiomers, whereas two cell lines (CH-1 and CH-1 cisR) showed modest enantiomeric selectivity favouring the R,R isomer (more active). In conclusion, Pt(DACH) derivatives exhibit enantiomeric-selective peripheral sensory neurotoxicity during repeated dosing in rats favouring S,S isomers (less neurotoxic). They exhibited less chiral discrimination in their accumulation within peripheral nerves and in vitro anti-tumour activity.

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Section: Discussionmentioning

confidence: 44%

Stereoselective peripheral sensory neurotoxicity of diaminocyclohexane platinum enantiomers related to ormaplatin and oxaliplatin

Screnci

Er²,

Hambley³

et al. 1997

Br J Cancer

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“…The main neuropathy of CDDP is sensory peripheral neuropathy (van der Hoop et al, 1990;Gregg et al, 1992). A delay in SNCV due to the injury of dorsal root ganglia and peripheral nerve has previously been reported in rats given CDDP, although MNCV was preserved in the tail and hind paws of rats (McKeage et al, 1994;Tredici et al, 1998;Meijer et al, 1999;Tredici et al, 1999).…”

Section: Discussionmentioning

confidence: 95%

Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats

et al. 2005

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In spite of the clinical usefulness of cisplatin (CDDP), there are many occasions in which it is difficult to continue the administration of CDDP due to its nephrotoxicity and neurotoxicity. We examined the incorporation of CDDP into polymeric micelles to see if this allowed the resolution of these disadvantages. Cisplatin was incorporated into polymeric micelles through the polymer -metal complex formation between polyethylene glycol poly(glutamic acid) block copolymers and CDDP (NC-6004). The pharmacokinetics, pharmacodynamics, and toxicity studies of CDDP and NC-6004 were conducted in rats or mice. The particle size of NC-6004 was approximately 30 nm, with a narrow size distribution. In rats, the area under the curve and total body clearance values for NC-6004 were 65-fold and one-nineteenth the values for CDDP (Po0.001 and 0.01, respectively). In MKN-45-implanted mice, NC-6004 tended to show antitumour activity, which was comparable to or greater than that of CDDP. Histopathological and biochemical studies revealed that NC-6004 significantly inhibited the nephrotoxicity of CDDP. On the other hand, blood biochemistry revealed transient hepatotoxicity on day 7 after the administration of NC-6004. Furthermore, rats given CDDP showed a significant delay (Po0.05) in sensory nerve conduction velocity in their hind paws as compared with rats given NC-6004. Electron microscopy in rats given CDDP indicated the degeneration of the sciatic nerve, but these findings were not seen in rats given NC-6004. These results were presumably attributable to the significantly reduced accumulation of platinum in nerve tissue when NC-6004 was administered (Po0.05). NC-6004 preserved the antitumour activity of CDDP and reduced its nephrotoxicity and neurotoxicity, which would therefore seem to suggest that NC-6004 could allow the long-term administration of CDDP where caution against hepatic dysfunction must be exercised.

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“…11 At least in some of these manifestations, there is an association with the finding of high levels of tissue platinum in the brain. 12 Chemotherapy-induced cerebral abnormalities occur in a wide variety of settings and present with a wide range of clinical findings. Neurologic complications have been described with antineoplastic drugs including alkylating agents, antimetabolites, periwinkle derivatives and other agents including cisplatin and L-asparaginase.…”

Section: Discussionmentioning

confidence: 99%

Fatal chemotherapy-induced encephalopathy following high-dose therapy for metastatic breast cancer: a case report and review of the literature

Cossaart

SantaCruz

Preston

et al. 2003

Bone Marrow Transplant

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Summary:Chemotherapy-induced encephalopathies occur in a variety of clinical settings and the most detailed accounts have been described following combination methotrexate and radiation therapy. The case described herein developed severe encephalopathy following a high-dose chemotherapy protocol used in the treatment of metastatic carcinoma of the breast. Visual symptoms developed 3 weeks after completing high-dose chemotherapy and peripheral blood hematopoietic stem cell transplantation. Over the next several weeks, additional neurologic deficits developed and continued to progress despite various treatment interventions. Diffuse deep gray matter damage was identified on MR imaging and a brain biopsy revealed pathological findings similar in many respects to those described for methotrexate/radiation, cisplatin, BCNU and/or 5 FU/levamisole-related leukoencephalopathy. The patient succumbed to complications resulting from the CNS disorder, 8 weeks after the onset of symptoms. This case is unusual for two reasons. First, the patient developed severe encephalopathy following a high-dose chemotherapy protocol commonly used in the treatment of metastatic breast carcinoma and second, the encephalopathy involved primarily deep gray matter structures rather than white matter.

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Cisplatin neurotoxicity: the relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity.

Cited by 333 publications

References 25 publications

Stereoselective peripheral sensory neurotoxicity of diaminocyclohexane platinum enantiomers related to ormaplatin and oxaliplatin

Stereoselective peripheral sensory neurotoxicity of diaminocyclohexane platinum enantiomers related to ormaplatin and oxaliplatin

Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats

Fatal chemotherapy-induced encephalopathy following high-dose therapy for metastatic breast cancer: a case report and review of the literature

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