Effect of mannitol and plasma on the cytotoxicity of cisplatin

Holdener, Eduard E.; Park, Chan H.; Belt, Robert J.; Stephens, Ronald L.; Hoogstraten, Barth

doi:10.1016/0277-5379(83)90115-3

Cited by 20 publications

(6 citation statements)

References 6 publications

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“…The longer holding time may thus be one of the reasons why gastrointestinal toxicity is more common with high-dose infusion therapy. Since Holdener et al [27] have reported that only the free platinum species is cytotoxic to cells, lowdose daily bolus infusions may be useful in preserving the higher AUC of free platinum, while at the same time reducing the gastrointestinal toxicity. Thus, it can be surmised that low-dose bolus infusions will be as effective against carcinomas as the high-dose infusion therapy.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of cis‐diamminedichloroplatinum (II) given as low‐dose and high‐dose infusions

et al. 1996

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A pharmacokinetic analysis of cis-diamminedichloroplatinum (11) (DDP) was conducted comparing low-dose daily bolus infusions, and high-dose drip infusions. Eight patients with gastric cancer were treated with lowdose daily bolus infusions of DDP to a total daily dose of 75 mg/rn? bid for 5 days. Four patients with esophageal cancer and one patient with gastric cancer were treated with high-dose drip infusions of DDP to a total daily dose of 70-80 mg/m*. Side effects were assessed in all the patients, and the platinum concentration in plasma was determined by an atomic absorption method. The peak plasma concentration (CmaX) and area under the curve (AUC) were calculated in four cases of the low-dose therapy, and three cases of the high-dose therapy. The side effects of DDP were evaluated according to the World Health Organization (WHO) grading, paying particular attention to nausedvomiting, appetite loss, renal toxicity, and bone marrow suppression. The incidence of nausedvomiting and appetite loss was significantly reduced with low-dose daily bolus infusions when compared to the high-dose drip infusions. Bone marrow toxicity and renal toxicity were similar with both administration methods, although hydration was required for the high-dose drip infusions to prevent renal toxicity. The peak plasma concentration (C,,,,) of total and free platinum, and the area under the curve (AUC) of total platinum, were similar with both administration methods, while the AUC of free platinum was higher with the low-dose daily bolus infusions compared to the high-dose drip infusions. The time when the concentration of total platinum was >1 pg per ml (holding time) was significantly longer with the high-dose drip infusions than with the low-dose daily bolus infusions. The present study suggests that low-dose daily bolus infusions of DDP would be useful in reducing gastrointestinal toxicity, without reducing the area under the curve which is important for antitumor activity. 0 1996 Wiley-t.iss, Inc.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of cis‐diamminedichloroplatinum (II) given as low‐dose and high‐dose infusions

et al. 1996

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“…Cisplatin has reduced cytotoxicity when incubated with human serum or plasma due to binding to blood protein and has therefore relatively short effective duration when injected into the blood (7,9). The half-life of non-protein bound cisplatin is less than 30 min in vivo (8).…”

Section: Discussionmentioning

confidence: 99%

Treatment of Lung Cancer with Bronchial Artery Infusion of Cisplatin and Intravenous Sodium Thiosulfate Rescue

et al. 1988

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“…Therefore the lower peak serum level with continuous infusion may seriously hamper the penetration of cisplatin into cerebrospinal fluid and result in failure to reach the threshold concentration of cisplatin necessary for therapeutic activity (9). In addition cisplatin is rapidly bound to serum protein (14), eliminating the active species (15). Continuous infusion leads to almost complete protein binding over the entire 5 day period while bolus infusion allows a much greater amount of filterable cisplatin to be briefly available for potential central nervous system penetration (8).…”

Section: Responsementioning

confidence: 99%

Treatment of Astrocytoma with a 5-Day Cisplatin Infusion

Grunberg¹,

Bertram²,

McDermed³

et al. 1987

Cancer Drug Delivery

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Although cisplatin may have intrinsic activity against astrocytoma, limited penetration into the central nervous system may severely curtail delivery of adequate amounts of drug to the tumor. In an attempt to increase the dose of delivered drug without markedly increasing toxicity, cisplatin was administered by 5-day continuous intravenous infusion at a dose of 28 mg/m2/day (total dose 140 mg/m2) to 15 evaluable patients (5 with astrocytoma Grade III and 10 with astrocytoma Grade IV). Median age was 39 years, median Karnofsky Performance Status was 80%, and all patients had been previously treated with other modalities. One patient (7%) achieved Partial Response as demonstrated by increased strength of paretic extremities, increased Karnofsky Performance Status, and decrease of enhancing tumor mass on CT scan. Although nephrotoxicity was minimal, nausea and vomiting (usually mild) was seen in 14 patients. Myelosuppression was also common (anemia in 7 patients, leukopenia in 4 patients and thrombocytopenia in 3 patients). Ototoxicity was seen in 5 patients and may represent a combined modality toxicity with prior cranial radiotherapy. Routes and schedules which allow a higher peak serum concentration of cisplatin (such as subselective intracerebral artery infusion) may be necessary to achieve greater central nervous system drug penetration and to maximally exploit cisplatin in the treatment of astrocytoma.

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Effect of mannitol and plasma on the cytotoxicity of cisplatin

Cited by 20 publications

References 6 publications

Pharmacokinetics of cis‐diamminedichloroplatinum (II) given as low‐dose and high‐dose infusions

Pharmacokinetics of cis‐diamminedichloroplatinum (II) given as low‐dose and high‐dose infusions

Treatment of Lung Cancer with Bronchial Artery Infusion of Cisplatin and Intravenous Sodium Thiosulfate Rescue

Treatment of Astrocytoma with a 5-Day Cisplatin Infusion

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