Reduced ability to clear ultrafilterable platinum with repeated courses of cisplatin.

Reece, Phillip A.; Stafford, Irene; Russell, J; Gill, P. Grantley

doi:10.1200/jco.1986.4.9.1392

Cited by 39 publications

(14 citation statements)

References 25 publications

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“…[20] Urinary cisplatin excretion is by glomerular filtration and active renal tubular secretion. [34][35][36] Organic anion and cation transport mechanisms are involved in active renal tubular cisplatin transportP2] Platinum concentrations are higher in the kidney than in plasma or other tissues, particularly in areas of functional and histological damage, i.e. the juxta-medullary region and outer stripe of the medulla.…”

Section: Pathogenesismentioning

confidence: 99%

Comparative Adverse Effect Profiles of Platinum Drugs

1995

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Since the discovery of the biologically active platinum complexes 30 years ago, 2 agents have become widely established in clinical oncology practice. Both cisplatin and carboplatin are platinum(II) complexes with 2 ammonia groups in the cis- position. However, they differ in their solubility, chemical reactivity, dichloride or alicyclic oxygenated leaving groups, pharmacokinetics and toxicology. Cisplatin causes severe renal tubular damage and reduces glomerular filtration, and requires concurrent saline hydration and mannitol diuresis to eliminate potentially lethal and unacceptable damage to the kidneys. Carboplatin, at conventional doses, causes no decrease in glomerular filtration and only minor transient elevations in urinary enzymes. Cisplatin is the most emetic cancer drug in common use, while nausea and vomiting associated with carboplatin are moderately severe. Serotonin release from enterochromaffin gut mucosal cells and stimulation of serotonin 5-HT3-receptors mediates acute emesis. Selective inhibitors of the 5-HT3-receptor protect against cisplatin- and carboplatin-induced nausea and vomiting. Peripheral neurotoxicity is the most dose-limiting problem associated with cisplatin. Loss of vibration sense, paraesthesia and sensory ataxia comes on after several treatment cycles. Carboplatin, however, is relatively free from peripheral neurotoxicity. Audiometry shows cisplatin-induced ototoxicity in 75 to 100% of patients, which may be associated with tinnitus and hearing loss. Ototoxicity is rare with conventional dose carboplatin therapy. Monitoring hearing with audiograms may identify early signs before significant impairment occurs. Cisplatin causes mild haematological toxicity to all 3 blood lineages. Haematological toxicity is dose-limiting for carboplatin, with thrombocytopenia being a greater problem than leucopenia. Although carboplatin is not toxic to the kidney, renal function markedly affects the severity of carboplatin-induced thrombocytopenia. The major clearance mechanism of cisplatin is irreversible binding in plasma and tissues, while carboplatin is cleared by glomerular filtration. Metabolism of cisplatin to aqua, amino acid and protein species is extensive, whereas carboplatin exists mainly as the free unchanged form. Strong relationships between carboplatin renal clearance, glomerular filtration rate, area under the plasma concentration-time curve (AUC) of filterable platinum and severity of thrombocytopenia have prompted dose adjustment according to renal function. New analogues such as JM216 offer the potential advantages of oral administration and few nonhaematological toxicities. Analogues based on the diaminocyclohexane ligand have encountered problematic neurotoxicity.

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Section: Pathogenesismentioning

confidence: 99%

Comparative Adverse Effect Profiles of Platinum Drugs

1995

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“…Recently, there have been efforts to develop an optimal therapeutic schedule of chemotherapeutic agents by investigating the pharmacokinetics/pharmacodynamics (PK/PD) correlation (17,18). Reece et al (19) mentioned that repeated courses of CDDP reduced Ccr and increased free Pt AVe. Several investigators also reported that lower Ccr correlated with higher AVC and platelet reduction by CDDP analogs such as carboplatin or 254-S (20)(21)(22). It is very difficult to discuss the correlation between pharmacokinetic parameters and the pretreatment Ccr in this study, because the number of patients tested was very small (Table 3).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Cisplatin in Combined Cisplatin and 5-Fluorouracil Therapy: A Comparative Study of Three Different Schedules of Cisplatin Administration

Ikeda

Terashima

Kawamura

et al. 1998

Japanese Journal of Clinical Oncology

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Background: Cisplatin is widely used in combination chemotherapy against a variety of tumors; however, the optimal administration schedule of cisplatin is still controversial. To clarify the pharmacokinetic differences according to the administration schedules of cisplatin, we compared three different administration schedules of cisplatin such as single short-term infusion, daily short-term infusion and daily continuous infusion in combination with 5-fluorouracil. Preliminary clinical responses and toxicities were also investigated. Methods: A total of 12 courses in combination of cisplatin and 5-fluorouracil therapy was studied. The schedules of cisplatin tested were as follows: single short-term infusion (80 mg/m 2 , day 1,2 h div., n =4),daily short-term infusion (20mg/m 2 , days 1 to 5, 2 h div., n =4), daily continuous infusion (100 mg/m 2 , 120 h, n = 4). In all schedules, 5-fluorouracil was continuously administered at a dose of 800 mg/m 2/day on days 1 to 5. The area under the time-concentration curve (AUC) and the maximum concentration (C max ) of total and free Pt were investigated. Results: The highest AUC of total and free Pt and the lowest C max of free Pt were observed in the daily continuous infusion (total AUC; 162.53± 18.39~g h/ml, free AUC; 5.50±0.9~g h/ml, free Cmax; 0.07±0.01 Ilg /ml, mean ± SEM).Two patients in the single short-term infusion and one patient in the daily continuous infusion indicated partial responses clinically. No nephrotoxicity or ototoxicity was observed. All toxicities were mild and tolerable in all regimens; however, the incidence of GI toxicity in daily continuous infusion seemed to be relatively higher. Conclusions: Daily continuous infusion of cisplatin gave the best pharmacokinetic results and to evaluate the clinical advantage of this schedule a prospective randomized trial should be conducted with sufficient numbers of patients.

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“…The reason for this might be the decreased creatinine clearance and pretreatment with cisplatin (Reece et al, 1986;Mulder et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of carboplatin at a dose of 750 mg m-2 divided over three consecutive days

Mulder

Vries²,

Uges³

et al. 1990

Br J Cancer

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Summary Pharmacokinetics of the cisplatin analogue carboplatin were studied in patients with disseminated ovarian and testicular cancer. Carboplatin 750 mg m-2 divided over three consecutive days was given as part of an ablative combination regimen followed by autologous bone marrow transplantation. Platinum (Pt) in plasma, plasma ultrafiltrate and urine was determined up to 96 h after the last drug dose by atomic absorption spectrometry. Carboplatin was measured by high performance liquid chromatography. The curves of ultrafiltrated Pt and carboplatin decayed in a bio-exponential way with t1/2 a of respectively 65 and 70 min and t112 P of repectively 378 and 1014 min. The volumes of distribution (Vd,) were 18 and 25 1 m-2, respectively, and total body clearances (CITB) 79 and 65 ml min-m-2. Both curves overlapped when corrected for the Pt content of carboplatin. A diversion with the three-exponential curve of total Pt occurred between 3 and 6 h.

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Reduced ability to clear ultrafilterable platinum with repeated courses of cisplatin.

Cited by 39 publications

References 25 publications

Comparative Adverse Effect Profiles of Platinum Drugs

Comparative Adverse Effect Profiles of Platinum Drugs

Pharmacokinetics of Cisplatin in Combined Cisplatin and 5-Fluorouracil Therapy: A Comparative Study of Three Different Schedules of Cisplatin Administration

Pharmacokinetics of carboplatin at a dose of 750 mg m-2 divided over three consecutive days

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