PURPOSE: To review the pharmacodynamics, pharmacokinetics, toxicities, and relative clinical activities of cisplatin and carboplatin. Through a search of the MEDLINE database, we identified phase III clinical trials and pharmacologic studies comparing cisplatin and carboplatin published in the English language medical literature from January 1966 to December 1997. RESULTS: Prospective randomized trials comparing cisplatin to carboplatin were identified for ovarian (n = 12), germ cell (n = 4), non–small-cell lung (n = 1), small-cell lung (n = 3), and head and neck (n = 4) cancers. Carboplatin and cisplatin were equally effective in suboptimally debulked ovarian cancer and extensive-stage small-cell lung cancer. One study each showed a trend toward better survival in favor of cisplatin for patients with optimally debulked ovarian and limited-stage small-cell lung cancers. These results were, however, based on subset analyses. In germ cell tumors, carboplatin was inferior because of lower relapse-free surviv...

Review of the Comparative Pharmacology and Clinical Activity of Cisplatin and Carboplatin

The data base for rational guidelines to safe, efficacious drug prescribing in adults with renal insufficiency are presented in tabular form. Current medical literature was extensively surveyed to provide as much specific information as possible. When information is lacking, however, recommendations are based on pharmacokinetic variables in normal subjects. Nephrotoxicity, important adverse effects, and special considerations in renal patients are noted. Adjustments are suggested for hemodialysis and peritoneal dialysis when appropriate.

https://www.ajkd.org/article/S0272-6386(83)80060-2/pdf

Drug Prescribing in Renal Failure: Dosing Guidelines for Adults

Uremia affects every organ system and every aspect of drug disposition by the body. Because the kidney is the major regulator of the internal fluid environment, the physiologic changes associated with renal disease have pronounced effects on the pharmacology of many drugs. Containing information on over 450 drugs, the fifth edition of "Drug Prescribing in Renal Failure" is the most extensive collection of drug-dosing information ever published for patients with impaired renal function. Factors for determining drug dosage are given in easy-to-read tables. This edition contains additional recommendations for supplemental drug dosing during renal replacement therapies and an expanded section on antimicrobial agents that includes many new antiviral agents used in the treatment of HIV infection. "Drug Prescribing in Renal Failure" is a comprehensive guide to understanding the biochemical and physiologic effects of drugs in patients with renal disease.

Drug prescribing in renal failure : dosing guidelines for adults and children

Cisplatin is a platinum chemotherapeutic used in a variety of malignancies. The antineoplastic activity occurs from DNA cross-links and adducts, in addition to the generation of superoxide radicals. Nephrotoxicity is the most well-known and potentially most clinically significant toxicity. Unfortunately, the mechanism for cisplatin nephrotoxicity has not been completely elucidated; however, many theories have been developed. Other toxicities include gastrointestinal, myelosuppression, ototoxicity and neurotoxicity. Saline diuresis is currently the most accepted way to prevent cisplatin nephrotoxicity. Research has focused on pharmaceuticals and enzyme/molecular alterations as alternatives to long-term diuresis. No agents have currently been identified that can protect from all toxicities. Cisplatin has shown activity against osteosarcoma, transitional cell carcinoma, squamous cell carcinoma (SCC), melanoma, mesothelioma, carcinomatosis and germinal cell tumours in the dog. In the cat, cisplatin cannot be utilized because of fulminant pulmonary oedema that occurs at standard doses. Intralesional cisplatin has been utilized in horses for the treatment of SCC and sarcoids.

Cisplatin: a review of toxicities and therapeutic applications.

Ten of 11 patients with ovarian cancer receiving cisplatin developed a distal sensory neuropathy, manifested early by decreased vibratory sensibility in toes and depressed ankle jerks and later by uncomfortable paresthesias. Eleven patients receiving cisplatin, 50 mg/m2 monthly (mean tstal, 580 mg/m2) were studied prospectively with monthly neurologic examinations and conduction velocity determinations of median, peroneal, and sural nerves. Early signs were decreased vibratory sensibility in toes (mean dose, 417 f 132 mg/m2 [SD]) and loss of ankle jerks (mean dose, 455 f 86 mg/m2). With continued therapy, four developed paresthesias. Strehgth was Unaffected. Sural nerve responses abruptly disappeared in six patients (mean dose, 383 +- 103 mg/m2). Other conduction velocities remain4 sormal. Electron microscopy of peripheral nerves from four patients showed axonal degeneration and secondary myelin breakdown. Platinum concentrations in three patients were similar in tumor (3.3 fig/&, sural nerves (3.5 fig/g), and spinal ganglia (3.8 pg/g), but lower in brain (0.17 fig/&. This may explain the cisplatin toxicity of peripheral nerves with relative sparing of the central nervous system. Cancer 54:1269-1275, 1984. isDiAMiNE DICHLOROPLATINU~~ (cisplatin) has been C used as a cancer chemotherapeutic agent since I 972'.2 and has shown particular efficacy against ovarian, testicular, and bladder cancer^.^ The principle side effects are nephrotoxicity, ototoxicity, nausea and vomiting, and myelos~ppression.~ Scattered reports of peripheral neuropathy associated with cisplatin therapy also have ap~eared.~-'~ The neuropathy was primarily sensory and often the initial symptoms were paresthesias in the feet.4.5.9.10.12.14.15 Mild motor involvement was present in some case^.^.^.' Although most patients improved with cessation of treatment,4,5*10.1 '*13*18 some progressed to severe di~ability.~.~ Previous nerve conduction studies have suggested greater involvement of sensory nerves than motor newes.4.5.9.10.14 Sural nerve biopsies revealed changes interpreted as destruction of myelin in five and

Cisplatin neuropathy. Clinical, electrophysiologic, morphologic, and toxicologic studies

The dose-limiting toxic effect of high-dose (100 mg/m2) cisplatin is renal insufficiency. Hydration with furosemide- or mannitol-induced diuresis has been reported to ameliorate this toxicity. Animal studies suggest that mannitol may be superior to furosemide in this regard. Twenty-two patients with advanced neoplasms refractory to conventional therapy were treated with cisplatin at a dose of 100 mg/m2 every 21--28 days. Patients were randomized to receive 37.5 g of mannitol by 6-hour infusion with cisplatin or 40 mg of furosemide prior to cisplatin therapy. Hydration with at least 1 liter of normal saline was given prior to cisplatin. Nephrotoxicity (creatinine greater than 2 mg/100 ml, creatinine clearance greater than 50 ml/minute) occurred in 19% of courses in the furosemide-treated group and in 28% of courses in the mannitol-treated group. Peak plasma platinum concentration, terminal half-life, urinary excretion, and percent protein-bound plasma platinum were similar in both groups. The use of cisplatin at this dose schedule resulted in similar toxicity and pharmacokinetics when using hydration with either furosemide or mannitol.

High-dose cisplatin therapy using mannitol versus furosemide diuresis: comparative pharmacokinetics and toxicity

Two cases of apparent ophthalmologic toxicity which occurred during treatment with cis-dichlorodiammineplatinum(II) (DDP) are described. In the first case, a patient with testicular carcinoma developed papilledema after three courses of DDP and adriamycin therapy. In the second case, a patient with breast cancer developed retrobulbar neuritis after three courses of DDP therapy. The differential diagnosis and possible explanation for these toxic effects are discussed.

Ophthalmologic toxicity after cis-dichlorodiammineplatinum(II) therapy.

Cis-Dichlorodiammine platinum (DDP) 75 mg/m2 on days 1 and 8 and Adriamycin (ADR) 60 mg/m2 on day 1 were used in 31 patients with advanced gynecological and genitourinary neoplasms. The DDP was given by 6 hours intravenous infusion with 2 liters of 5% Dextrose and 0.5 normal saline using Mannitol and/or furosemide diuresis. Courses were repeated every 21 to 28 days. Responses were seen in 7 of 8 patients with germinal cell neoplasms (5 complete, 2 partial) with a median duration of eight months. A partial response was obtained in 3 of 7 patients with bladder carcinoma with a median duration of three months. There were four partial responses obtained in 9 patients with ovarian carcinoma with a median duration of five months. Toxicities included nausea and vomiting in all 31 patients, nephrotoxicity (serum creatinine > 2 g/100 ml) in patients, tinnitus and/or high frequency hearing loss in 10 patients, and neurotoxicity (peripheral neuropathy, normal pressure hydrocephalus, papilledema) in 8 patients. Severe leukopenia (WBC < 2000/cu mm) and thrombocytopenia (< 100,000/cu mm) occurred in 25% and 45% of evaluable courses, respectively and necessitated dosage reduction in all and delay of therapy in some patients. Peak plasma Pt levels were 2.61 +/- .18 microgram/cc on day 1 and 3.52 +/- .39 microgram/cc on day 8 with a longer terminal half-life on day 8 (252 hours) compared to day 1 (156 hours). Peak plasma ADR levels ranged from .53 to 1.67 N moles/cc with an average terminal half-life of 22.8 hours. This agrees with values of ADR when given alone. This dose and schedule of DDP-ADR is active against advanced gynecological and genitourinary neoplasms, but the amount of toxicity seen indicates that modifications will have to be made.

Cis‐dichlorodiammine platinum and adriamycin therapy for advanced gynecological and genitourinary neoplasms

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High-dose cisplatin therapy using mannitol versus furosemide diuresis: comparative pharmacokinetics and toxicity

Ophthalmologic toxicity after cis-dichlorodiammineplatinum(II) therapy.

Cis‐dichlorodiammine platinum and adriamycin therapy for advanced gynecological and genitourinary neoplasms