Carboplatin nephrotoxicity

Carboplatin (96) is significantly less toxic in the clinic than cisplatin. Most particularly, it is much less nephrotoxic. Use of a bidentate ligand also ensures formation of a ds complex. Its synthesis begins with cis-diammine platinum diiodide (94) which is reacted with silver sulfate to give cis-diaquodiam mine platinum sulfate (95). This is reacted with the barium salt of 1,1-cyclo-butanedicarboxylic acid to yield carboplatin [23],... 

Carboplatin Myelosuppression (DLT), nephrotoxicity, nausea/ vomiting, electrolyte wasting, diarrhea, stomatitis, hypersensitivity reactions Prehydration not required. Give proper dosing for renal dysfunction. Premedicate dexamethasone, diphenhydramine, and cimetidine. 

The second criteria, a different activity spectrum, is met by oxaliplatin (Figure 1.9A), the l isomer of [oxalatol f ra/rv-1,2-diaminocyclohexane)platinum (II)], oxaliplatin, [Pt(II)(oxalato)(DACH)]. This platinum agent is used for secondary treatment of metastatic colorectal cancer.77 Oxaliplatin, like carboplatin, has a kinetically slower leaving group, and is also less nephrotoxic than cisDDP. The limiting toxicity of oxaliplatin is peripheral sensory neuropathy, also seen with cisDDP. The neuropathy affects the extremities and increases in incidence and... 

Oxaliplatin is a newer platinum-based agent. It is most frequently administered in combination with fluorouracil and leucovorin for the treatment of colorectal cancer. Oxaliplatin has less ototoxicity and nephrotoxicity than cisplatin and carboplatin. 

Carboplatin is a promising second-generation platinum agent. Because it is less reactive, it causes less nephrotoxicity, myelosuppression, and thrombocytopenia. 

Carboplatin is substantially simpler to administer. Extensive hydration is not required because of the lack of nephrotoxicity at standard doses [215], Carboplatin is reconstituted in chloride-free solutions (chloride can displace the leaving groups), and administered over 30 minutes as a rapid intravenous infusion. Carboplatin has been incorporated in high-dose chemo-... 

Increased nephrotoxicity with cidofovir, aminoglycosides, carboplatin, cisplatin, clofarahine, efavirenz/emtricitahine/tenofovir, gallium, tenofovir... 

The nephrotoxic and ototoxic effects of cisplatin and carboplatin can be potentiated by concurrent administration of aminoglycosides, as shown in animals (179). 

In patients with ovarian cancer, the combination of inter-leukin-3 with high-dose carboplatin was poorly tolerated severe fever, malaise, protracted nausea, vomiting, severe hypotension, and nephrotoxicity required withdrawal of interleukin-3 in 60% of patients when interleukin-3 was given only 24 hours after high-dose carboplatin (18). 

The negligible nephrotoxicity of oxahplatin and carboplatin compared with cisplatin may be related to their slower rates of conversion to reactive species. As a result, intensive hydration is not warranted during carboplatin or oxaliplatin infusion, in contrast to cisplatin (1,8-10). In the case of macromolecular platinum-protein complex formation, decomposition proceeds rather slowly, which may explain why the urinary excretion of total platinum is increased for a long time after treatment, particularly in patients who have been given cisplatin (19,20). 

Like carboplatin, oxaliplatin does not usually cause nephrotoxicity. In addition, both drugs are only moderately emetogenic, in contrast to cisplatin. The most important dose-limiting adverse effect of oxaliplatin is a sensory peripheral neuropathy, which has two different forms ... 

A patient with no other risk factors developed irreversible nephrotoxicity after four cycles of carboplatin 300 mg/m and methotrexate 50 mg/m (278). This appears to have been an additive effect of drugs that are not individually nephrotoxic until much higher doses. 

English MW, Skinner R, Pearson AD, Price L, Wyllie R, Craft AW. Dose-related nephrotoxicity of carboplatin in children. Br J Cancer 1999 81(2) 336 1. 

Experience with ifosfamide-contain-ing regimens has revealed a consistent clinical pattern of nephrotoxicity. Fanco-ni syndrome, which is characterized by acid, sodium, potassium, magnesium, and small molecular weight proteins, occurs in 1-5% of the children who have received repeated treatments of ifosfamide [94] [95]. In fact the development of rickets secondary to Fanconi syndrome has been reported following treatment with ifosfamide [96]. Patients who have received therapy with cisplatin or carboplatin in addition to ifosfamide may be at greater risk for development of Fanconi syndrome [97]. Hemorrhagic cystitis is a significant toxicity that occurs with ifosfamide administration [98,... 

Bregman CL, Williams PD. Comparative nephrotoxicity of carboplatin and cisplatin In combination with actinomycin. Cancer Chemother Pharmacol 1986. 

---