Cisplatin side effects

While carboplatin has the same mechanism of action as cisplatin, it has a much less toxic side-effect profile than cisplatin. The pharmacokinetics of carboplatin are best described by a two-compartment model, with an a half-life of 90 minutes and a terminal half-life of 180 minutes. Carboplatin is eliminated almost entirely by the kidney by glomerular filtration and tubular secretion. Many chemotherapy regimens dose carboplatin based on an area under the curve (AUC), which is referred to... 

THC is effective in several chemotherapy regimens, including methotrexate and the doxorubicin/cyclophosphamide/fluorouracil combination. Cisplatin treatment, however, is more resistant. Side effects of THC are generally well tolerated, and use may be limited in the elderly or with higher doses. Nabilone is a synthetic cannabinoid that is more effective than prochlorperazine in chemotherapy-induced emesis, including cisplatin. Its side effects are similar to THC. Levonantradol is another synthetic cannabinoid with antiemetic effects, and may be administered orally or intramuscularly. The side effect of dysphoria may limit its use. 

Platinum is a relatively rare earth metal usually found with related metals osmium and iridium. While it has a number of industrial applications, its common consumer application is in catalytic converters. This application has actually increased platinum concentrations in roadside dust. The ability of platinum and its derivatives to kill cells or inhibit cell division was discovered in 1965. Platinum-based drugs, such as cisplatin, are used to treat ovarian and testicular cancer, and cancers of the head and neck, as well as others. Unfortunately, the toxic side effects of these agents often limit their usefulness. 

Other potential radiation sensitizers for cervical cancer are being explored in phase I and II trials. Paclitaxel has been combined with cisplatin in several small phase I studies. Pignata et al. (29) found that 50 mg/m2 per week of paclitaxel could be combined with weekly cisplatin (30 mg/m2) and radiation therapy with acceptable toxicity, although 10 of 18 patients in their study had grade 3-4 hematologic toxicity. Chen etal. (30) also were able to give weekly paclitaxel at a dose of 50 mg/m2 (in this case combined with 50 mg/m2 of cisplatin every three weeks) with tolerable toxicity and minimal delay in planned radiation therapy. In both studies, the dose-limiting side effect appeared to be diarrhea. It should be noted that the total dose of cisplatin delivered in these trials was lower than that used in the most successful prospective trials of cisplatin or cisplatin and fluorouracil (Table 3). 

Muderspach et al. (31) reported the results of a pilot study of concurrent carboplatin (30 mg/m2 twice weekly) with radiation in 22 patients with stage IIA (>4 cm) to IIIB disease. The most significant chemotherapy-related side effects were grade 3 neutropenia and anemia. The authors reported 19 complete responders to this regimen, although only 11 patients were alive and disease-free at the time of their report. Because cisplatin... 

Verschraagen, M., Boven, E., Torun, E., Hausheer, F. H., Bast, A., and van der Vijgh, W. J. F., Possible (enzymatic) routes and biological sites for metabohc reduction of BNP7787, a new protector against cisplatin-induced side-effects. Biochemical Pharmacology 68(3), 493-502, 2004. 

Oxidative stress reduces the rate of cell proliferation, and that occurring during chemotherapy may interfere with the cytotoxic effects of antineoplastic drugs, which depend on rapid proliferation of cancer cells for optimal activity. Antioxidants detoxify ROS and may enhance the anticancer effects of chemotherapy. For some supplements, activities beyond their antioxidant properties, such as inhibition of topoisomerase II or protein tyrosine kinases, may also contribute. ROS cause or contribute to certain side effects that are common to many anticancer drugs, such as gastrointestinal toxicity and muagenesis. ROS also contribute to side effects that occur only with individual agents, such as doxorubicin-induced cardiotoxicity, cisplatin-induced nephrotoxicity, and bleomycin-induced pulmonary fibrosis. Antioxidants can reduce or prevent many of these side effects, and for some supplements the protective effect results from activities other than their antioxidant properties. Certain side effects, however, such as alopecia and myelosuppression, are not prevented... 

Two of the most important platinum anticancer drugs are cisplatin (2.13) and carboplatin (2.14). Cisplatin is effective against testicular tumours, ovarian carcinoma and some other types of cancer, but relatively inactive against breast and lung cancers it is also a very toxic compound. Side effects include loss of high-frequency hearing, neuropathy and nausea. Kidney damage may also result, but is minimised... 

Of the platinum-based drugs, cisplatin or cf -diarnmincdichloroplatinum (II) has been the most studied in treatments of cancerous tumours. Quantities of the drug administered in treatments must be carefully controlled because of appearances of side effects, primarily nephrotoxicity and nausea in patients. In some studies, ultrafilterable cisplatin, or free platinum in blood serum or plasma has been differentiated from platinum bound to proteins (Goel et al., 1990). HPLC has been used extensively in separations of intact cisplatin from other species. An anion-exchange column was connected to a post-column reactor and a UV-spectrophotometer for measurements of cisplatin concentrations in plasma and urine (Kizu et al., 1995). The detection limit was 20 nmol dm-3. Modes of action... 

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