Cisplatin
side effects, nutrient depletions, herbal interactions and health notes:
Data provided by Applied Health
• Cisplatin induces hypomagnesemia through its renal toxicity possibly by a direct injury to mechanisms of magnesium reabsorption in the ascending limb of the loop of Henle as well as the distal tubule. Consequently, cisplatin increases the urinary loss of magnesium. This drug-induced impairment of the renal tubules' ability to conserve magnesium may persist for months, or possibly years, after discontinuing use of the drug.1
• One British study found higher serum magnesium concentration levels that children given intravenous magnesium before and after administration of cisplatin than in those give magnesium only after the cisplatin. The researchers concluded that magnesium supplements should be given to patients receiving cisplatin during the precisplatin hydration period to prevent hypomagnesemia.2
• Individuals being treated with cisplatin often experience a decline in potassium levels that is unresponsive to potassium supplementation unless accompanied by supplemental magnesium. Magnesium is needed to maintain intracellular potassium.3
• nutrient adverse effects due to drug: It is important to avoid supplementation, especially of potassium, if kidney failure is present. Supplementation of magnesium and potassium can pose a significant risk for an individual on cisplatin due to the kidney damage which frequently results from the drug and impairs the urinary excretion of both minerals. Patients undergoing treatment with cisplatin need to have their doctor regularly monitor their kidney function along with magnesium and potassium status. Serum creatinine, BUN and creatinine clearance should be measured prior to initiating therapy and should be monitored throughout treatment. In this regard, many nutritionally-oriented practitioners find that a testing magnesium levels in red blood cells in far more reliable than testing serum magnesium. Only after such assessment should supplementation with magnesium or potassium be undertaken and then only under close supervision by the prescribing physician. Avoid supplementation, especially of Potassium, if kidney failure is present.4
• Recently, it has been reported that administration of sodium selenite reduces cisplatin toxicity without inhibiting the antitumor activity of cisplatin.5
• Cisplatin regimens can lead to a more or less pronounced hyponatremia in 4 to 10% of cases due to salt wasting with hypomagnesemia and normokalemia. Functional and renal failure and orthostatic hypotension can be observed6
• Cisplatin-induced hyponatremia requires specific management. Treatment is based on sodium intake which sometimes takes several months to replete stores.7
• Some human and animal studies have found that intravenous glutathione reduces the neurological toxicity of cisplatin and improves quality of life. More recently, Babu et al reported that administration of glutathione ester modulates the toxic side effect of cisplatin observed in kidney enzymes, and in blood parameters and concluded that glutathione ester plays an important role in protecting against the cisplatin induced nephrotoxicity by inhibiting the accumulation of platinum in kidneys. Even so, there is, as of yet, no conclusive evidence showing the effectiveness of oral glutathione.8
• Several studies indicate that quercetin exerts cisplatin sensitizing properties in cancer cells. Subsequently Kuhlmann et al conducted research to investigate whether quercitin could reduce cisplatin toxicity in cultured renal tubular cells. In their in vitro experiments they found that pretreatment of cells with quercetin for three hours significantly reduced the extent of cell damage due to cisplatin and that this protective activity was concentration dependent. They proposed that this activity most likely derived from quercetin's scavenging of free oxygen radicals. In contrast, they also noted that other bioflavonoids (catechin, silibinin, rutin) did not diminish cellular injury, even at higher concentrations. However, they also cautioned that, at least under these experimental circumstances, quercetin itself showed some intrinsic cytotoxicity at very high concentrations.9
• As with other antioxidants, individuals being treated with cisplatin should consult with their prescribing physician and/or a healthcare professional trained in nutritional therapies before initiating use of quercitin. Quercitin is commonly used at dosage levels of 400-500 mg, two to three times per day. Bioflavanoids such as quercitin are often taken with vitamin C, which it potentiates and protects.10
• Long-term kidney damage from cisplatin particularly affects the proximal tubular apparatus and can be detected by increased urinary excretion of brush-border enzymes and magnesium. Typical symptoms include decreases in creatinine clearance and increases in proteinuria, in the urinary activity of the proximal tubular enzymes L-alanine-aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase and in renal magnesium wasting.11
• Silymarin is an extract of milk thistle, and silibinin is a key component of this plant extract. In studies using rats Bokemeyer et al concluded that Silibinin protects against cisplatin-induced nephrotoxicity without compromising anti-tumor activity. They found that infusion of silibinin before cisplatin resulted in a significant decrease in glomerular (indicated by creatinine clearance and serum urea level) and tubular kidney toxicity (excretion of brush-border enzymes and magnesium). Likewise, Gaedeke et al found that the effects of cisplatin on creatinine clearance and proteinuria were totally prevented by a pretreatment of the animals with silibinin. Both studies reported that Silibinin given alone had no effect on renal function.12
• Individuals receiving cisplatin should consult with their prescribing physician and a healthcare professional trained in herbal medicine before introducing silymarin or derivative herbal products into their treatment regime.13
References1 Toffaletti J. Analyt Chem 1991 63(12):192R-194R; Lajer H, et al. Cancer Treat Rev. 1999 Feb;25(1):47-58; Koch Nogueira PC, et al. Pediatr Nephrol 1998 Sep;12(7):572-575
2 Kibirige MS, et al. Pediatr Hematol Oncol 1988;5(1):1-6
3 Rodriguez M, et al. Arch Intern Med 1989;149:2592-2594
4 Reference not Available
5 Olas B, Wachowicz B. Postepy Hig Med Dosw 1997;51(1):95-108
6 Peyrade F, et al. Presse Med 1997 Oct 25;26(32):1523-1525
7 Reference not Available
8 Jones MM, et al. Toxicology 1991;68(3):227-247; Cascinu S, et al. J Clin Oncol 1995;13:26-32; Smyth IF, et al. Ann Oncol 1997;8:569-573; Babu E, et al. Ren Fail 1999 Mar;21(2):209-217
9 Scambia G, et al. Anticancer Drugs. 1990 Oct;1(1):45-48; Cross HJ, et al. Int J Cancer. 1996 May 3;66(3):404-408; Kuhlmann MK, et al. Arch Toxicol 1998 Jul-Aug;72(8):536-540.
10 Reference not Available
11 Reference not Available
12 Bokemeyer C, et al. Br J Cancer 1996 Dec;74(12):2036-2041; Gaedeke J, et al. Nephrol Dial Transplant 1996 Jan;11(1):55-62.
13 Ariceta G, Rodriguez-Soriano J, Vallo A, Navajas A. Acute and chronic effects of cisplatin therapy on renal magnesium homeostasis. Med Pediatr Oncol 1997 Jan;28(1):35-40
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Disclaimers
The information in Drug Watch is provided as a courtesy to NewsTarget readers by Applied Health Solutions in cooperation with Healthway Solutions. Although the information is presented with scientific references, we do not wish to imply that this represents a comprehensive list of considerations about any specific drug, herb or nutrient. Nor should this information be considered a substitute for the advice of your doctor, pharmacist, or other healthcare practitioner. Please read the disclaimer about the intentions and limitations of the information provided on these pages. It is important to tell your doctor and pharmacist about all other drugs and nutritional supplements that you are taking if they are recommending a new medication. Copyright © 2007 by Applied Health Solutions, Inc. All rights reserved.
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