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Avoiding Nephrotoxicity from Chemo


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									Nephrotoxicity_1209.qxp    11/24/09   12:14 PM     Page 1

      www.renalandurologynews.com                                                                                    DECEMBER 2009          Renal & Urology News 11

       Avoiding Nephrotoxicity from Chemo
      Nephrologist offers advice related to the use of cisplatin, gemcitabine, and other agents
      BY ROSEMARY FREI, MSc                      toxicity, including exploring drugs                                                   of thrombotic microangiopathy, acute
      TORONTO — Clinicians can take              that inhibit uptake of cisplatin by                                                   kidney injury (AKI), and chronic
      steps to prevent nephrotoxicity from       the renal tubules or that stop the                                                    kidney disease.
      chemotherapy agents, according to          apoptotic effect of cisplatin on                                                        “When this drug started to be used
      a researcher who spoke here at             these cells.                                                                          at the Princess Margaret Hospital [in
      the Prevention in Renal Disease 8th          “All of these studies show some                                                     Toronto], where I practice, all of
      Annual Conference.                         reduction of nephrotoxicity, but no                                                   my colleagues were seeing a lot of
        Cisplatin is among the drugs dis-        single agent or combination of agents                                                 patients with quite severe hyperten-
      cussed by Robert Richardson, MD,           has been able to entirely reduce                                                      sion, many with significant protein-
      Professor of Nephrology at the             nephrotoxicity,” he said. “I wouldn’t                                                 uria and in some cases nephrotic
      University of Toronto. The medica-         be surprised, though, if in the next                                                  proteinuria among those receiving
      tion, which is effective for a wide        few years there are agents or combi-                                                  bevacizumab,” he related. “But I have
      variety of solid tumors, frequently        nations of agents that may selectively                                                the impression that we’re not seeing
      results in nephrotoxicity.                 eliminate nephrotoxicity.”                                                            as many of these side effects now that

        “About a third of patients in all          Even when a therapeutic bullet is                                                   the drug is better understood.”
      studies involving cisplatin develop        found that stops nephrotoxicity, there                                                  In addition, Dr. Richardson in-
      nephrotoxicity, mainly manifested by       will always be residual concerns about                                                formed listeners that ifosfamide pro-
      an elevated serum creatinine,” he said.    concomitant reduction of the effec-                                                   duces subtle tubular dysfunction in
      “This typically occurs about 10 days       tiveness of cisplatin, Dr. Richardson      agent is not that of an endothelial        up to 90% of patients, but it is usual-
      after administration of the drug. It is    noted. Hence, researchers will have        antagonist.” The effects are usually       ly reversible and can be prevented
      also usually non-oliguric, so the pa-      to produce data showing the anti-          reversible when the medication is          altogether by limiting the drug’s dose
      tient is unaware of this.”                 nephrotoxicity agents do not affect        stopped, he said. Clinicians should        to less than 84 g/m2. Moreover, he
        The most effective ways to address       the tumor-remission rates with cis-        assess patients after each course of       said AKI from high-dose methotrex-
      this nephrotoxicity include reducing       platin before clinicians or regulators     gemcitabine for any signs of nephro-       ate affects about 2% of patients.
      the cisplatin dose or switching to         will take notice, he said.                 toxicity such as a decrease in hemo-       Dr. Richardson recommends prevent-
      the cisplatin analogue carboplatin,          Dr. Richardson also discussed gem-       globin, platelets or glomerular filtra-    ing it by using alkaline diuresis begin-
      Dr. Richardson said. Saline volume         citabine, which he said is not directly    tion rate, and for an increase in BP or    ning 12 hours before the first infusion
      expansion during drug administration       nephrotoxic but causes thrombotic          the occurrence of dyspnea or central       and continuing for 12 hours after the
      is an alternate strategy; it reduces       microangiopathy in up to 1.4% of           nervous system changes.                    infusion. For patients who develop
      nephrotoxicity in about one-third of       patients with solid tumors. “It’s a sort     Dr. Richardson also observed that        AKI after high-dose methotrexate
      individuals, Dr. Richardson note
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