Zoledronic Acid, Hypocalcemia and Renal Dysfunction in Thalidomide-Treated Myeloma Patients

Reviewer: Walter Sall, MD
Last Modified: December 10, 2002

Presenter: Bethan Myers
Presenter's Affiliation: Queen's Medical Centre, University Hospital, Nottingham
Type of Session: Scientific


  • Zoledronic acid (Zometa) is a new bisphosphonate hundreds to thousands of times more potent than it's predescessors.
  • ASCO 2002 guidelines recommend the use of bisphoshonates to prevent progression of lytic bone lesions in multiple myeloma.
  • Zometa has become increasingly popular in this setting because of its potency, cost eqivalence and short infusion time.
  • Prior studies have shown eqivalent rates of renal impairment with Zometa or Pamidronate. This study describes a patient cohort treated concurrently with Zometa and thalidomide having a much higher than expected rate of renal toxicity.

Materials and Methods

  • 16 patients with advanced Multiple Myeloma and osteolyitc lesions were switched from pamidronate to Zometa in 2001. All had received pamidronate for at least one year with stable disease and stable renal function.
  • 11 patients were concurrently receiving Thalidomide, 5 were receiving melphalan/prednisolone and 2 were receiving no other therapy. Mean age was 76.5
  • 3 doses of Zometa, 4mg iv, were given 4 weeks apart.


  • Mean pretreatment creatinine was 93 mmol/L
  • Two patients had a dramatic creatinine rise after the third dose (331 and 517 mmol/L) with symptomatic hypocalcemia. One patient had a creatinine rise to 239 mmol/L but no associated hypocalcemia.
  • These three patients had all been receiving thalidomide (100-200mg) and had responsive disease.
  • Notably, all of these patients had stable paraprotein levels and no albuminuria prior to enrollment greatly diminishing the liklihood that their renal dysfunction resulted from myeloma progression.

Author's Conclusions

  • Though there are no published data to this effect, it appears that there may be a drug interaction between thalidomide and Zometa in certain myeloma patients.
  • Risk of Grade III/IV renal toxicity in this study is 12.5%, much greater than the 1% risk found in Berenson's study of Zometa.
  • Further study is indicated to determine if myeloma patients with impaired renal function need modified Zometa dosing, especially those on concurrent thalidomide.

Clinical/Scientific Implications

    The high incidence of renal toxicity in myeloma patients treated with concurrent thalidomide and Zometa in this study is certainly concerning. Unfortunately, the patient numbers are too low to establish causality or make treatment recommendations in this group. Further investigation of patients previously treated with this combincation of medications is indicated to discover if a drug interaction truly exists. Until then, thalidomide and Zometa should be used very cautiously in conjunction with one another.

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