Journal of Bone and Mineral Metabolism

, Volume 24, Issue 3, pp 243–247 | Cite as

Tamoxifen flare hypercalcemia: an additional support for gallium nitrate usage

  • Govinda Pillai Arumugam
  • Sengoden Sundravel
  • Palanivel Shanthi
  • Panchanadham Sachdanandam
ORIGINAL ARTICLE

Abstract

In 12 of 93 hypercalcemic patients with metastatic advanced breast cancer treated with tamoxifen the most common life-threatening metabolic complication of flare hypercalcemia developed. All the hypercalcemic patients had osteolytic or mixed lytic and blastic bone metastases. In patients with advanced breast cancer, hypercalcemia develops within the first few weeks of initiation of tamoxifen therapy. In our study group, calcium levels were measured frequently in both serum and urine samples by a semi-autoanalyzer and an autoanalyzer, using standard methods. Elevation of calcium levels was noticed in the tamoxifen-receiving hypercalcemic breast cancer patients, and levels returned to normal when tamoxifen was withdrawn. The median duration of flare hypercalcemia was 9 days (range, 4–16 days). The median calcium value was 13.6 mg/dl (range, 11.7–15.8). The diagnosis of tamoxifen flare hypercalcemia was based on the normal pretreatment serum or urine calcium values and the occurrence of hypercalcemia within the first few weeks of tamoxifen initiation. There are no specific treatment recommendations for hormone flare hypercalcemia, except for tamoxifen withdrawal, which is usually temporary, and the introduction of a low dose of an antihypercalcemic drug. We evaluated the effect of such a drug, gallium nitrate, on flare hypercalcemia. All the patients were treated with hydration, and 6 patients, whose calcium level was above 13.6 mg/dl, were treated with a moderate dose of gallium nitrate (200 mg/m2 per kg) for 5 consecutive days, they achieved normocalcemia and continued with tamoxifen. The median time from hormonal drug initiation to flare hypercalcemia was 17.5 days, and median duration was 9 days. The above result indicates that the serious metabolic complication of hypercalcemia develops due to the iatrogenic effect of tamoxifen, but it can be controlled with an antihypercalcemic drug, gallium nitrate, while continuing tamoxifen therapy. It seems that the use of gallium nitrate in the treatment of flare hypercalcemia could allow safe readministration of tamoxifen and prevent premature tamoxifen discontinuance or withdrawal.

Key words

bone metastases breast cancer hypercalcemia gallium nitrate flare parathyroid hormone – related protein tamoxifen 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Legha, SS, Davis, HL, Muggia, FM 1978Hormonal therapy of breast cancer: new approaches and conceptsAnn Intern Med886977PubMedGoogle Scholar
  2. 2.
    Jolivet, J, Legault-Poisson, S, Band, P 1978Hormone therapy of breast cancer: tamoxifenUnion Med Can107964965PubMedGoogle Scholar
  3. 3.
    Plotkin, D, Lechner, JJ, Jung, WE, Rosen, PJ 1978Tamoxifen flare in advanced breast cancerJAMA826442646Google Scholar
  4. 4.
    Sztern, M, Barkan, A, Rakowsky, E, Shainkin-Kestenbaum, R, Marilus, R, Blum, I 1981Hypercalcemia in carcinoma of the breast without evidence of bone destruction: beneficial effect of hormonal therapyCancer123832385Google Scholar
  5. 5.
    Coleman, RE, Rubens, RD 1987The clinical course of bone metastases from breast cancerBr J Cancer556166PubMedGoogle Scholar
  6. 6.
    Kimmick, G, Muss, HB 1995Current status of endocrine therapy for metastatic breast cancerOncology (Huntingt)9877886889–890; discussion 892–894Google Scholar
  7. 7.
    Bernheim, JL, Callewaerts, W, Paridaens, R, Roobol, C 1983Human mammary tumor growth promotion by medroxyprogesterone acetate in the tumor stem cell clonogenic assayCancer Treat Rep67101102PubMedGoogle Scholar
  8. 8.
    Pritchard, KI, Clark, RM, Fine, S, Meakin, JW, Perrault, DJ, Sutherland, DJ 1978Tamoxifen and hypercalcemiaAnn Intern Med89423424PubMedGoogle Scholar
  9. 9.
    Davis, HL,Jr, Wiseley, AN, Ramirez, G, Ansfield, FJ 1973Hypercalcemia complicating breast cancer. Clinical features and managementOncology28126137PubMedGoogle Scholar
  10. 10.
    Legault-Poisson, S, Jolivet, J, Poisson, R, Beretta-Piccoli, M, Band, PR 1979Tamoxifen-induced tumor stimulation and withdrawal responseCancer Treat Rep6318391841PubMedGoogle Scholar
  11. 11.
    Veldhuis, JD, Santen, RJ 1979Tamoxifen flareJAMA825062507Google Scholar
  12. 12.
    Lerner, HJ, Band, PR, Israel, L, Leung, BS 1976Phase II study of tamoxifen: report of 74 patients with stage IV breast cancerCancer Treat Rep6014311435PubMedGoogle Scholar
  13. 13.
    Ralston, SH, Gallacher, SJ, Patel, U, Campbell, J, Boyle, IT 1990Cancer-associated hypercalcemia: morbidity and mortality. Clinical experience in 126 treated patientsAnn Intern Med1499504Google Scholar
  14. 14.
    Coleman, RE 1997Skeletal complications of malignancyCancer1515881594Google Scholar
  15. 15.
    Muggia, FM 1990Overview of cancer-related hypercalcemia: epidemiology and etiologySemin Oncol1739PubMedGoogle Scholar
  16. 16.
    Horwitz, KB, Koseki, Y, McGuire, WL 1978Estrogen control of progesterone receptor in human breast cancer: role of estradiol and antiestrogenEndocrinology10317421751PubMedGoogle Scholar
  17. 17.
    Tormey, DC, Simon, RM, Lippman, ME, Bull, JM, Myers, CE 1976Evaluation of tamoxifen dose in advanced breast cancer: a progress reportCancer Treat Rep Oct6014511459Google Scholar
  18. 18.
    Nikolic-Temasevic, Z, Jelic, S, Popov, I, Radosavljevic, D, Mitrovic, L 2001Tumor “flare” hypercalcemia – an additional indication for bisphosphonates?Oncology60123126Google Scholar
  19. 19.
    Legha SS, Powell K, Buzdar AU, Blumenschein GR (1981) Tamoxifen-induced hypercalcemia in breast cancer. 47:2803–2806Google Scholar
  20. 20.
    Burtis, WJ, Brady, TG, Orloff, JJ, Ersbak, JB, Warrell, RP,Jr, Olson, BR, Wu, TL, Mitnick, ME, Broadus, AE, Stewart, AF 1990Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancerN Engl J Med1911061112Google Scholar
  21. 21.
    Athanasou, NA, Wells, CA, Quinn, J, Ferguson, DP, Heryet, A, McGee, JO 1989The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biologyBr J Cancer59491498PubMedGoogle Scholar
  22. 22.
    Patterson, JS, Furr, BJ, Battersby, LA 1978Tamoxifen and hypercalcemiaAnn Intern Med891013PubMedGoogle Scholar
  23. 23.
    Bernstein, LR 1998Related articles, links mechanisms of therapeutic activity for galliumPharmacol Rev50665682PubMedGoogle Scholar
  24. 24.
    Collery, P, Keppler, B, Madoulet, C, Desoize, B 2002Gallium in cancer treatmentCrit Rev Oncol Hematol42283296PubMedGoogle Scholar
  25. 25.
    Warrell, RP,Jr, Bosco, B, Weinerman, S, Levine, B, Lane, J, Bockman, RS 1990Gallium nitrate for advanced Paget disease of bone: effectiveness and dose-response analysisAnn Intern Med113847851PubMedGoogle Scholar
  26. 26.
    Niesvizky, R, Choy, CG, Siegel, D 2002Extended survival in advanced-stage multiple myeloma patients treated with gallium nitrateLeuk Lymphoma43603605Google Scholar
  27. 27.
    Berheault-Cvitkovic F, Armand J-P, Tubuana-Hulin M (1996) Randomized, double blind comparison of pamidronate vs gallium nitrate for acute control of cancer-related hypercalcemia. Presented at the 9 EORTC/NC1 symposium, Amsterdam, March 1996Google Scholar

Copyright information

© Springer-Verlag Tokyo 2006

Authors and Affiliations

  • Govinda Pillai Arumugam
    • 1
  • Sengoden Sundravel
    • 1
  • Palanivel Shanthi
    • 2
  • Panchanadham Sachdanandam
    • 1
  1. 1.Department of Medical Biochemistry, Dr.A.L.M. Post-Graduate Institute of Basic Medical SciencesUniversity of Madras, Taramani CampusChennaiIndia
  2. 2.Department of Pathology, A.L.M. Post – Graduate Institute of Basic Medical SciencesUniversity of Madras, Taramani CampusChennaiIndia

Personalised recommendations