Abstract
Skeletal metastases from thyroid cancer are poorly responsive to medical or radioiodine treatment. Bone destruction in skeletal metastases results from osteoclast-induced bone resorption. Therefore, a new approach in the therapy of bone metastases consists in using aminobisphosphonates, such as pamidronate, which are potent inhibitors of osteoclastic activity. In the present study, 10 thyroid cancer patients with painful osteolytic bone metastases were administered pamidronate (90 mg, as a 2 hour intravenous infusion) monthly for 12 consecutive cycles. Bone pain, quality of life, performance status, analgesic consumption and disease staging were evaluated before and during the trial. The patients who had been administered pamidronate showed a significant decrease in bone pain (P = 0.0052). Performance status improved nearly significantly (P = 0.051), while the quality of life showed a remarkable amelioration. However, no significant decrease in analgesic consumption was recorded. Partial radiographic response of bone lesions was observed in 2/10 patients. The side effects of pamidronate were mild and transient. In conclusion, monthly infusion of pamidronate is a well-tolerated treatment that induces significant relief from bone pain and improves the quality of life of thyroid cancer patients with symptomatic and osteolytic bone metastases. © 2001 Cancer Research Campaign http://www.bjcancer.com
Keywords: pamidronate, thyroid cancer, bone metastases
Full Text
The Full Text of this article is available as a PDF (59.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aparicio A., Gardner A., Tu Y., Savage A., Berenson J., Lichtenstein A. In vitro cytoreductive effects on multiple myeloma cells induced by bisphosphonates. Leukemia. 1998 Feb;12(2):220–229. doi: 10.1038/sj.leu.2400892. [DOI] [PubMed] [Google Scholar]
- Benford H. L., Frith J. C., Auriola S., Mönkkönen J., Rogers M. J. Farnesol and geranylgeraniol prevent activation of caspases by aminobisphosphonates: biochemical evidence for two distinct pharmacological classes of bisphosphonate drugs. Mol Pharmacol. 1999 Jul;56(1):131–140. doi: 10.1124/mol.56.1.131. [DOI] [PubMed] [Google Scholar]
- Body J. J. Metastatic bone disease: clinical and therapeutic aspects. Bone. 1992;13 (Suppl 1):S57–S62. doi: 10.1016/s8756-3282(09)80011-2. [DOI] [PubMed] [Google Scholar]
- Cascinu S., Graziano F., Alessandroni P., Ligi M., Del Ferro E., Rossi D., Ficarelli R., Catalano G. Different doses of pamidronate in patients with painful osteolytic bone metastases. Support Care Cancer. 1998 Mar;6(2):139–143. doi: 10.1007/s005200050148. [DOI] [PubMed] [Google Scholar]
- Cella D. F., Tulsky D. S., Gray G., Sarafian B., Linn E., Bonomi A., Silberman M., Yellen S. B., Winicour P., Brannon J. The Functional Assessment of Cancer Therapy scale: development and validation of the general measure. J Clin Oncol. 1993 Mar;11(3):570–579. doi: 10.1200/JCO.1993.11.3.570. [DOI] [PubMed] [Google Scholar]
- Coleman R. E., Rubens R. D. Bone metastases and breast cancer. Cancer Treat Rev. 1985 Dec;12(4):251–270. doi: 10.1016/0305-7372(85)90008-8. [DOI] [PubMed] [Google Scholar]
- Coleman R. E., Woll P. J., Miles M., Scrivener W., Rubens R. D. Treatment of bone metastases from breast cancer with (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD). Br J Cancer. 1988 Nov;58(5):621–625. doi: 10.1038/bjc.1988.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Derenne S., Amiot M., Barillé S., Collette M., Robillard N., Berthaud P., Harousseau J. L., Bataille R. Zoledronate is a potent inhibitor of myeloma cell growth and secretion of IL-6 and MMP-1 by the tumoral environment. J Bone Miner Res. 1999 Dec;14(12):2048–2056. doi: 10.1359/jbmr.1999.14.12.2048. [DOI] [PubMed] [Google Scholar]
- Gillenwater A. M., Weber R. S. Thyroid carcinoma. Cancer Treat Res. 1997;90:149–169. doi: 10.1007/978-1-4615-6165-1_8. [DOI] [PubMed] [Google Scholar]
- Grebe S. K., Hay I. D. Follicular thyroid cancer. Endocrinol Metab Clin North Am. 1995 Dec;24(4):761–801. [PubMed] [Google Scholar]
- Hayward J. L., Carbone P. P., Heuson J. C., Kumaoka S., Segaloff A., Rubens R. D. Assessment of response to therapy in advanced breast cancer: a project of the Programme on Clinical Oncology of the International Union Against Cancer, Geneva, Switzerland. Cancer. 1977 Mar;39(3):1289–1294. doi: 10.1002/1097-0142(197703)39:3<1289::aid-cncr2820390340>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
- Lipton A., Glover D., Harvey H., Grabelsky S., Zelenakas K., Macerata R., Seaman J. Pamidronate in the treatment of bone metastases: results of 2 dose-ranging trials in patients with breast or prostate cancer. Ann Oncol. 1994;5 (Suppl 7):S31–S35. [PubMed] [Google Scholar]
- Lupoli G., Cascone E., Arlotta F., Vitale G., Celentano L., Salvatore M., Lombardi G. Treatment of advanced medullary thyroid carcinoma with a combination of recombinant interferon alpha-2b and octreotide. Cancer. 1996 Sep 1;78(5):1114–1118. doi: 10.1002/(SICI)1097-0142(19960901)78:5<1114::AID-CNCR23>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
- Marcocci C., Pacini F., Elisei R., Schipani E., Ceccarelli C., Miccoli P., Arganini M., Pinchera A. Clinical and biologic behavior of bone metastases from differentiated thyroid carcinoma. Surgery. 1989 Dec;106(6):960–966. [PubMed] [Google Scholar]
- Maxon H. R., 3rd, Smith H. S. Radioiodine-131 in the diagnosis and treatment of metastatic well differentiated thyroid cancer. Endocrinol Metab Clin North Am. 1990 Sep;19(3):685–718. [PubMed] [Google Scholar]
- Miller A. B., Hoogstraten B., Staquet M., Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207–214. doi: 10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
- Morton A. R., Cantrill J. A., Pillai G. V., McMahon A., Anderson D. C., Howell A. Sclerosis of lytic bone metastases after disodium aminohydroxypropylidene bisphosphonate (APD) in patients with breast carcinoma. BMJ. 1988 Sep 24;297(6651):772–773. doi: 10.1136/bmj.297.6651.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Proye C. A., Dromer D. H., Carnaille B. M., Gontier A. J., Goropoulos A., Carpentier P., Lefebvre J., Decoulx M., Wemeau J. L., Fossati P. Is it still worthwhile to treat bone metastases from differentiated thyroid carcinoma with radioactive iodine? World J Surg. 1992 Jul-Aug;16(4):640–646. doi: 10.1007/BF02067343. [DOI] [PubMed] [Google Scholar]
- Reszka A. A., Halasy-Nagy J. M., Masarachia P. J., Rodan G. A. Bisphosphonates act directly on the osteoclast to induce caspase cleavage of mst1 kinase during apoptosis. A link between inhibition of the mevalonate pathway and regulation of an apoptosis-promoting kinase. J Biol Chem. 1999 Dec 3;274(49):34967–34973. doi: 10.1074/jbc.274.49.34967. [DOI] [PubMed] [Google Scholar]
- Schlumberger M. J. Papillary and follicular thyroid carcinoma. N Engl J Med. 1998 Jan 29;338(5):297–306. doi: 10.1056/NEJM199801293380506. [DOI] [PubMed] [Google Scholar]
- Shipman C. M., Rogers M. J., Apperley J. F., Russell R. G., Croucher P. I. Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity. Br J Haematol. 1997 Sep;98(3):665–672. doi: 10.1046/j.1365-2141.1997.2713086.x. [DOI] [PubMed] [Google Scholar]
- Tong D., Gillick L., Hendrickson F. R. The palliation of symptomatic osseous metastases: final results of the Study by the Radiation Therapy Oncology Group. Cancer. 1982 Sep 1;50(5):893–899. doi: 10.1002/1097-0142(19820901)50:5<893::aid-cncr2820500515>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
- Tubiana M., Haddad E., Schlumberger M., Hill C., Rougier P., Sarrazin D. External radiotherapy in thyroid cancers. Cancer. 1985 May 1;55(9 Suppl):2062–2071. doi: 10.1002/1097-0142(19850501)55:9+<2062::aid-cncr2820551406>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
- Vitale G., Tagliaferri P., Caraglia M., Rampone E., Ciccarelli A., Bianco A. R., Abbruzzese A., Lupoli G. Slow release lanreotide in combination with interferon-alpha2b in the treatment of symptomatic advanced medullary thyroid carcinoma. J Clin Endocrinol Metab. 2000 Mar;85(3):983–988. doi: 10.1210/jcem.85.3.6435. [DOI] [PubMed] [Google Scholar]
- van Beek E., Pieterman E., Cohen L., Löwik C., Papapoulos S. Nitrogen-containing bisphosphonates inhibit isopentenyl pyrophosphate isomerase/farnesyl pyrophosphate synthase activity with relative potencies corresponding to their antiresorptive potencies in vitro and in vivo. Biochem Biophys Res Commun. 1999 Feb 16;255(2):491–494. doi: 10.1006/bbrc.1999.0224. [DOI] [PubMed] [Google Scholar]