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LETTER

Isotretinoin in Metastatic Thyroid Cancer

Anne R. Borner, MD; Dietmar Simon, MD; and Hans W. Muller-Gartner, MD

1 August 1997 | Volume 127 Issue 3 | Page 246

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TO THE EDITOR:

Although excellent results with 13-cis-retinoic acid (isotretinoin) have been reported in acute promyelocytic leukemia [1], the role of isotretinoin has not been fully established in the treatment of other malignancies. Oxyphilic follicular thyroid cancer is associated with a poor prognosis compared with other differentiated thyroid tumors [2]. No cure is known for metastatic disease. Spontaneous tumor regression in differentiated thyroid cancer is extremely rare. Influences on iodine metabolism, induction of 5' deiodinase, and decreased proliferation in follicular thyroid cancer cells have been observed [3-5].

In May 1993, a 72-year-old man presented with an oxyphilic follicular thyroid cancer with lymph node and pulmonary involvement. After thyroidectomy, neck dissection, ablative radioiodine therapy, and suppressive levothyroxine therapy, adjuvant therapy with isotretinoin (Accutane, Hoffmann-La Roche, Grenzach-Whylen, Switzerland), 60 mg/d, was started in July 1995 because of shortness of breath and exponentially increasing human thyroglobulin (hTg) levels. There were no severe side effects. The dyspnea disappeared 3 months after first administration. A cervical lymph node metastasis was removed in March 1996. Histologic examination showed a necrotic oxyphilic tumor with trabecular structure. The patient discontinued therapy with his medication twice, for 14 days in preparation for surgery and for 3 months starting in July 1996. While therapy was discontinued, hTg levels increased and dyspnea recurred. A least-squares model showed that hTg levels from July 1993 to May 1995 were different from those seen between July 1995 and May 1996, with a probability of more than 95% in a Mann-Whitney test (Figure 1 on page 246). Glucose hypermetabolism of the lung metastases assessed by F-18-FDG-PET (F-18-fluoro-deoxy-glucose available for position emission tomography) decreased (dose-uptake ratio, 6.1 ± 1.5 in October 1995 compared with 3.7 ± 1.3 in April 1996; P < 0.002). Computed tomography and chest radiography show unchanging diameters of the lung metastases. Isotretinoin therapy was started again in October 1996. As of February 1997, our patient is alive and well.

View larger version (23K): [in this window] [in a new window]   Figure 1. Follow-up from May 1993 to January 1997. Time course of tumor marker human thyroglobulin (hTg) and mean dose-uptake ratios (DUR) with SDs indicating glucose metabolism of the most prominent lung metastases are shown. The phases of isotretinoin therapy are marked.

 

This case report provides evidence that isotretinoin inhibits growth and induces regression of metastases in oxyphilic thyroid carcinoma.

Author and Article Information

Top Author & Article Info References

University Hospital Dusseldorf; Dusseldorf, Germany
Institute of Medicine Julich, Germany

References

Top Author & Article Info References

1. Degos L. Retinoic acid in promyelocytic leukemia. A model for differentiation therapy. Curr Opin Oncol. 1992; 4:42-52.

2. Muller-Gartner HW, Brzac HT, Rehpenning W. Prognostic indices for tumor relapse and tumor mortality in follicular thyroid carcinoma. Cancer. 1991; 67:1903-11.

3. Arai M, Tsushima T, Isozaki O, Shizume K, Emoto N, Demura H, et al. Effects of retinoids on iodine metabolism, thyroid peroxidase gene expression, and deoxyribonucleic acid synthesis in porcine thyroid cells in culture. Endocrinology. 1991; 129:2827-33.

4. Schreck R, Schnieders F, Schmutzler C, Koehrle J. Retinoids stimulate type I iodothyronine 5'deiodinase activity in human follicular thyroid carcinoma cell lines. J Clin Endocrinol Metab. 1994; 79:791-8.

5. Van Herle AJ, Agatep ML, Padua III DN, Totanes TL, Canlapan DV, Van Herle HM, et al. Effects of 13 cis-retinoic acid on growth and differentiation of human follicular carcinoma cells (UCLA RO 82 W-1) in vitro. J Clin Endocrinol Metab. 1990; 71:755-63.[Abstract]

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