Treatment of Advanced Medullary Thyroid Carcinoma with a Combination of Cyclophosphamide, Vincristine, and Dacarbazine: a Single-Center Experience

Abstract

Objective: Experience with chemotherapy in patients with medullary thyroid carcinomas (MTC) is limited. This retrospective study evaluated the outcome of a combination of cyclophosphamide, vincristine, and dacarbazine (‘CVD-regimen’), which has previously been suggested for treatment of malignant pheochromocytomas.

Methods: 9 patients (5 males; age 55.0±4.0 years) with MTC were enrolled. Prior to chemotherapy, progressive disease was established in all patients by use of WHO criteria. On day 1 of each cycle, patients started with cyclophosphamide 750 mg/m², vincristine 1.4 mg/m², and dacarbazine 600 mg/m²; on day 2, patients received dacarbazine alone (600 mg/m²). Treatment cycles were repeated at 21-day intervals and 6 cycles were planned for each patient. The standard imaging procedure was computed tomography, and the primary end point was the objective tumor response rate. After chemotherapy, patients were followed up until progression.

Results: 9 patients underwent a total of 57 cycles (mean 6.3±0.3 cycles). Treatment responses were: 0% complete response, 11% partial response, 56% stable disease, and 33% progressive disease. The median progression free survival was 13.6 months (range 5.8–24.2 months). The median change (baseline vs. end of treatment) of calcitonin was −19% (range −70% to +174%). Reversible myelosuppression and moderate gastrointestinal symptoms were the most common adverse events.

Conclusion: Although objective tumor res­ponse rates were low, the CVD regimen allowed disease stabilization for a substantial period of time and had acceptable toxicity. After initial surgery, chemotherapy may therefore be considered as a medical treatment option.

Key words

adverse events - efficacy - follow-up - outcome - progression - side effects - staging - toxicity - treatment

References

• 1 Ball DW. Medullary thyroid cancer: monitoring and therapy.  Endocrinol Metab Clin North Am. 2007;  36 823-837
• 2 Kloos RT, Eng C, Evans DB. et al . Medullary thyroid cancer: management guidelines of the American Thyroid Association.  Thyroid. 2008;  19 565-612
• 3 Roman S, Lin R, Sosa JA. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1 252 cases.  Cancer. 2006;  107 2134-2142
• 4 Miccoli P, Minuto MN, Ugolini C. et al . Clinically unpredictable prognostic factors in the outcome of medullary thyroid cancer.  Endocr Relat Cancer. 2007;  14 1099-1105
• 5 Wu LT, Averbuch SD, Ball DW. et al . Treatment of advanced medullary thyroid carcinoma with a combination of cyclophosphamide, vincristine, and dacarbazine.  Cancer. 1994;  73 432-436
• 6 Averbuch SD, Steakley CS, Young RC. et al . Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine.  Ann Intern Med. 1988;  109 267-273
• 7 Therasse P, Arbuck SG, Eisenhauer EA. et al . New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada.  J Natl Cancer Inst. 2000;  92 205-216
• 8 Kaplan EL, Meier P. Non-parametric estimation from incomplete observations.  J Am Stat Assoc. 1958;  53 457-481
• 9 Hartley A, Spooner D, Brunt AM. Management of malignant pheochromocytoma: a retrospective review of the use of MIBG and chemotherapy in the West Midlands.  Clin Oncol (R Coll Radiol). 2001;  13 361-366
• 10 Edström Elder E, Hjelm Skog AL, Hoog A. et al . The management of benign and malignant pheochromocytoma and abdominal paraganglioma.  Eur J Surg Oncol. 2003;  29 278-283
• 11 Robinson BG, Paz-Ares L, Krebs A. et al . Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.  J Clin Endocrinol Metab. 2010;  95 2664-2671
• 12 Wells Jr SA, Gosnell JE, Gagel RF. et al . Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer.  J Clin Oncol. 2010;  28 767-772

Correspondence