Azacitidine to Restore Thyroid Function in Patients With Persistent or Metastatic Thyroid Cancer
Azacitidine to Restore Thyroid Function in Patients With Persistent or Metastatic Thyroid Cancer
RATIONALE: Azacitidine may help thyroid cancer cells regain the ability to take up iodine.
 This would allow the cancer to be detected and treated by radioactive iodine.

 PURPOSE: Phase I trial to study the effectiveness of azacitidine to restore thyroid function
 in treating patients who have persistent or metastatic thyroid cancer.
OBJECTIVES: I. Determine the ability of azacitidine to restore iodine uptake by
 dedifferentiated thyroid cancer, enabling detection and treatment with iodine I 131 in
 patients with metastatic follicular or papillary thyroid cancer. II. Evaluate different doses
 and schedules of azacitidine administration to determine an optimally effective combination
 for restoration of iodine I 131 uptake with acceptable toxicity in this patient population.
 III. Determine the efficacy of azacitidine plus iodine I 131 in this patient population.

 OUTLINE: This is a dose escalation study of azacitidine. Patients undergo a control phase
 consisting of oral liothyronine sodium twice daily on weeks 1-4 and a low iodine diet on
 weeks 4-7. At week 6, patients receive a scan dose of iodine I 131 followed by whole body
 scanning over 5 days. Beginning at week 7, patients undergo a treatment phase consisting of
 oral liothyronine sodium twice daily for 3 weeks, azacitidine subcutaneously daily for 10 or
 20 days (weeks 7-11) and a low iodine diet on weeks 8-11. During week 11, patients undergo
 additional whole body scanning over 5 days followed by a therapeutic dose of iodine I 131.
 Patients achieving successful therapy receive 5 additional doses of azacitidine. Cohorts of 4
 patients receive escalating doses of azacitidine until demonstrable radioiodine uptake is
 seen or the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
 preceding that at which 2 of 8 patients experience dose limiting toxicity. Patients are
 followed weekly for 8 weeks.

 PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study.
DISEASE CHARACTERISTICS: Radiologically confirmed persistent or metastatic follicular or
 papillary thyroid cancer following total thyroidectomy and radioiodine ablation therapy
 Metastatic disease confirmed histologically or cytologically or by elevated thyroglobulin
 levels No radioiodine uptake by whole body scanning Stable iodine contamination from
 radiologic contrast material within the past 10 months allowed, if absence of current
 contamination demonstrated by less than 80 micrograms of iodine in a 24 hour urine
 collection

 PATIENT CHARACTERISTICS: Age: Any age Performance status: Not specified Life expectancy:
 Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at
 least 100,000/mm3 Hepatic: SGOT/SGPT no greater than 2.5 times upper limit of normal (ULN)
 Bilirubin no greater than 1.5 times ULN Renal: Creatinine no greater than 1.5 times ULN OR
 Creatinine clearance at least 50 mL/min Other: Not pregnant or nursing Negative pregnancy
 test Fertile patients must use effective contraception

 PRIOR CONCURRENT THERAPY: At least 4 weeks since prior levothyroxine Any prior therapy for
 restoration of radioiodine uptake allowed, if unsuccessful and did not exceed treatment
 schedules planned for this study