High Dose vs Low Dose I 131 +/- rhTSH for Differentiated Thyroid Cancer

RATIONALE: Radioactive iodine uses radiation to kill tumor cells. Giving iodine I 131 with or without thyroid-stimulating hormone after surgery may kill any tumor cells that remain after surgery. It is not yet known which dose of iodine I 131 is more effective when given with or without thyroid-stimulating hormone in treating thyroid cancer.

PURPOSE: This randomized phase III trial is studying two different doses of iodine I 131 to compare how well they work when given with or without thyroid-stimulating hormone in treating patients who have undergone surgery for thyroid cancer.

OBJECTIVES:

Primary

* Compare the percentage of successful remnant ablation at 6-8 months after administration of high- vs low-dose iodine I 131 with vs without recombinant thyroid-stimulating hormone in patients who have undergone total thyroidectomy for differentiated thyroid cancer.

Secondary

* Compare quality of life in patients treated with these regimens.
* Compare locoregional recurrence in patients treated with these regimens.
* Compare distant metastases, survival, and incidence of second primary malignancies in patients treated with these regimens.

OUTLINE: This is a multicenter, factorial, randomized study. Patients are stratified according to treatment center and disease stage (I vs II vs III vs IVA). Patients are randomized to 1 of 4 treatment arms.

Patients receive thyroid hormone replacement therapy (THRT)\* with thyroxine (T4)\*\* or liothyronine sodium (T3). Patients randomized to arm III or IV discontinue THRT 4 weeks (for patients receiving T4) or 2 weeks (for patients receiving T3) prior to remnant ablation.

NOTE: \*Some treatment centers may chose to avoid starting THRT in patients randomized to arm III or IV.

NOTE: \*\*Patients receiving T4 may be switched to T3 for 2 more weeks before discontinuing THRT.

* Arm I: Patients receive recombinant thyroid-stimulating hormone (rTSH) intramuscularly on days 1 and 2 and undergo remnant ablation with low-dose iodine I 131 on day 3.
* Arm II: Patients receive rTSH as in arm I and undergo remnant ablation with high-dose iodine I 131 on day 3.
* Arm III: Patients undergo remnant ablation with low-dose iodine I 131 as in arm I.
* Arm IV: Patients undergo remnant ablation with high-dose iodine I 131 as in arm II.

Quality of life is assessed at baseline, day 3 before remnant ablation, and at 3 months.

After completion of study therapy, patients are followed at 3 months, between 6-8 months, and then annually thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 468 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically confirmed differentiated thyroid cancer

  * T1-T3, Nx, N0, N1, M0 disease
* Has undergone one- or two-stage total thyroidectomy with or without lymph node dissection

  * All known tumor resected (R0)
* Requires radioiodine remnant ablation

  * Does not require mandatory recombinant thyroid-stimulating hormone
* No Hurthle cell carcinoma or aggressive variants, including any of the following:

  * Tall cell, insular, poorly differentiated disease with diffuse sclerosing
  * Anaplastic or medullary carcinoma

PATIENT CHARACTERISTICS:

* WHO performance status 0-2
* No severe comorbid conditions including, but not limited to, any of the following:

  * Unstable angina
  * Recent heart attack or stroke
  * Severe labile hypertension
  * Dementia
  * Concurrent dialysis
  * Tracheostomy needing care
  * Learning difficulties
  * Inability to comply with radiation protection issues
  * Requirement for frequent nursing or medical supervision that puts staff at risk for unacceptable radiation exposure
* No other cancers except basal cell skin cancer or carcinoma in situ of the cervix
* Not pregnant or nursing
* Negative pregnancy test
* Fertile female patients must use effective contraception during and for 6 months after radioiodine remnant ablation
* Fertile male patients must use effective contraception during and for 4 months after radioiodine remnant ablation

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* More than 3 months since prior contrast CT scan
* No prior iodine I 131 or iodine I 123 pre-ablation scan
* No prior treatment for thyroid cancer (except surgery)