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