Table 3.
Update of clinical trials of redifferentiation strategy for radioactive-iodine (RAI) refractory differentiated thyroid cancers
| Classification | Drug | Type of study | Patients (n) | Dose | Duration of treatment before RAI | Main Result | Reference |
|---|---|---|---|---|---|---|---|
| BRAF inhibitor | Dabrafenib | Interventional study | 10 | 150 mg | 25 days | Increase of RAI uptake (6/10); PR (2/6) and SD (4/6) after RAI therapy |
250 |
| Vemurafenib | Pilot study | Total 12 10 evaluable |
960 mg | 4 weeks | Increase of RAI uptake (4/10); Tumor regression after RAI therapy (3/4) |
251 | |
| HDAC inhibitor | Romidepsin (Depsipeptide) |
Phase I | 11 | 1 to 9 mg/m2 | 6-112 weeks (21 days cycle) |
Faintly increase of RAI uptake (2/6) | 247 |
| Phase II | 20 | 13 mg/m2 | 0.46-12 months (28 days cycle) |
Increase of RAI uptake (2/16) | 248 | ||
| Valproic acid | Phase II | 13 | 500 mg once for 3 days followed by 500 mg | 10 weeks | Increase of RAI uptake (0/10) | 249 | |
| Vorinostat | Phase I | 6 | 200-400 mg | 12-37+ months (4 weeks cycle) |
Increase of RAI uptake (1/3) | 246 | |
| - | Lithium | Pilot study | 12 | 1200 mg | Unknown duration (During and after 2nd RAI therapy) |
Increase of RAI uptake (5/12); *Mixed pattern of RAI uptake (2/12); Response for RAI therapy (0/12). |
254 |
| MEK inhibitor | Selumetinib | Pilot study | Total 24 20 evaluable |
75 mg | 4 weeks | Increase of RAI uptake (12/20); Reached dosimetry threshold for RAI therapy (8/12); PR (5/8) and SD (3/8) after RAI therapy. |
7 |
| Non-nucleoside reverse transcriptase inhibitor | Nevirapine | Case report | 1 | 200 mg | Unknown duration | Increase of RAI uptake in metastatic sites | 253 |
| PPARɣ agonist | Pioglitazone | Case report | 5 | 30 mg followed by 45 mg | 6 months (30 mg dose for 2 weeks followed by 45 mg dose) | Increase of RAI uptake (0/5) | 245 |
| Rosiglitazone | Case report | 1 | 8 mg | 3 months | Increase of RAI uptake | 239 | |
| Case report | 1 | 8 mg | 2 months | Increase of RAI uptake; Tumor regression after RAI therapy. |
240 | ||
| Phase II | 10 | 4 mg or 8 mg | 1 week for 4 mg dose; 7 weeks for 8 mg dose | Increase of RAI uptake (4/10) | 241 | ||
| Phase II | 20 | 4 mg or 8 mg | 1 week for 4 mg dose; 7 weeks for 8 mg dose |
PR for RAI uptake and Tg level (5/20) | 242 | ||
| PPARɣ agonist | Rosiglitazone | Pilot study | 5 | 4 mg or 8 mg | 1 month for 4 mg dose; 2 months for 8 mg dose |
Faintly increase of RAI uptake (1/5) | 238 |
| Pilot study | 23 | 8 mg | 6 weeks | Increase of RAI uptake (5/23) | 243 | ||
| Pilot study | 9 | 4 mg followed by 8 mg | 6 months (4 mg dose for 2 weeks followed by 8 mg dose) | Increase of RAI uptake (5/9); Tumor regression after RAI therapy (3/9) |
244 | ||
| Retinoic acids | Bexarotene | Pilot study | 12 | 300 mg | 6 weeks | PR for RAI uptake (8/11) | 234 |
| Isotretinoin | Pilot study | 10 | 1.5 mg/kg | 6 weeks | Increase of RAI uptake (4/10) | 225 | |
| Pilot study | 50 | 1.5 mg/kg | 5 weeks | Increase of RAI uptake (21/50); Tumor regression after RAI therapy (6/37) |
226 | ||
| Pilot study | 25 | 1 mg/kg | 3 months | Increase of RAI uptake (5/25) | 227 | ||
| Pilot study | 5 | 1.0 to 1.5 mg/kg | 5 weeks | Increase of RAI uptake (3/5); Decrease of tumor size (1/5) |
228 | ||
| Pilot study | 11 | 1.5 mg/kg | 8 weeks | Increase of RAI uptake (2/11) | 229 | ||
| Pilot study | 27 | 0.66-1.5 mg/kg | 5-12 weeks | Optimal positive RAI uptake (9/27); Suboptimal RAI uptake (10/27); Tumor regression or stabilization after RAI therapy (7/17) |
230 | ||
| Pilot study | 47 | 1-1.5 mg/kg | 6 weeks | CR for RAI uptake (1/47); PR for RAI uptake (9/47) |
231 | ||
| Phase II | 53 | 1.0 mg/kg/day for 1 week followed by 1.5 mg/kg | 6 weeks | Increase of RAI uptake (9/53) | 232 | ||
| Phase II | 16 | 1.5 mg/kg | 8 weeks | Increase of RAI uptake (1/16) | 233 | ||
| Tretinoin | Pilot study | 13 | 1.5 mg/kg | 1.5-18 months | Faintly increase of RAI uptake (6/13); PR for RAI therapy (1/13) |
236 | |
| Retrospective study | 11 | 1.00±0.09 mg·kg-1·d-1 | 30 or 60 days | Re-induction of RAI uptake (4/11); PR for RAI therapy (5/11) |
235 | ||
| Combination | Dabrafenib ± Trametinib, Vemurafenib, Trametinib, Investigational MEK inhibitor |
Retrospective study | 13 | Unknown | Median duration of treatment: 14.3 months (range, 0.9 to 76.4) | Increase of RAI uptake (9/13); PR (3/9) and SD (6/9) after RAI therapy |
252 |
| Trametinib ± Dabrafenib, Vemurafenib + Cobimetinib |
Retrospective, cohort study | 6 | Unknown | 4 weeks | Increase of RAI uptake (4/6); PR (3/4) and SD (1/4) after RAI therapy |
10 |
Abbreviations: CR: complete response; HDAC: histone deacetylase; N/A: not available; PPARɣ: peroxisome proliferator-activated receptor; PR: partial response; RAI: radioactive iodine; SD: stable disease. *Mixed pattern means 2 regions of interest with different effects of lithium.