Successful dose escalation of lenvatinib for thyroid cancer after disease progression

Endocrine. 2022 Oct;78(1):77-84. doi: 10.1007/s12020-022-03117-5. Epub 2022 Jun 23.


Purpose: Lenvatinib is started at a standard dose, continuing with dose reduction and interruption, balancing between efficacy and adverse events (AEs). Because few drugs are available for thyroid cancer, efforts for continuing treatment with one agent, such as "dose escalation (DE)", are made. The dose is increased, aiming to regain the anti-tumor effect after dose reduction. The effects of lenvatinib DE in differentiated thyroid carcinoma (DTC) patients are reported.

Patients and methods: The efficacy of lenvatinib DE in DTC patients using the serum thyroglobulin (Tg) level and management of AEs was investigated.

Results: A total of 70 DE episodes in 33 patients were investigated. The median increased dose was 2.0 (1.0-14.0) mg, increased from 8.6 (2-16) mg to 10.1 (6-24) mg. The serum Tg level decreased in 53 DE episodes. Though the serum Tg level in 17 DE episodes was not decreased, the Tg rate of increase was decreased in 7 of these DE episodes using the Tg-doubling rate. Overall, clinical benefit was seen in 60 (86%) DE episodes. AEs that could not be controlled after DEs were seen in only 16% of cases. No intolerable AEs were observed in patients who received more drug holidays at the time of DEs compared to two times before the DEs.

Conclusion: DE may become one of the standard treatment strategies after disease progression if AEs are well managed. Drug holidays may be a key for successfully controlling AEs with DE. DE can be useful for controlling progressive disease with increasing Tg levels.

Keywords: Adverse events; Dose escalation; Dose intensity; Lenvatinib; Thyroglobulin-doubling rate; Thyroid carcinoma.

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Humans
  • Phenylurea Compounds* / administration & dosage
  • Phenylurea Compounds* / adverse effects
  • Quinolines* / administration & dosage
  • Quinolines* / adverse effects
  • Thyroid Neoplasms* / drug therapy
  • Thyroid Neoplasms* / pathology


  • Antineoplastic Agents
  • Phenylurea Compounds
  • Quinolines
  • lenvatinib