Combined all-trans retinoic acid with low-dose apatinib in treatment of recurrent/metastatic head and neck adenoid cystic carcinoma: A single-center, secondary analysis of a phase II study

Cancer Med. 2023 Apr;12(8):9144-9155. doi: 10.1002/cam4.5653. Epub 2023 Feb 3.


Background: Treatment options are limited for recurrent/metastatic adenoid cystic carcinoma of the head and neck (R/M ACCHN). We aimed to evaluate the preliminary results of the efficacy and safety of all-trans retinoic acid (ATRA) combined with low-dose apatinib in patients with R/M ACCHN according to a secondary analysis of a phase II study.

Methods: Patients from a phase II study (NCT02775370) who orally administered 500 milligram (mg) apatinib daily until treatment-related adverse events (AEs) intolerance or progression occurred were eligible for inclusion. Patients were further treated with combination therapy of ATRA (25 mg/m2 /day) and apatinib (250 mg/day) between March 2019 and October 2021 until progression of disease (PD).

Results: A total of 16 patients were included with nine (56.3%) males and aged 35-69 years old. All recruited patients previously received anti-angiogenic therapy then withdrew due to toxicities or progression occurred. The objective response rate (ORR) and disease control rate (DCR) were 18.8% and 100%, respectively. During a median follow-up of 23.9 months (range:17.8-31.7 months), 11 (68.8%) patients developed PD and one of them died in 20.9 months. The median of progression-free survival (PFS) was 16.3 months (95% CI: 7.2-25.4 months), and the 6-month, 12-month, and 24-month PFS rates were 100%, 81.3%, and 33.3%, respectively. The grade 3 adverse events were albuminuria (n = 2, 12.5%) and hand-foot syndrome (n = 1, 6.25%).

Conclusion: All-trans retinoic acid combined with low-dose apatinib might be a potential efficacy therapeutic option for patients with R/M ACCHN. This finding will be further confirmed by our registered ongoing trial, the APLUS study (NCT04433169).

Keywords: adenoid cystic carcinoma; all-trans retinoic acid; apatinib; head and neck cancer; oncological outcomes.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents* / adverse effects
  • Carcinoma* / drug therapy
  • Carcinoma, Adenoid Cystic* / drug therapy
  • Female
  • Head and Neck Neoplasms* / drug therapy
  • Humans
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Tretinoin / adverse effects


  • apatinib
  • Antineoplastic Agents
  • Tretinoin

Associated data