FDA-Approved Chemotherapy for Adenoid Cystic Carcinoma of the Head and Neck
There is no FDA-approved chemotherapy regimen specifically for adenoid cystic carcinoma (ACC) of the head and neck, and no standard chemotherapy can be recommended based on current evidence. 1, 2
Key Clinical Reality
- ACC is fundamentally different from squamous cell carcinoma of the head and neck—it is a rare salivary gland malignancy that does not respond to standard head and neck cancer chemotherapy protocols 2, 3
- The NCCN guidelines for head and neck cancers 4 specifically address squamous cell carcinomas and do not provide recommendations for ACC
- Objective response rates to chemotherapy in ACC are predominantly less than 10% (range 0-70%), making chemotherapy largely ineffective 1
Treatment Approach for Advanced/Metastatic ACC
Primary treatment remains surgical resection with postoperative radiotherapy (preferably intensity-modulated radiotherapy or hadron therapy in specific situations). 2
When Systemic Therapy is Considered
For unresectable recurrent or metastatic disease, the following have shown limited activity:
Chemotherapy options with documented responses (though not FDA-approved for ACC):
- Cisplatin-vinorelbine combination achieved the best objective response rates among chemotherapy regimens 1
- Single-agent responses documented with cisplatin, mitoxantrone, vinorelbine, and eribulin 1
- Cyclophosphamide, pirarubicin, and cisplatin (CAP therapy) showed 36% response rate in a small series (n=14) with median response duration of 16 months 5
Targeted therapy considerations:
- EGFR inhibitors provided 40% objective responses only in combination regimens 1
- VEGF and histone deacetylase inhibitors achieved disease stabilization in progressive patients with approximately 10% objective response 1
- c-KIT inhibitors yielded less than 5% objective response rates 1
- PI3K/AKT/mTOR pathway inhibitors showed 0% objective response rate 1
Critical Management Principles
- Referral to specialized centers is essential—patients should be discussed in multidisciplinary consultation meetings such as the French network of experts in rare head and neck tumors (REFCOR) or Molecular Tumor Boards to access clinical trials 1
- ACC is characterized by TP53 wild-type status in over 95% of cases, making it biologically distinct from squamous cell carcinoma 6
- Identified molecular abnormalities (MYB-NFIB fusion, Notch 1 mutations) may provide future therapeutic opportunities but currently lack approved targeted agents 2
Important Caveats
- Do not extrapolate standard head and neck squamous cell carcinoma regimens (cisplatin-based chemoradiation, platinum/5-FU/cetuximab) to ACC—these are not effective and lack evidence 1, 2, 3
- ACC demonstrates an indolent course with late recurrences and lung metastases, but long-term survival is possible even with metastatic disease 2, 3
- Clinical trial enrollment should be prioritized given the lack of effective standard systemic therapy 1, 2