Chemotherapy Regimens for Adenoid Cystic Carcinoma of the Head and Neck
For metastatic or locally recurrent adenoid cystic carcinoma (ACC) of the head and neck, cisplatin-vinorelbine combination provides the highest objective response rates among chemotherapy regimens, though overall response rates remain modest (typically <10%) and chemotherapy should be reserved primarily for symptomatic or rapidly progressive disease. 1
Key Distinction: ACC is NOT Squamous Cell Carcinoma
The provided guidelines focus predominantly on head and neck squamous cell carcinoma (HNSCC), which responds differently to chemotherapy than ACC. ACC is a rare salivary gland malignancy with distinct biology, characterized by indolent growth, perineural invasion, and limited chemosensitivity. 2, 3
Chemotherapy Regimens for ACC
Combination Chemotherapy (Preferred for Symptomatic Disease)
- Cisplatin-vinorelbine demonstrates the best objective response rates among combination regimens, though specific response percentages vary widely (0-70% across studies). 1
- This combination should be considered first-line for patients with symptomatic or rapidly progressive metastatic ACC. 1
Single-Agent Chemotherapy Options
- Cisplatin monotherapy has documented single-agent activity in ACC. 1
- Mitoxantrone shows objective responses in some patients. 1
- Vinorelbine as monotherapy demonstrates activity. 1
- Eribulin has shown objective responses. 1
- Epirubicin (30 mg/m² weekly for 8 weeks) produced 2 objective responses (10%) and disease stabilization in 50% of patients, with symptomatic improvement in 29.4% of cases occurring within 8 weeks. 4
Targeted Therapy Considerations
- EGFR inhibitors provide approximately 40% objective responses only when used in combination (not as monotherapy). 1
- VEGF inhibitors and histone deacetylase (HDAC) inhibitors achieve disease stabilization in progressive patients with approximately 10% objective response rates. 1
- c-KIT inhibitors as monotherapy yield objective response rates <5%. 1
- Direct PI3K/AKT/mTOR pathway inhibitors show 0% objective response rate. 1
Clinical Decision Algorithm
When to Use Chemotherapy in ACC
- Reserve chemotherapy for symptomatic disease or rapidly progressive metastatic/recurrent ACC not amenable to surgery or radiation. 4, 3
- Avoid chemotherapy in asymptomatic patients with indolent metastatic disease, as ACC can remain stable for prolonged periods without treatment. 3
Treatment Selection
- For symptomatic or rapidly progressive disease: Start with cisplatin-vinorelbine combination. 1
- For patients unable to tolerate combination therapy: Consider single-agent cisplatin, vinorelbine, or epirubicin. 1, 4
- For disease stabilization in progressive patients: Consider VEGF or HDAC inhibitors. 1
Role of Concurrent Chemoradiation
- For unresectable, node-negative, non-metastatic ACC: Definitive proton radiation therapy with concurrent cisplatin achieved complete response in 44% (4/9 patients) and disease stabilization in an additional 44%, though with significant toxicity including grade 3 acute toxicities and one grade 4 chronic optic nerve disorder. 5
- This approach should be considered for locally advanced unresectable disease where surgery is precluded by perineural or skull base invasion. 5
Critical Caveats
- Objective response rates to chemotherapy in ACC are predominantly <10%, far lower than in HNSCC where combination regimens achieve 20-40% response rates. 1, 6
- Symptomatic improvement may occur more frequently than objective radiographic responses, as demonstrated with epirubicin where 29.4% had symptomatic improvement despite only 10% objective response rate. 4
- Long-term survival is possible even with metastatic disease, so treatment decisions must balance potential toxicity against the indolent natural history in many patients. 2, 3
- Referral to specialized centers or tumor boards (such as REFCOR networks) is strongly recommended given the rarity of ACC and availability of clinical trials targeting specific molecular abnormalities. 1