A 58-Year-Old Man With Recurrent Head and Neck Cancer, Can Less Be More?
A Case of Recurrent Head and Neck Squamous Cell Carcinoma Treated With Ultra-Low-Dose Nivolumab
A 58-year-old man presented to the oncology clinic with progressive pain and swelling on the left side of his neck.
He had a history of carcinoma of the left buccal mucosa diagnosed 3 years earlier. At that time, he had undergone wide local excision with neck dissection followed by adjuvant radiotherapy.
He had remained disease-free for almost two years.
Six months earlier, he had developed a left cervical nodal recurrence. He received platinum-based chemotherapy with initial disease control, but the disease subsequently progressed.
At presentation, he complained of increasing neck pain, difficulty swallowing solid foods and a gradually enlarging cervical swelling.
Clinical Examination and PET-CT Findings
Clinical examination revealed a 5 × 4 cm fixed left cervical nodal mass with overlying skin infiltration.
PET-CT demonstrated:
- An intensely FDG-avid left cervical nodal mass
- Additional ipsilateral cervical lymphadenopathy
- Small pulmonary nodules suspicious for metastatic disease
- No other visceral metastases
A biopsy confirmed recurrent squamous cell carcinoma.
PD-L1 testing showed a CPS of 5.
His ECOG performance status was 1.
The disease was considered unresectable and the treatment intent was palliative.
Treatment Considerations
Standard-dose immune checkpoint inhibition was discussed with the patient.
However, the cost of conventional immunotherapy represented a major barrier.
The patient asked a simple question:
“Is there a way I can receive immunotherapy without spending that much?”
This raised an interesting therapeutic possibility.
Could a much smaller dose of nivolumab retain meaningful antitumour activity?
A Different Approach
After discussing the available evidence, treatment was initiated with triple metronomic chemotherapy combined with low dose nivolumab:
- Methotrexate 9 mg/m² orally once weekly
- Celecoxib 200 mg twice daily
- Erlotinib 150 mg once daily
- Nivolumab 40 mg intravenously every 3 weeks
The patient was closely monitored for toxicity, particularly mucositis, cytopenias, rash, diarrhea, thyroid dysfunction and other immune-related adverse events.
Clinical Response
After 3 months, there was a marked reduction in the cervical nodal mass.
The patient’s neck pain improved substantially and he was able to resume a normal diet.
A repeat PET-CT after six months demonstrated a sustained partial response with no new metastatic lesions.
Treatment was continued.
Why Is This Case Interesting?
At first glance, giving very low dose of nivolumab may appear almost counterintuitive.
The conventional nivolumab doses used in clinical practice are substantially higher. Yet pharmacologically, immune checkpoint blockade is different from conventional cytotoxic chemotherapy: the relationship between dose and biological activity is not necessarily linear.
The concept of low-dose immunotherapy is particularly relevant in countries where the cost of checkpoint inhibitors remains a major barrier to access.
Importantly, this is not simply an anecdotal concept.
A randomized phase III study conducted in India evaluated the addition of nivolumab 20 mg every 3 weeks to triple metronomic chemotherapy in advanced HNSCC. The addition of nivolumab improved median overall survival from 6.7 to 10.1 months and increased 1-year survival from 16.3% to 43.4%. (ASCO Publications)
More recent long-term follow-up presented in 2026 continued to demonstrate separation of the survival curves, with the benefit remaining evident at the four-year landmark. (ASCO Publications)
A prospective real-world study published in 2026 also reported encouraging outcomes with 20-mg nivolumab every three weeks combined with oral metronomic chemotherapy, although—as with any observational study—these results should be interpreted cautiously. (PubMed Central (PMC))
But Is 20 mg Really Equivalent to Standard-Dose Nivolumab?
That is the important caveat.
No.
The evidence supporting 20-mg nivolumab is specific to the treatment strategy studied—particularly its combination with metronomic chemotherapy—and should not automatically be extrapolated to every clinical situation in which nivolumab is used.
The evidence base for low-dose nivolumab is also considerably smaller than that for conventional-dose checkpoint inhibition.
Therefore, the concept should not be interpreted as:
“20 mg nivolumab is just as good as standard-dose nivolumab.”
Rather, the more appropriate interpretation is:
“In carefully selected patients, particularly where access to conventional immunotherapy is limited, ultra-low-dose nivolumab combined with metronomic chemotherapy represents a potentially effective and economically attractive treatment strategy.”
The Bigger Question
This case raises a broader issue that extends beyond head and neck cancer.
For expensive biological therapies, do we always need the maximum tolerated or conventionally approved dose to achieve meaningful biological activity?
Or could pharmacologically optimized lower doses provide:
- Similar biological efficacy
- Lower treatment costs
- Reduced drug wastage
- Greater access to therapy
- Potentially broader population-level benefit
The answer is unlikely to be the same for every immunotherapy or every tumour type.
But in recurrent head and neck cancer, the emerging evidence makes the question particularly compelling.
Sometimes, the most important innovation may not be discovering a new drug—but discovering how little of an existing drug is actually needed.
Clinical Note
Clinical note: This case is illustrative and not intended to represent a treatment recommendation for an individual patient. Low-dose nivolumab should be considered in the context of the available clinical evidence, regulatory status, institutional protocols, patient factors and informed consent.