Vivek N. Patel, MD
E. Ronald Hale, MD, MPH
Why is this article contemporary?
Despite great strides forward in the organ preservation treatment of head and neck cancer, recurrent disease in the inoperable patient afflicted with squamous cell carcinoma of the head and neck (SCCHN) often remains challenging. Re-excision is usually limited by radiation effect of prior treatment, or a history of a prior resection. For these patients, systemic therapy, re-irradiation, and other supportive care are often the only available options.
Systemic therapy alone is typically considered the standard palliative treatment option for recurrent SCCHN patients. Re-irradiation of the head and neck can be fraught with hazards due to normal tissue tolerance saturation from prior radiation treatments. Little available normal tissue tolerance will often result in a sub-optimal treatment plan. Older palliative radiation regimens such as ”quad-shot“ therapy require considerable expertise in treating these types of patients in order to be administered safely.
This interesting single institutional study by Patel et al is contemporary as it addresses the use of low-dose fractionated radiation therapy (LDFRT) in addition to cetuximab and docetaxel in patients in this unique situation. The investigators used a regimen as follows: cetuximab 400mg/m2 was given as loading dose only on day 1 of week 1 and then, subsequently, in 250 mg/m2
weekly doses on day 1 of each following week (weeks 2 to 7). Docetaxel 20 mg/ m2
was administered weekly on day 1 from week 2 to 7. Radiotherapy consisted of 0.5 Gy/fraction twice a day at least 6 hours apart on days 2 and 3 of weeks 2 to 7 for a total dose of 12 Gy. Patel at al suggest that this regimen is well-tolerated, however the benefit may be marginal.
For this appropriate subset of patients, LDFRT and chemotherapy may offer transient palliation accompanied by low treatment related morbidity.
In this phase II study, cetuximab 400 mg/m2 was given in the usual loading dose only on day 1 of week 1 and then, subsequently, in 250mg/m2 weekly doses on day 1 of each following week (weeks 2-7). Docetaxel 20 mg/m2 was administered weekly on day 1 from week 2-7. Radiotherapy consisted of 0.5 Gy/fraction BID at least 6 hours apart on days 2 and 3 of weeks 2-7 for a total dose of 12 Gy.
Nine patients were screened, 5 patients were enrolled, and 4 patients were treated between October 2013 through February 2015. After completion of salvage treatment per protocol, at 1 month follow up, partial response was seen in 2 patients (50%), stable disease in 1 patient (25%), and progressive disease in 1 (25%) patient. By 6 months, all patients had progressive disease, 1 patient (25%) completed a full course of re-irradiation, and 1 patient (25%) received further chemotherapy for progression. Treatment-related morbidity was limited to diffuse grade 1 skin toxicity reported in all patients. The Data Safety and Monitoring Board suggested closing this protocol as clinical response approached the predefined futility endpoint for complete response.
Low-dose radiotherapy in addition to docetaxel and cetuximab was well tolerated although treatment effects were transient. More durable treatment options may exist for definitive treatment; however, this protocol may offer palliation to select patients.
Local/regional failure after definitive radiotherapy (RT) remains a significant problem particularly in advanced stage head and neck cancer.1-3 Approximately 50% to 60% of patients who fail initial definitive treatment will die as a direct consequence of locally or regionally recurrent disease.1,2,4
Surgical salvage is sometimes successful, but not always feasible due to disease extent, location, or patient comorbidities.5
For these patients, systemic therapy, re-irradiation, and supportive care may be the only remaining options.6-9