Chemotherapy in Combination With Methionine Restriction Induced A Complete Response in a Patient With Recurrent Metastatic Tongue Squamous-Cell Carcinoma.

Abstract

Background/aim: Recurrent head and neck squamous-cell carcinoma (HNSCC) is associated with poor prognosis and limited treatment options, particularly after failure of standard therapies including surgery, radiotherapy, chemotherapy, and immune checkpoint inhibitors. Methionine restriction has emerged as a novel clinical metabolic therapeutic strategy targeting the methionine addiction of cancer cells. The present patient report describes a case of recurrent tongue HNSCC that achieved complete remission with chemotherapy combined with methionine restriction.

Case report: A 35-year-old man was diagnosed with HNSCC of the left lateral border of the tongue (cT2N2bM0, Stage IVA). The patient underwent curative-intent surgery consisting of partial glossectomy and neck dissection. Despite multimodal treatment, including induction chemotherapy, salvage surgery, postoperative chemoradiotherapy, and subsequent immune checkpoint inhibitor therapy, the tumor recurred in the left submandibular region. Following further progression, combination chemotherapy with paclitaxel and cetuximab was administered in combination with methionine restriction (MR), consisting of a low-methionine diet and oral recombinant methioninase (rMETase), rMETase was produced using recombinant Escherichia coli expressing the methioninase gene from Pseudomonas putida and purified by standard methods. Tumor metabolic activity was evaluated using [¹⁸F]fluorodeoxyglucose positron-emission tomography (PET)/computed tomography (CT) performed according to standard clinical protocols. Rapid tumor regression was observed. Follow-up magnetic resonance imaging (MRI) and PET/CT demonstrated complete response, which was maintained after de-escalation to cetuximab combined with MR.

Conclusion: The present case demonstrates the potential clinical efficacy of combining chemotherapy with MR in the treatment of recurrent HNSCC after curative-intent surgery and failure of standard therapies, including immune checkpoint inhibition. MR may represent a promising metabolic therapeutic approach for refractory HNSCC. Αdditional cases and prospective clinical trials are necessary.