Integrating Metronomic Therapy With Standard Chemotherapy in Advanced Unresectable Head and Neck Cancer: A Randomized Trial Addressing Global Cancer Care Equity (METRO PLUS)

Purpose: Advanced head and neck squamous cell carcinoma (HNSCC) carries a poor prognosis, particularly in resource-limited settings with restricted access to targeted or immune therapies. We evaluated whether adding triple oral metronomic chemotherapy (OMCT; erlotinib, celecoxib, methotrexate) to paclitaxel-carboplatin (PC) improves overall survival (OS) in patients with platinum-sensitive, unresectable advanced HNSCC. This was a single-center, investigator-initiated, prospective, randomized, open-label, phase III superiority trial conducted at a tertiary cancer center in North India.

Patients and methods: A total of 238 adults with histologically confirmed, unresectable advanced HNSCC eligible for palliative platinum-based chemotherapy were randomly assigned 1:1 after stratification by tumor site and Eastern Cooperative Oncology Group (ECOG) performance status. Arm A received PC plus OMCT; Arm B received PC alone. The primary end point was OS. Secondary end points included progression-free survival (PFS), quality of life (QoL; European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Functional Assessment of Cancer Therapy-Head & Neck), and safety.

Results: Among 238 patients (119 per arm), the median age was 47 years; 97.8% were male, and 78% had ECOG performance status (PS) 0-1. The median OS was 10 months (95% CI, 8.3 to 11.7) with PC + OMCT versus 5 months (95% CI, 3.9 to 6.1) with PC alone (hazard ratio [HR], 0.54 [95% CI, 0.41 to 0.72]; P <.001). The median PFS was 6 months versus 2 months, respectively (HR, 0.38 [95% CI, 0.28 to 0.50]; P <.001). QoL analyses demonstrated clinically meaningful preservation across multiple domains in the PC + OMCT arm. Grade ≥3 toxicities did not increase with the addition of OMCT.

Conclusion: In platinum-sensitive advanced HNSCC, the addition of triple OMCT to PC significantly improved OS and PFS with acceptable toxicity. PC + OMCT represents a feasible and cost-conscious first-line option in resource-constrained settings.

Indexed on Europe PMC as PubMed record 42308452 (DOI 10.1200/go-25-00721). Matched by DOI alone: one trial page and one institution page cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.