DOI: 10.4103/jcot.jcot_9_26 ISSN: 3050-5763

Exploring the Impact of Oral Metronomic Chemotherapy in Advanced Head and Neck Cancers: Experience from a Regional Cancer Center of Eastern India

Debarshi Lahiri, Debjit Ghosh, Ranti Ghosh, Palas De, Bodhisattwa Dutta, Tapas Maji, Kushal Sen, Debanjan Chakraborty, Aniruddha Dam, Suparna Mazumder, Jayanta Chakrabarti, Arit Bhattacharjee, Sagnik Das, Sukalita Mallick, Atrayee Mukherjee, Ayan Das
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Abstract

Background:

Head and neck squamous cell cancers (HNSCCs) represent a major health burden in India, with high incidence and mortality driven by widespread tobacco use, limited awareness, and restricted access to treatment. Conventional chemotherapy carries significant toxicities, rendering it unsuitable for frail patients and those with comorbidities—particularly in low- and middle-income countries. Most patients at government-funded cancer centers cannot afford cetuximab or immunotherapy, and many decline injectable chemotherapy owing to social stigma and fear of adverse effects. Oral metronomic chemotherapy (OMCT) represents a potentially less toxic and cost-effective alternative. This study aimed to evaluate the association of OMCT with disease control and quality of life (QoL) in patients with advanced or recurrent HNSCC at a tertiary cancer center in Eastern India.

Materials and Methods:

This single-arm, retrospective observational study (Strengthening the Reporting of Observational Studies in Epidemiology-compliant) enrolled 184 patients with locally advanced, recurrent, or metastatic HNSCC who received OMCT (oral methotrexate, celecoxib, and gefitinib or erlotinib) between January 2024 and May 2025, with data collection concluding in May 2026. Of these, 160 patients with complete 12-month follow-up data were included in the efficacy analysis. Time to progression (TTP) was assessed using the Kaplan–Meier method. QoL was evaluated with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Head and Neck Cancer Module (35 items) questionnaire at baseline, 3, 6, 9, and 12 months. Friedman’s test (degrees of freedom = 4) was used to assess longitudinal QoL changes across the five timepoints, with effect sizes reported as Kendall’s W . Toxicity was graded per Common Terminology Criteria for Adverse Events, version 5.0.

Results:

The cohort had a mean age of 55.5 ± 13.9 years; 132 (71.7%) were male. At baseline, 140 (76.1%) had stage IVA disease. Friedman’s test demonstrated statistically significant changes in 14 of 18 QoL domains; however, HNNU was excluded from clinical interpretation because baseline values were universally zero, leaving 13 clinically meaningful QoL improvements. The largest effects were observed for painkiller use [69.0% reduction; χ 2 (4) =369.232, P < 0.001, Kendall’s W = 0.584] and pain [73.0% reduction; χ 2 (4) =356.207, P < 0.001, W = 0.557]. Disease control was achieved in 121 of 160 analyzed patients (75.6%); 6 (3.8%) became operable, and 28 (17.5%) were escalated to radical chemoradiation. The median TTP was not reached within the 12-month observation period; the restricted mean survival time at 12 months was 9.79 months (95% confidence interval [CI]: 9.21–10.37). The 12-month event-free rate was 71.2% (95% CI: 63.6%–77.6%; N = 160). Seven deaths were documented during the observation period. No Grade 4 toxicities were reported.

Conclusion:

In this observational cohort, OMCT was associated with statistically significant and clinically meaningful improvements in QoL across multiple domains, and with satisfactory disease control in patients with advanced HNSCC who were unable or unwilling to receive standard systemic therapy. Its low toxicity profile and potential bridging role toward curative-intent treatment warrant evaluation in prospective randomized trials. These findings support OMCT as a feasible option in resource-constrained settings where standard therapies are inaccessible.

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