Neoadjuvant Chemotherapy for Borderline Resectable Head and Neck Cancers: A Comparative Study of Three-Drug and Two-Drug Regimens in a Low- and Middle-Income Country (LMIC) Context

Background Borderline resectable head and neck squamous cell carcinoma (HNSCC) presents a significant therapeutic challenge, particularly in low- and middle-income countries (LMICs) like India. Neoadjuvant chemotherapy (NACT) aims to downstage tumors to achieve operability, but the optimal regimen remains controversial due to varying efficacy and toxicity profiles. This study compares the efficacy and toxicity of a three-drug regimen (TPF: docetaxel, cisplatin, and 5-fluorouracil) with a two-drug regimen (taxane and platinum) in patients with borderline resectable HNSCC in an LMIC setting. Methods In this retrospective cohort study, a total of 90 patients with borderline resectable HNSCC were included. Forty-three patients received the TPF regimen (Arm A), while 47 received the taxane + platinum regimen (Arm B). The outcomes measured included conversion to operability, stage-specific outcomes, overall survival (OS), progression-free survival (PFS), and treatment-related toxicity. Statistical analyses included chi-square tests for categorical variables, Kaplan-Meier survival analysis, and Cox proportional hazards modeling for multivariate analysis. Results The conversion to operability was significantly higher in the TPF group (72% vs. 51%, p=0.03). Patients in Arm A also exhibited a trend toward higher pathological complete response (pCR) rates compared to Arm B (60% vs. 43%, p=0.08). The overall survival and progression-free survival were improved in the TPF group, although the study did not reach statistical significance in these endpoints due to the limited sample size. However, the TPF regimen was associated with significantly higher toxicity. Grade 3-4 neutropenia occurred in 55% of the patients in Arm A compared to 32% in Arm B (p=0.01), and mucositis was observed in 47% of Arm A patients compared to 19% in Arm B (p=0.002). Febrile neutropenia was also more frequent in the TPF group (28% vs. 13%, p=0.04). Multivariate analysis identified the chemotherapy regimen (HR=1.45, 95% CI 1.05-2.01, p=0.02) and baseline nutritional status (HR=1.78, 95% CI 1.12-2.82, p=0.01) as independent predictors of overall survival. Conclusion While the TPF regimen offers superior efficacy in terms of tumor downstaging and conversion to operability, its higher toxicity profile limits its applicability in resource-constrained settings, such as LMICs. The taxane + platinum regimen, although less effective in downstaging, presents a more favorable toxicity profile, making it a viable alternative for patients with comorbidities or poor performance status. The choice between these regimens should be individualized, considering the patient's overall health, nutritional status, and the availability of supportive care. Further research is warranted to optimize NACT strategies for patients in LMICs.