A single-arm feasibility phase II study of EMF (erlotinib + methotrexate + 5-fluorouracil) regimen in platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC)

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is a huge burden in India with the majority of patients presenting in advanced unresectable stages. Innovative, low-cost but efficacious regimens that can be easily administered in the outpatient setting are the need of the hour. We envisaged assessing whether a readily available triplet therapy of erlotinib + methotrexate + 5-fluorouracil (EMF) is efficacious in terms of extending life and maintaining the quality of life in such patients. Patients and methods:This was a single-arm, phase II, investigator-initiated interventional study. Thirty-five platinum-resistant/refractory patients of HNSCC were treated with a combination of erlotinib 150 mg, methotrexate 40 mg/m 2 (d1, d8) and 5-fluorouracil 500 mg/m 2 (d1, d8) every 28 days till progression or unacceptable toxicities. The primary endpoint was overall response rates (ORRs) at 3 months; additional endpoints were disease control rate (DCR) at 3 months, overall survival (OS) and progression-free survival (PFS), safety and patient-reported quality of life. Results:The ORR and DCR at 3 months were 45.7% and 68.5%, respectively. The PFS was 5 months (95% confidence interval (95% CI): 3.9-6 months) and the OS was 9 months (95% CI: 7.4-10.5 months). The 3-and 6-month PFS rates were 86% ± 6% and 45% ± 9%, respectively, while the OS rates at 3 and 6 months were 91% ± 5% and 68% ± 8%, respectively. Rash, mucositis and fatigue were common adverse events occurring in 23 (65%), 14 (40%) and 9 (25.7%), respectively. The most common grade 3 events seen were rash in 5 (14.2%) and diarrhoea in 2 (5.7%). Clinically significant improvement from baseline was seen in many domains of Quality of Life Core Questionnaire and Quality of Life Head and Neck Module. Research

Role of circulating tumour cells (CTCs) in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)

“…Our study reports CTC as a biomarker in recurrent/metastatic HNSCC, which is a difficult scenario but an unmet need. The detailed characteristics of the patients recruited have been elaborated in our previous study [ 16 ]. The CTCs clearance at 3 months of palliative chemotherapy (EMF: erlotinib + methotrexate + 5-Flourouracil) has been associated with a better PFS (6 months versus 4 months) and OS (10 months versus 8 months) numerically.…”

“…Response assessment was done at 3 monthly intervals using contrast-enhanced computed tomography (CECT)-face/neck/chest and response was evaluated using RECIST 1.1. The primary objective was to assess the objective response rates of the regimen, which has been reported previously by our group [ 16 ]. Here we report the secondary objective of the study that was to assess the role of CTCs as a surveillance biomarker for disease recurrence and metastasis.…”

Molecular pathways and targeted therapies in head and neck cancers pathogenesis

“…Some small molecular inhibitors of EGFR are also under investigation for the management of HNSCC, including selective inhibitors (e.g., gefitinib, erlotinib) ( 80 , 81 , 105 , 106 ) and dual-target inhibitors (e.g., afatinib, lapatinib, and dacomitinib) ( 82 , 107 ).…”

A FACS-based novel isolation technique identifies heterogeneous CTCs in oral squamous cell carcinoma

“…Thus, size-based approaches that exploit the bigger CTCs with respect to haematogenous cells for their isolation might miss the isolation of small-sized CTCs ( 8 ), which we have documented in our previous study on oral squamous cell carcinoma (OSCC) patients ( 9 ). Studies have shown the prognostic role of CTCs in head and neck squamous cell carcinoma (HNSCC) including OSCC ( 10 , 11 ).…”