Baa Annie Kanchan, Sharma Atul, Bhaskar Suman, Biswas Ahitagni, JeeBharti Sacchidanand, Thakar Alok, Kumar Rajeev, Pramanik Raja
Department of Medical Oncology, Dr B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India.
Department of Radiation Oncology, Dr B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi 110029, India.
Ecancermedicalscience. 2022 Sep 29;16:1451. doi: 10.3332/ecancer.2022.1451. eCollection 2022.
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.
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/m2 (d1, d8) and 5-fluorouracil 500 mg/m2 (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.
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.
The triplet regimen of EMF is a feasible and safe therapeutic option in patients with platinum-resistant/refractory HNSCC. It has demonstrated favourable response rates and improvement in quality of life; however, a randomised phase III study would add more robust value (NCT: CTRI/2020/02/023378).
头颈部鳞状细胞癌（HNSCC）在印度是一个巨大的负担，大多数患者就诊时已处于晚期不可切除阶段。当下需要创新、低成本且有效的治疗方案，以便能在门诊轻松实施。我们设想评估一种现成的三联疗法——厄洛替尼+甲氨蝶呤+5-氟尿嘧啶（EMF）在延长此类患者生命和维持生活质量方面是否有效。
这是一项由研究者发起的单臂、II期干预性研究。35例铂耐药/难治性HNSCC患者接受厄洛替尼150 mg、甲氨蝶呤40 mg/m²（第1天、第8天）和5-氟尿嘧啶500 mg/m²（第1天、第8天）联合治疗，每28天一次，直至疾病进展或出现不可接受的毒性反应。主要终点是3个月时的总缓解率（ORR）；其他终点包括3个月时的疾病控制率（DCR）、总生存期（OS）和无进展生存期（PFS）、安全性以及患者报告的生活质量。
3个月时的ORR和DCR分别为45.7%和68.5%。PFS为5个月（95%置信区间（95%CI）：3.9 - 6个月），OS为9个月（95%CI：7.4 - 10.5个月）。3个月和6个月时的PFS率分别为86%±6%和45%±9%，3个月和6个月时的OS率分别为91%±5%和68%±8%。皮疹、黏膜炎和疲劳是常见的不良事件，分别有23例（65%）、14例（40%）和9例（25.7%）发生。最常见的3级事件是5例（14.2%）出现皮疹，2例（5.7%）出现腹泻。生活质量核心问卷和头颈部生活质量模块的许多领域从基线水平有了具有临床意义的改善。
EMF三联疗法对于铂耐药/难治性HNSCC患者是一种可行且安全的治疗选择。它已显示出良好的缓解率和生活质量改善；然而，一项随机III期研究将增加更强有力的价值（临床试验注册号：CTRI/2020/02/023378）。
