Randomized Controlled Study Comparing Efficacy and Toxicity of Weekly vs. 3-Weekly Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

Abstract

Background: Head and Neck Cancer is a major public health problem in India, majority of which are lifestyle related, male predominant requiring dedicated infrastructure and human resource. The 5-year survival is 59% for all stages combined and only 45% in patients with locally advanced inoperable head and neck cancer using current chemoradiation schedules. Chemotherapy agents administered in the induction or concurrent setting comprise of taxanes (Docetaxel, paclitaxel), platinum compounds (Cisplatin, carboplatin) and fluorouracil (TPF). For patients with advanced Head and neck squamous cell carcinoma (HNSCC), 3-weekly TPF regimen is the established standard induction chemotherapy (ICT) option based on overall survival benefit. However, TPF regimen is known to be associated with significant dose limiting toxicities which may impair tolerance and effectiveness of therapy. In this study we assessed the efficacy and toxicity of weekly vs. 3-weekly Docetaxel, Cisplatin, and Fluoro-uracil (TPF) induction chemotherapy in locally advanced Head and neck squamous cell carcinoma (LA-HNSCC). Methods: This was an open labeled randomized two arm study with 41 patients in the 3-weekly TPF arm and 41 patients in the weekly arm. Patients were randomized using numbers from a randomization software, data recorded, and results were analyzed. Results: The weekly group achieved far greater symptom relief than 3-weekly group (72 vs. 64%). The overall response rates were similar in both arms (ORR 75.6 and 73.1% in the weekly and 3-weekly groups, respectively). Renal toxicity was significantly lower in the weekly group as compared to 3 weekly arm post three cycles of chemotherapy (CrCl 91.49 ml/min vs. 76.67 ml/min, respectively). The weekly group had predominantly grade I and II neutropenia (19.5 and 17.1%, respectively) as compared to 3-weekly group where grade III and IV neutropenia (31 and 12%, respectively) was more prominent (p-0.003). Among non-hematological toxicities, mucositis, nausea/vomiting, and diarrhea in the weekly group were significantly lower when compared to 3-weekly group. Progression free survival was slightly higher in the weekly group (18 months) when compared to 3-weekly group (15 months) which was not statistically significant. Conclusion: Weekly induction with TPF had lower toxicity and similar efficacy as compared to 3-weekly regimen in locally advanced HNSCC patients. Myelosuppression, which was the most serious and common complication of 3-weekly TPF regimens was notably low using the weekly regimen. Our results suggest that weekly TPF regimen may be a safer and effective alternative to 3-weekly TPF for treatment of LA-HNSCC. To our knowledge this is the first study reporting the efficacy of weekly TPF regimen in LA-HNSCC till date.

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group

“…To decrease TPF toxicity without changing efficacy, modified schedule of TPF has been proposed. But, data from randomized trial are currently limited and results mixed [133,134]. Better selection tools to identify patients who will benefit from TPF induction remain needed.…”

A Randomized Study Analyzing Clinical and Dosimetric Outcome in Locally Advanced Head-and-Neck Cancer Treated With Conformal Chemoradiation With or Without Induction Chemotherapy

“…In this study, we have modified the conventional induction treatment plan using a 1-day slow infusion of 5FU as per institutional logistics. There have been attempts to use a modified TPF regimen to decrease its toxicity without altering the efficacy, but the available data are scarce and mixed [16,17]. Accelerated repopulation is also a noted radiobiological concern in head-and-neck squamous cell cancer, to address this issue, we started CTRT 2 weeks after completion of induction TPF, while several trials used a 3-5-week gap.…”

Efficacy and safety of weekly versus triweekly cisplatin treatment concomitant with radiotherapy for locally advanced nasopharyngeal carcinoma: A systematic review and pooled analysis

“…Accordingly, minimizing adverse effects during treatment is an important goal for clinical oncologists. In recent years, increasing evidence has indicated that weekly chemotherapy has similar efficacy and lower toxicity than triweekly regimens for many types of cancers ( Schuette et al, 2005 ; Dessai et al, 2016 ; Tousif et al, 2020 ). Multiple studies have compared the outcomes of weekly and triweekly cisplatin concurrent chemoradiotherapy (CCRT) in advanced head and neck squamous cell carcinoma (HNSCC) ( Espelia et al, 2012 ; Geiger et al, 2014 ; Tsan et al, 2012 ).…”