International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationCould the Addition of Cetuximab to Conventional Radiation Therapy Improve Organ Preservation in Those Patients With Locally Advanced Larynx Cancer Who Respond to Induction Chemotherapy? An Organ Preservation Spanish Head and Neck Cancer Cooperative Group Phase 2 Study
Introduction
The first study evaluating the possibility of avoiding total laryngectomy (TL) in patients with locally advanced laryngeal cancer was published 25 years ago (1). Induction chemotherapy (IC) followed by conventional radiation therapy (RT), in those patients who had responded, demonstrated organ preservation without significantly affecting overall survival.
A decade later, the usefulness of IC was questioned when a published article reported the first results of the Radiation Therapy Oncology Group (RTOG) 91-11 study (2), claiming that concomitant treatment with RT and cisplatin was superior in locoregional control and larynx preservation. These data were consistent with the results of the meta-analysis on the use of chemotherapy published a few years earlier (3), and as a result, most institutions changed their approach to larynx preservation from IC to concomitant chemotherapy.
Optimization of IC produced by introducing docetaxel (Taxotere, T) to the classic platinum plus fluorouracil (PF) scheme 4, 5 enabled its use in organ preservation protocols, and the GORTEC (Groupe d'Oncologie Radiothérapie Tête Et Cou) group demonstrated that the 3-drug schedule with TPF was clearly superior to PF for larynx preservation (6).
Cetuximab is a chimeric monoclonal antibody that binds with high affinity to the extracellular domain of the epidermal growth factor receptor and induces antibody-dependent cellular cytotoxicity (7). The combination of cetuximab plus RT has demonstrated superior efficacy and has only slightly increased toxicity as compared with RT alone (8).
Cetuximab combined with RT seems to be as effective as cisplatin in organ preservation, with a different pattern of acute toxicity after induction with TPF (9), which could result in higher rates of larynx preservation. The aim of our study was to evaluate survival with functional larynx (SFL) after RT plus cetuximab in patients who respond to IC with TPF.
Section snippets
Study patients
From October 2008 to February 2011, previously untreated patients between 18 and 70 years of age with stage III and IVA squamous cell carcinoma of the larynx, and candidates for TL according to each local multidisciplinary committee, were included in this trial. Patients were followed up until May 2015. The protocol was approved by all institutional review boards at the participating institutions, and all the patients provided written, informed consent.
Study design and treatment
This was a prospective, multicenter, phase
Patient characteristics
A final total of 94 patients were enrolled in the study (see Fig. 1 for intent-to-treat population), and 1 patient was excluded because he did not fulfill 1 of the inclusion criteria (renal insufficiency) and therefore did not start IC. Demographic, clinical, and pathologic characteristics of the modified intent-to-treat population (n=93) are represented in Table 1. The following factors are also worth mentioning: the limited inclusion of women (8%), the high proportion of supraglottic
Discussion
All trials investigating organ preservation that have used an IC arm have also used RT alone as the local treatment in patients who demonstrated an almost PR 1, 2, 6, 13. Our study was designed to evaluate the role of cetuximab added to RT in maintaining locoregional control and reducing chronic toxicity (pharyngo-larynx functionality). We found that BRT with cetuximab was superior to the use of RT alone in locoregional control (8), and possibly also in larynx preservation (14). Controversy
Acknowledgments
The authors thank Eva Uson, statistician from TFS, and Juan Carlos Adansa from the TTCC: Spanish Head and Neck Cancer Cooperative Group, for their continuous support during the development of this clinical trial; Crystal Freeman for her support in reviewing the English; and the patients and families who participated in this trial.
References (20)
- et al.
Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data—MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer
Lancet
(2000) - et al.
CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC, RTOG consensus guidelines
Radiother Oncol
(2003) - et al.
Proposal for the delineation of the nodal CTV in the node-positive and the post-operative neck
Radiother Oncol
(2006) - et al.
Larynx preservation clinical trial design: Key issues and recommendations. A consensus panel summary
Int J Radiat Oncol Biol Phys
(2009) - et al.
Late toxicity after radical treatment for locally advanced head and neck cancer
Oral Oncol
(2015) Induction chemotherapy plus radiation in patients with advanced laryngeal cancer
N Engl J Med
(1991)- et al.
Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer
N Engl J Med
(2003) - et al.
Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer
N Engl J Med
(2007) - et al.
Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer
N Engl J Med
(2007) - et al.
Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation
J Natl Cancer Inst
(2009)
Cited by (17)
Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India<sup>✰</sup>
2021, Cancer Treatment and Research CommunicationsCitation Excerpt :In a subgroup analysis, taking the effects of treatment and adverse events into consideration, cetuximab plus RT showed superior responses regarding OS and PFS in HPV-positive patients of primary oropharyngeal SCC [62]. An organ preservation Phase II study by the Spanish Head And Neck Cancer Cooperative Group showed that cetuximab with RT could improve functional larynx preservation in patients with stage III and IVA laryngeal cancers who responded to docetaxel, cisplatin, and 5-FU [63]. Bonner et al. (2016) reported laryngeal preservation rates were 87.9% at 2 and 3 years in the cetuximab plus RT group compared with 85.7% at 2 years and 76.8% at 3 years in the RT alone group with an HR of 0.57 (95% CI, 0.23–1.42; P = 0.22).
Nutritional changes in patients with locally advanced head and neck cancer during treatment
2017, Oral OncologyCitation Excerpt :HNSCC patients are specially at high risk of malnutrition due to tumor site and treatment [7]. In recent years antineoplasic treatments have contributed to improve locoregional control and survival [8,9], however, acute toxicity caused by these treatments may exacerbate nutritional deterioration by compromising dietary intake by odynodysphagia (mucositis related), anorexia or xerostomia [10]. The prevalence of malnutrition in HNSCC patients at diagnosis ranges from 42 to 77% and worsen throughout the treatment [11,12].
The Not Knowing Is the Hardest Part
2017, International Journal of Radiation Oncology Biology PhysicsRole of sarcopenia on survival and treatment-related toxicity in head and neck cancer: a narrative review of current evidence and future perspectives
2023, European Archives of Oto-Rhino-Laryngology