Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced head and neck cancer (LAHNSCC)
Introduction
Treatment with chemoradiation is an accepted standard for locally advanced head and neck squamous cell carcinoma (LAHNSCC). The addition of concurrent chemotherapy to radiotherapy (RT) for LAHNSCC results in an absolute survival benefit of 6.5% at 5-years, with greater benefit with platinum-based chemotherapy [1]. Among the concurrent platinum agents, single-agent cisplatin is superior to single-agent carboplatin and equivalent to carboplatin with 5-fluorouracil (5FU) in retrospective analyses [2], [3].
Although chemoradiation with high-dose cisplatin improves survival versus RT alone, it is associated with higher toxicity [4]. Therefore less toxic agents that will achieve equivalent or superior outcomes have been sought. Bonner et al. reported that cetuximab/RT resulted in improved locoregional control and survival with little increase in toxicity compared with RT alone [5]. This led to the adoption of cetuximab as one alternative to cisplatin concurrent with RT for LAHNSCC. Although cisplatin is still the most commonly used agent (51%), cetuximab is being used in approximately 20% of patients [6].
Importantly, the study by Bonner was conducted when RT alone was still an accepted standard for LAHNSCC. Only recently has cetuximab/RT been compared to concurrent platinum/RT in prospective randomized trials, although results are not yet reported. Our initial retrospective report showed that concurrent cisplatin/RT versus cetuximab/RT was associated with superior locoregional control, failure-free survival, and overall survival [7]. Nonetheless, unmeasured confounders limited this study. Prior to FDA approval of cetuximab for LAHNSCC, non-cisplatin candidates were routinely treated with alternative platinum-based regimens, namely, 5FU/carboplatin [8] at our center. We hypothesized that characteristics of these patient groups would be similar and hence we sought to compare the outcomes of concurrent IMRT with high-dose cisplatin, 5FU/carboplatin, or cetuximab.
Section snippets
Study design
In this Institutional Review Board-approved (WA0654-10) study, we retrospectively identified patients with a diagnosis of LAHNSCC of the oropharynx, hypopharynx, or larynx treated with curative intent with IMRT and concurrent cisplatin, 5FU/carboplatin, or cetuximab, from 11/02 to 4/08. Reasons for exclusion were surgery to the primary site, prior RT for a non-basal cell carcinoma of the head and neck, induction or adjuvant chemotherapy, weekly cisplatin, or prior active malignancy. Three
Study population
Characteristics of all patients are shown in Table 1. Patient selection for cetuximab or 5FU/carboplatin, respectively, was based on the following factors: audiogram/poor hearing (30.6% and 53.8%), renal insufficiency (4.1% and 9.6%), cardiac history (2.0% and 1.9%), performance status (16.3% and 3.8%), patient preference (16.3% and 5.8%), neuropathy (4.1% and 9.6%), and a combination of factors (24.5% and 15.4%). Treatment groups were balanced with regard to all factors except age, KPS,
Discussion
Concurrent treatment with cetuximab and IMRT for LAHNSCC was associated with inferior OS, LRFS, and DMFS versus concurrent high-dose cisplatin or 5FU/carboplatin and IMRT in our series. Although 5FU/carboplatin and cetuximab patients had very similar pretreatment characteristics, cetuximab was associated with a 2.6-fold increased risk of death (P = .005). Furthermore, treatment with cetuximab but not 5FU/carboplatin resulted in significantly higher rates of LRF than cisplatin. These findings were
Conflicts of interest statement
Eric J. Sherman has consulted for Bristol-Myers-Squibb.
Other conflicts of interest: None declared.
References (25)
- et al.
Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients
Radiother Oncol
(2009) - et al.
Concurrent chemoradiation with carboplatin-5-fluorouracil versus cisplatin in locally advanced oropharyngeal cancers: is more always better?
Int J Radiat Oncol Biol Phys
(2010) - et al.
Concurrent cisplatin and radiation versus cetuximab and radiation for locally advanced head-and-neck cancer
Int J Radiat Oncol Biol Phys
(2011) - et al.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
J Chronic Dis
(1987) - et al.
Intensity-modulated radiotherapy in the treatment of oropharyngeal cancer: an update of the Memorial Sloan-Kettering Cancer Center experience
Int J Radiat Oncol Biol Phys
(2012) - et al.
Locoregionally advanced head and neck cancer treated with primary radiotherapy: a comparison of the addition of cetuximab or chemotherapy and the impact of protocol treatment
Int. J. Radiat. Oncol. Biol. Phys.
(2008) - et al.
Comparison of every 3 week cisplatin or weekly cetuximab with concurrent radiation therapy for locally advanced head-and-neck cancer: definitive management of head-and-neck squamous cell carcinoma
Int J Radiat Oncol Biol Phys
(2014) - et al.
Human papillomavirus as a marker of the natural history and response to therapy of head and neck squamous cell carcinoma
Semin Radiat Oncol
(2012) - et al.
Toxicity of cetuximab versus cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer (LAHNSCC)
Radiother Oncol
(2011) - et al.
Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival
Lancet Oncol
(2010)
An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer
J Clin Oncol
Cited by (50)
A Multicenter Evaluation of Different Chemotherapy Regimens in Older Adults With Head and Neck Squamous Cell Carcinoma Undergoing Definitive Chemoradiation
2024, International Journal of Radiation Oncology Biology PhysicsTo Shy Away From Chemotherapy Is to Compromise
2020, International Journal of Radiation Oncology Biology PhysicsThe art of suicidal molecular seduction for targeting drug resistance
2020, Medical HypothesesCitation Excerpt :Recent studies revealed equal potency for both of these agents and found neither of them superior to the other [73,81]. 5-fluorouracil (a suicide inhibitor [82]) of combination with carboplatin also proved to be as effective as the monoclonal antibody cetuximab in the treatment of locally-advanced head and neck cancer [83]. This example indicates that suicide inhibitors can be as effective as monoclonal antibodies (mAbs), and as a small-molecule, they are extremely more cost-effective.
- 1
Present address: Targeted Radiation Institute at VMOC, 5725 W. Las Positas Blvd, Suite 100, Pleasanton, CA 94588, USA.
- 2
Present address: Hudson Valley Oncology Associates, 19 Baker Ave, Suite 100, Poughkeepsie, New York 12601, USA.