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. 2010 May;24(2):137–147. doi: 10.1055/s-0030-1255331

The Role of Chemotherapy in the Management of Patients with Head and Neck Cancer

Panayiotis (Panos) Savvides 1
PMCID: PMC3324245  PMID: 22550434

Abstract

Recent advances in the management of patients with head and neck cancer point to an expanding role of chemotherapy, resulting in an increased involvement of the medical oncologist in the multidisciplinary care of these patients. This review focuses on patients with squamous cell carcinoma of the oral cavity, pharynx, and larynx. A comprehensive review of the clinical trial data that have defined new standards of care and a detailed presentation of widely used chemotherapeutic regimens, including both cytotoxic and molecularly targeted agents, are presented. Information on human papilloma virus–associated squamous cell cancer of the head and neck is presented, and implications in the clinical management of this subgroup of patients based on the epidemiologic and pathologic characteristics are discussed.

Keywords: Cancer of the head and neck, chemotherapy, squamous cell carcinoma

Approximately 48,000 new cases of head and neck cancer were expected in the United States in 2009 alone,1 and more than 600,000 new cases will be diagnosed worldwide. Head and neck cancer accounts for 3 to 4% of all cancer diagnoses in Western countries,2,3 and its incidence is higher in southeast Asia and in Africa where it accounts for 8 to 10% of all cancers.4 Overall, head and neck cancer represents the eighth most common cause of cancer death.

Historically, treatment of patients with squamous cell carcinoma of the head and neck (SSCHN) has primarily been driven by surgical interventions and continued advances in radiation therapy (RT) treatment planning and delivery. In this setting of complex treatment algorithms, recent advances in the management of patients with head and neck cancer point to an expanding role of chemotherapy and therefore an increased involvement of the medical oncologist in the multidisciplinary care of these patients.

The scope of this review is to provide a comprehensive description of expanding chemotherapeutic options, including both cytotoxic and molecularly targeted agents, that are applicable to patients diagnosed with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx. Data on patients diagnosed with cancer of the nasopharynx will be presented separately because of its distinct etiology, pathology, and response to treatment modalities.

Chemotherapy alone does not have curative potential. As a result, it does not have a defined role in the management of patients with early-stage disease (stages I and II) where single modality (surgery or RT) offers high cure rates, with 5-year overall survival (OS) rates around 85% for stage I SCCHN and around 70% for stage II disease.5,6,7,8 The remaining part of the review will therefore focus on describing the role of chemotherapy in the locally advanced (LA SCCHN) recurrent and metastatic settings.

Although the importance of site-specific characteristics in selecting the most appropriate combination modalities should not be underestimated, we purposely chose a concept-based approach to better address the continuity and evolution of treatment concepts (Fig. 1).

Figure 1.

Figure 1

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Treatment options involving chemotherapy for locally advanced squamous cell carcinoma of the head and neck.

ROLE OF CHEMOTHERAPY IN LA SCCHN

Chemotherapy with Concurrent RT in the Postsurgical Setting

In patients with LA SCCHN undergoing definitive surgery (stages III, IVa), local and regional recurrence rates remain significant (up to 50% at 2 years), distant metastases develop (up to 20% at 2 years), and 5-year survival rates are poor.9 Postoperative adjuvant RT in this setting has been used in patients with pathologic findings associated with high risk for locoregional recurrence.

In an attempt to further improve outcomes, the role of concurrent administration of cytotoxic chemotherapy during RT has been investigated in two phase III clinical trials where high-dose cisplatin (100 mg/m2) administered on days 1, 22, and 43 of concurrent RT was evaluated.10,11

In both trials, patients with LA SCCHN of the oral cavity, oropharynx, larynx, or hypopharynx were included. In the first trial conducted in Europe, an improvement in both OS as well as improved locoregional control was observed, favoring the addition of chemotherapy to concurrent RT treatment. In the trial conducted in the United States and coordinated by the Radiation Therapy Oncology Group (RTOG), an improvement in disease-free survival was documented, but it did not result in a statistically significant improvement in OS. Based on these findings, concurrent chemoradiation therapy (CRT) has become the new standard of care for patients with surgically resected tumors demonstrating high-risk features.

Precise definition of high-risk features remains a research question, as definitions were not identical in the two trials. More specifically, in the European trial, high-risk features included pathologically defined advanced primary tumors (pT3 or pT4) and any nodal stage (N), except T3N0 of the larynx with negative resection margins, or an early primary tumor (pT1 or pT2) with an advanced nodal stage (N2 or N3) and no distant metastasis (M0). Patients with early-stage primary tumor (pT1 or pT2) and nodal stage (N0 or N1) who had unfavorable pathology findings (extranodal spread, positive resection margins, perineural involvement, or vascular tumor embolism) were also eligible, as were patients with oral cavity or oropharyngeal primary tumors with involved lymph nodes at level IV or V. In the RTOG trial, the presence of any or all of the following features allowed patients to meet eligibility criteria: histologic evidence of invasion of two or more regional lymph nodes, extracapsular extension of nodal disease, and microscopically involved mucosal margins of resection.

In an attempt to identify the subgroup of patients most likely to benefit from concurrent CRT, a retrospective pooled analysis of data of individual patients was undertaken,12 which revealed that positive margins and/or extracapsular spread of tumor from involved lymph nodes were the most significant prognostic factors for poor outcome. As a result, consensus recommendations, currently endorsed by the National Comprehensive Cancer Network (NCCN) Head and Neck Committee, identifies this subgroup of patients at high risk for recurrence, and addition of chemotherapy to adjuvant RT represents the current standard of care. Additional high-risk features included in the eligibility criteria of these trials as well as retrospective analyses undertaken using other data sets (pT3 or pT4 primary, N2 or N3 nodal disease, nodal disease in levels IV or V, perineural invasion, vascular embolism)13,14,15 can still be considered on a case by case basis in making adjuvant RT versus concurrent chemotherapy and RT recommendations.

Induction Chemotherapy in the Management of Patients with LA SCCHN

As early clinical trials in the metastatic setting established that SCCHN is a chemosensitive disease, attempts were initiated to evaluate the additional benefit in improved locoregional control and decreased incidence of metastatic disease by the addition of chemotherapy prior to surgery or RT. In theory, induction chemotherapy offers several advantages, including decreasing the size of the primary tumor and nodal metastases allowing improved efficacy and potentially less local toxicity after the subsequent use of either surgery or RT and reducing/eliminating potential sites of distant micrometastases.16,17,18

The landmark trial that validated induction chemotherapy is the Department of Veterans Affairs Laryngeal Cancer Study Group trial,19 which compared total laryngectomy to organ preservation with induction chemotherapy followed by RT. This study also established the use of the cisplatin and 5-fluorouracil (5-FU) combination regimen, which remained the standard of care regimen for induction chemotherapy until improved induction chemotherapy outcomes were demonstrated with the addition of a taxane to the cisplatin and 5-FU backbone.

The efficacy of induction chemotherapy followed by RT compared with that of RT alone was evaluated in a meta-analysis that documented that there was no survival benefit of adding induction chemotherapy to RT alone when all induction regimens were included in the meta-analysis; however, a statistically significant benefit could be established (hazard ratio = 0.88, 95% CI, 0.79 to 0.97) when only platinum and 5-FU combination regimens were examined.20

More recently, multiple trials have shown that the addition of a taxane to the cisplatin and 5-FU backbone results in improved outcomes. Docetaxel has been added to cisplatin and 5-FU (TPF regimen) both as an organ preservation study as well as in patients with LA unresectable SCCHN.21,22 In the setting of an organ preservation strategy, the addition of docetaxel resulted in a statistically significant 3-year laryngeal preservation rate (70% vs. 58%), and in the unresectable SCCHN setting the addition of docetaxel resulted in an improvement in both progression-free survival (PFS) as well as OS (11 vs. 8.2 months, and 18.8 vs. 14.5 months, respectively). Paclitaxel-containing induction regimens have also been evaluated and have demonstrated improved outcomes.23,24

Finally, induction chemotherapy has been used as a tool to guide subsequent modality selection. In this setting, a cycle of induction chemotherapy is administered followed by administration of definitive concurrent CRT to responders, whereas nonresponders undergo surgery. This approach has been successful in patients with LA SCC of the larynx,25 but the same strategy has not been successful in patients with oropharyngeal26 and oral cavity27 primary tumors. Given mixed results, this approach remains investigational and should not be used outside of a clinical trial setting.28

Concurrent CRT

The Department of Veterans Affairs laryngeal trial established that an organ preservation strategy using induction chemotherapy followed by definitive RT results in an OS survival comparable with that of primary surgical resection.19

Subsequent clinical research, including the landmark intergroup RTOG study 91–11, attempted to define the most effective organ preservation strategy. This three-arm study in patients with LA SCC of the larynx compared RT alone to concurrent CRT and to induction chemotherapy followed by definitive RT.29,30 A total of 547 patients were included in the study, and, after a median follow-up period of 3.8 years, RT with concurrent administration of cisplatin was found to be superior to induction chemotherapy followed by RT or RT alone for laryngeal preservation (88% vs. 75% vs. 70%, respectively) and locoregional control (78% vs. 61% vs. 56%, respectively).

The chemotherapeutic agent is high-dose cisplatin (100 mg/m2), administered concurrently with RT on days 1, 22, and 43. However, cisplatin administration is associated with significant toxicities (Table 1).Therefore, alternative cytotoxic chemotherapy regimens have been tried in select patient populations, including weekly cisplatin protocols, substitution with carboplatin, and combination cisplatin/carboplatin with a taxane of 5-FU, supported by limited clinical trial data and included in the NCCN Head and Neck Committee guidelines.

Table 1.

Commonly Used Chemotherapeutic Regimens

Chemotherapy Dose, Frequency, Number of Cycles Selected Adverse Events References
Cisplatin (P) (Every 3 weeks, RT days 1, 22, 43) (Grade 3–5 increased frequencies, compared with control arm, occurring in more than 10% of patients) Nausea/vomiting (12–40%) Neutropenia (13%) Infection (12%) Peripheral neuropathy (10%) 10, 11, 29
P: 100 mg/m2 on day 1 Nausea/vomiting (12–40%)
Neutropenia (13%)
Infection (12%)
Peripheral neuropathy (10%)
Cetuximab Loading dose: 400 mg/m2 (4–10 days prior to RT) (Grade 3–5 increased frequencies) 32, 44, 60, 78
Maintenance: 250 mg/m2 (weekly during RT) Infusion reactions (3%)
Acneiform rash (17%)
Hypomagnesemia
TPF (TAX 324) (Every 3 weeks for 3 cycles) (Grade 3 or 4 frequencies) 33
Docetaxel (T) T: 75 mg/m2 on day 1 Neutropenia (33%)
Cisplatin (P) P: 100 mg/m2 on day 1 Infection (7%)
5-FU (F) F: 1000 mg/m2 CI days 1–4 Febrile neutropenia (5%)
TPF (European) (Every 3 weeks for 4 cycles) (Grade 3 or 4 frequencies) 21
Docetaxel (T) T: 75 mg/m2 on day 1 Neutropenia (77%)
Cisplatin (P) P: 75 mg/m2 on day 1 Alopecia (12%)
5-FU (F) F: 750 mg/m2 by CI days 1–5 Infection (7%)
Febrile neutropenia (5%)
Cisplatin (P) P: 100 mg/m2 on day 1 Nausea/vomiting (7–14%) 19, 21, 33, 87
5-FU (F) F: 1000 mg/m2 by CI days 1–5 Hematologic (52–56%)
Infection (5–6%)
Peripheral neuropathy (1–4%)
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CI, continuous infusion; 5-FU, 5-fluorouracil; RT, radiation therapy.

Meta-analyses have compared the efficacy of concurrent CRT to RT alone and have consistently demonstrated improved efficacy for the concurrent CRT approach. For platinum including chemoradiation protocols, an improved OS of 8 to 11% has been demonstrated in both surgically resectable patients and unresectable patients.31 Based on these findings, concurrent CRT is considered the standard of care.

Cetuximab, a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), is currently approved for use with RT in patients with LA SCCHN, based on phase III clinical trial data comparing RT alone to concurrent RT and cetuximab, which documented a statistically significant improvement in OS for the combination arm.32 This is analyzed in detail in the later section “Molecularly Targeted Agents in LA SCCHN.” No direct comparisons of a cytotoxic agent to a targeted agent when administered concurrently with RT have been reported, as clinical research efforts are currently directed to evaluating the effectiveness and safety of cytotoxic and targeted combination chemotherapy regimens administered concurrently with RT.

Sequential Treatment

Sequential therapy, that is, the combination of induction chemotherapy followed by concurrent CRT, represents the most recently developed treatment paradigm in the management of patients with LA SCCHN. It is an attempt to combine the gains observed with both induction chemotherapy (resulting in decreased distant metastases) and concurrent CRT (resulting in improved locoregional control).33,34 It remains unclear at this point if sequential treatment will provide a survival advantage over concurrent CRT; randomized trials addressing this question are currently being conducted.35,36

The most recent attempt at optimizing the induction regimen in a sequential treatment approach has been the TAX 324 study,33 which is a phase III registration trial comparing two induction regimens, TPF (docetaxel, cisplatin, 5-FU) and PF (cisplatin, 5-FU), each followed by concurrent CRT with carboplatin (administered weekly at an area under the concentration-time curve of 1.5). After a median follow-up of 42 months, the TPF arm demonstrated statistically significant improvement in both median PFS (36 vs. 13 months) as well as OS (62% vs. 48%) compared with the PF arm.

However, improved outcomes were achieved at a cost because sequential therapy regimens have been associated with significant acute toxicities. The TPF regimen has been associated with increased incidence of neutropenia and febrile neutropenia despite prophylactic antibiotic use. Interestingly, not all toxicities occurred more frequently in the three-drug combination regimen TPF, as mucositis and treatment delays were more frequent in the two-drug combination regimen PF.

Therefore, selection of the appropriate patients appears to be critical. Sequential therapy protocols should be preferentially offered to younger patients, patients with a good performance status (ECOG performance status 0 or 1), normal end-organ function, and no significant comorbidities. Patients with T4 primary tumors, as well as extensive lymphadenopathy (N2 and N3), may benefit the most from a sequential therapy regimen, as it might control better the risk for metastases.

Further optimization of the chemotherapy regimens used in the sequential treatment protocols will be accomplished once the proper incorporation of molecularly targeted therapies, such as the monoclonal anti-EGFR antibody cetuximab, has been defined. Currently, the addition of cetuximab to cytotoxic regimens both in induction as well as with concurrent chemoradiation appears feasible, but confirmatory results from large clinical trials are still lacking.

MOLECULARLY TARGETED AGENTS IN LA SCCHN

EGFR has been shown to be overexpressed in SCCHN and has been associated with worse prognosis.37,38 Activation of EGFR promotes angiogenesis and proliferation therefore facilitating tumor growth and metastasis.39

It is not surprising therefore that EGFR inhibition in patients with SCCHN has been an early target for drug development. The monoclonal anti-EGFR antibody binds to the receptor and prevents phosphorylation and activation of downstream kinases.

Cetuximab was evaluated in a phase III clinical trial comparing RT alone to RT with cetuximab in patients with LA SCCHN. The addition of cetuximab resulted in statistically significant improvement in both locoregional control (24 vs. 15 months) and rates of PFS (42% vs. 31%) and OS (55% vs. 45%). Overall, cetuximab was well tolerated. Compared with RT alone, cetuximab was associated with rare infusion reactions, hypomagnesemia, and the development of acneiform rash in the majority of exposed patients. Although not observed in the initial trial, subsequent data point to increased rates and severity of radiation dermatitis and mucositis in patients treated with concurrent cetuximab and RT.

It remains unclear how cetuximab compares with cytotoxic radiosensitizing chemotherapy, as direct comparisons have not been reported and current research efforts are focused on how best to combine cytotoxic chemotherapy and cetuximab with concurrent RT, and many clinical trials are currently attempting to optimize combination regimens.

It also remains unclear in which subgroup of patients with LA SCCHN cetuximab should be the radiosensitizing agent of choice. For patients who are not old, with an excellent performance status, no compromise of their end-organ functions, and no significant comorbidities, cisplatin radiosensitizing chemotherapy represents the widely accepted standard of care. For patients who are not eligible for cytotoxic chemotherapy, representing a significant proportion of newly diagnosed LA SCCHN patients, cetuximab should be always considered.

ROLE OF CHEMOTHERAPY IN RECURRENT DISEASE

For patients who develop locally recurrent disease or a second primary within the radiation field, salvage surgery represents the best option for improving survival, if technically feasible.

Administration of induction chemotherapy prior to surgery and re-irradiation has been studied. For example, a small clinical trial using an induction regimen of pemetrexed and gemcitabine and carboplatin and pemetrexed as radiosensitizers reported an encouraging 42% 1-year survival in an early abstract,40 but it is impossible to compare this with other published reports using different approaches because outcomes appear to be primarily driven by patient selection.

For patients not eligible for surgical resection or who deny surgery, palliative chemotherapy still represents the standard of care, but re-irradiation is increasingly being used. In this setting, concurrent administration of chemotherapy as a way to overcome radioresistance is conceptually well justified but has not been optimized. Outside of a clinical trial, administration of a platinum compound either alone or in combination with a taxane of 5-FU is used. Decisions are driven by patient characteristics, including age, performance status, comorbidities, and expected toxicities.41,42 In all re-irradiation clinical research attempts, acute toxicities have been a serious concern, as reported outcomes from phase II clinical trials conducted by RTOG show 8 to 11% treatment-related fatalities.

Given poor outcomes and significant toxicities, novel agents are urgently needed. Unfortunately, most of these trials are single-institution, small phase I/II trials, which are more useful in early identification of potential safety issues rather than evaluation of efficacy given inevitable patient selection bias. Current efforts evaluating various anti-EGFR molecules alone or in combination with anti-angiogenesis agents are under way.

CHEMOTHERAPY IN METASTATIC DISEASE

Overall prognosis of patients diagnosed with metastatic disease is poor, with a median survival of 6 to 9 months. Survival and quality of life vary widely based on patient and disease parameters. The role of systemic palliative chemotherapy versus best supportive care has been studied, and an improved median survival by 2.5 months over best supportive care with the use of a cisplatin-containing regimen was demonstrated.43

Depending on patient's age, performance status, and comorbidities, palliative chemotherapy recommendations may include single-agent or combination cytotoxic chemotherapy or molecularly targeted agents either alone or in combination with cytotoxic chemotherapy.44,45 Numerous chemotherapeutic agents have shown single-agent activity including, but not limited to, cisplatin,46,47 taxanes,48,49 5-FU,50,51 gemcitabine,52,53 pemetrexed,54 etoposide,55 irinotecan,56,57 and methotrexate.58,59

Observed response rates for single-agent cytotoxic chemotherapy range from 15 to 30% with responses lasting 3 to 5 months on average. Molecularly targeted agents show lower response rates, ranging from 10 to 13% for the monoclonal anti-EGFR antibody cetuximab60 to 1 to 11% for the tyrosine kinase inhibitors erlotinib61 and gefitinib.62,63,64,65,66

For patients with excellent performance status, normal end-organ function, and no significant comorbidities, combination chemotherapy regimens are recommended. Most frequently used are two-drug combination regimens (cisplatin + 5-FU,67,68 cisplatin + paclitaxel,69,70 cisplatin + docetaxel,71,72,73,74 carboplatin + taxane75,76,77) and are associated with improved response rates compared with single agent, but they are also associated with increased toxicity and no statistically significant survival benefit.

Cetuximab has a modest single-agent activity, and its addition to cisplatin compared with cisplatin alone has led to an improvement in response rate (26% vs. 10%) but with no improvement in PFS or OS.78 However, the addition of cetuximab to the two cytotoxic drug combination of cisplatin and 5-FU (PF) resulted in a statistically significant improvement in both the PFS (5.6 vs. 3.3 months) as well as the OS (10.1 vs. 7.4 months) when compared with cisplatin and 5-FU alone in a phase III European trial44 and could become a new standard of care for first-line treatment of metastatic SCCHN.

ROLE OF CHEMOTHERAPY IN HUMAN PAPILLOMA VIRUS–ASSOCIATED HEAD AND NECK CANCER

Recent epidemiologic and molecular studies have provided evidence of a causal association between (human papilloma virus) HPV and a subset of head and neck cancers. The overall prevalence of HPV-associated head and neck cancer appears to be around 26%.79,80,81 HPV prevalence is higher in oropharyngeal SCC and lower in oral and laryngeal SCC.82,83

Specific highly oncogenic HPV types are involved; HPV 16 accounts for the majority of cases followed by HPV 18. HPV 16 appears to be responsible for the majority of HPV-positive oropharyngeal SCCs, pointing to specific virus–tissue interactions. Oncogenic HPVs, other than HPV 16 and HPV 18, including HPV 31, 33, and 35, have rarely been associated with SCCHN.

Interestingly, the annual incidence rates of potentially HPV-associated cancers of the tonsil and base of tongue both increased significantly from 1998 through 2003 with an annual percentage change equal to 3.0, whereas the incidence rates of cancer at the comparison sites generally decreased. Incidence rates for these sites were highest among blacks and higher among non-Hispanics and men than among Hispanics and women.84,85

HPV-associated SCCHN tends to have distinct characteristics. Clinically, patients diagnosed with HPV-associated SSCHN demonstrate improved disease-specific survival. Morphologically, HPV-associated SSCHN tends to have a characteristic basaloid morphology and molecularly is less likely to have TP53 mutations.

HPV-associated SCCHN was independently associated with several measures of sexual behavior and exposure to marijuana, but not with tobacco smoking, alcohol drinking, or poor oral hygiene. Associations increased in strength with increasing number of oral sex partners and with increasing intensity (joints per month), duration, and cumulative joint-years of marijuana use. By contrast, non-HPV-associated SCCHN was associated with measures of tobacco smoking, alcohol drinking, and poor oral hygiene but not with any measure of sexual behavior or marijuana use. Associations increased in strength with increasing intensity (cigarettes per day), duration, and cumulative pack-years of tobacco smoking, increasing years of heavy alcohol drinking, and increasing number of lost teeth.86

In conclusion, accumulating evidence confirms that HPV-associated SCCHN comprises a distinct molecular, clinical, and pathologic disease entity that has an improved prognosis. Current treatment algorithms do not take into account HPV tumor status for management recommendations, but clinical trial concepts specific for HPV-positive or HPV-negative SCCHN are currently under development.

ROLE OF CHEMOTHERAPY IN THE MANAGEMENT OF NASOPHARYNGEAL CARCINOMA

Nasopharyngeal carcinoma (NPC) is a unique cancer of the head and neck with distinct epidemiology, pathology, and natural history.

Role of Chemotherapy in the Management of Locally Advanced NPC

The currently employed standard of care regimen for locally advanced NPC is the regimen evaluated in the Intergroup Study 0099, a phase III randomized trial of RT versus concurrent CRT followed by adjuvant chemotherapy, which showed a statistically significant improvement in 5-year survival rates from 37% on the RT-alone arm to 67% in the chemotherapy and radiation arm. The chemotherapy regimen used in this trial included high-dose cisplatin (100 mg/m2) administered on days 1, 22, and 43 of concurrent RT, followed by three cycles of cisplatin and 5-FU (PF) adjuvant chemotherapy.87

Observed clinically and statistically improved outcomes occurred at the cost of increased toxicities. In the Intergroup 0099 study, only 55% of patients in the CRT arm completed all three planned cycles of adjuvant chemotherapy. It still remains unclear if adjuvant chemotherapy after CRT contributes (and to what degree) to improved outcomes. Outcomes remain comparable when trials including adjuvant chemotherapy after CRT are compared with trials with CRT alone.88,89,90,91,92,93 Furthermore, meta-analyses evaluating the role of adjuvant chemotherapy after CRT have not been able to demonstrate improved outcomes such as improved locoregional control, decreased risk of distant metastases, or improved OS with the addition of adjuvant chemotherapy.94,95

However, given the lack of randomized data, recommendations on administration of adjuvant chemotherapy after CRT should be individualized based on the characteristics and preferences of individual patients.

Role of Chemotherapy in the Management of Recurrent NPC

Salvage surgery if technically feasible represents the best option for possible cure but is associated with significant surgical complications including death, deformities, and functional deficits. In the setting of disease that is not surgically resectable, re-irradiation protocols with administration of concurrent chemotherapy represents an effective option if the patient is a re-irradiation candidate. In this setting, a platin and taxane chemotherapeutic combination is frequently used. As is the case in recurrent SCC of other primary sites, re-irradiation protocols in the recurrent NPC setting are associated with significant toxicities, including treatment-related death rates of up to 17%.

Role of Chemotherapy in the Management of Metastatic Disease

Chemotherapy has a palliative role in this setting. Participation in clinical trials is encouraged in cases where the patient's age, performance status, comorbidities, and end-organ function meet eligibility criteria. Palliative chemotherapy regimens evaluating single-agent or combination cytotoxic chemotherapy with or without molecularly targeted agents, addressing anti-EGFR and/or anti-angiogenic strategies, are being evaluated.

CONCLUSION

Over the past two decades, major advances in head and neck oncology have occurred. In this setting of continuously evolving multimodality management algorithms, chemotherapy plays an increasing role in all stages of SCCHN. Further improvements in clinical outcomes are needed, and optimized incorporation of new molecularly targeted agents represents the biggest hope and challenge for head and neck medical oncology.

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