Stage IV Hypopharyngeal Cancer
Resectable Hypopharyngeal Cancer
Unresectable Hypopharyngeal Cancer
Current Clinical Trials
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Resectable Hypopharyngeal Cancer
The management of patients with resectable hypopharyngeal cancer is complex and requires
multidisciplinary input to establish the optimal treatment regimen. New
surgical techniques and reconstructions using the gastric pull-up operation or
free jejunal transfers have greatly reduced the morbidity associated with
resection of these tumors and have almost eliminated the need for multistage
reconstructions. This has greatly aided the combined treatment regimens
because these patients have a high likelihood of beginning postoperative
radiation therapy within 3 to 4 weeks following resection.
Details of surgical procedures and their modifications of radiation fields or
dosage schedules are not specifically designated here because of
legitimate variations in techniques that, according to various retrospective
data, give similar survival results in different treatment centers. This group
of patients should be managed by surgeons and radiation oncologists who are
skilled in the multiple procedures and techniques available, and who are
actively and frequently involved in the care of these patients.
Standard treatment options:
- The combination of surgery and radiation, most often postoperative as seen in a follow-up study of preoperative versus postoperative radiation therapy (RTOG-7303), has
become the usual form of therapy for this group of patients in the United
States.[1,2]
- Neoadjuvant chemotherapy as given in clinical trials has been used to shrink
tumors and render them more definitively treatable with either surgery
or radiation. Chemotherapy is given prior to the other modalities, hence the
designation, neoadjuvant, to distinguish it from standard adjuvant therapy, which
is given after or during definitive therapy with radiation or after surgery.
Many drug combinations have been used in neoadjuvant chemotherapy. Neoadjuvant chemotherapy is commonly used to treat patients presenting with
advanced disease to improve locoregional control or survival, despite the
lack of data from randomized, prospective trials.[3] The use of neoadjuvant chemotherapy to increase organ
preservation has also been advocated. In a prospective randomized trial (NCT-00169247), the
European Organization for the Research and Treatment of Cancer has compared surgery plus postoperative radiation therapy to induction
chemotherapy (i.e., cisplatin plus 5-fluorouracil [5-FU]) followed by radiation in responding
patients.[4] Local and regional failures were similar in both groups. Although
median survival was 25 months in the immediate surgery arm of the study and 44
months in the induction chemotherapy arm (P = .006), 5-year disease-free and
overall survival were the same. A functional larynx was preserved in 42% of
patients at 3 years and 35% at 5 years in patients who received induction
chemotherapy.[4][Level of evidence: 1iiA, 1iiC] In contrast to this, another randomized prospective
trial has demonstrated a statistically significant survival advantage for patients
undergoing chemotherapy (i.e., cisplatin plus 5-FU) followed by laryngopharyngectomy
and postoperative radiation therapy when compared with chemotherapy and radiation
therapy.[5][Level of evidence: 1iiA,1iiC] Although organ preservation was not
discussed, chemotherapy in combination with radiation therapy without surgery
should not be considered standard.
- Patients with stage IV hypopharyngeal cancer should be considered for treatment with combined postoperative, adjuvant radiation therapy and chemotherapy. In a prospective randomized trial, postoperative, adjuvant radiation therapy alone was compared to postoperative, adjuvant radiation therapy plus concurrent chemotherapy. Both the overall survival (P <.01) and the disease-free survival (P <.02) were better in the group of patients receiving radiation therapy plus concurrent chemotherapy.[6][Level of evidence: 1iiA] In another study, primary site preservation was improved, though overall survival was not improved when chemotherapy was administered concomitantly with radiation therapy.[7,8]
Unresectable Hypopharyngeal Cancer
Standard treatment options:
- These patients are candidates for radiation therapy.
- Chemotherapy has been combined with radiation therapy in patients who have
locally advanced disease.[9-11] In a randomized trial, the 3-year projected overall survival for patients with stage III or stage IV inoperable disease receiving single daily fractionated radiation with concurrent cisplatin was 37% (P = .14).[11][Level of evidence:1iiA]
Treatment options under clinical evaluation:
- Radiation therapy clinical trials evaluating hyperfractionation schedules
should be considered with chemotherapy.[12-17]
A meta-analysis of 63 randomized prospective trials published between 1965 and
1993 showed an 8% absolute survival advantage in the subset of patients
receiving concomitant chemotherapy and radiation therapy.[18][Level of
evidence: 2A] Patients receiving adjuvant or neoadjuvant chemotherapy had no
survival advantage. Cost, quality of life, and morbidity data were
not available; no standard regimen existed; and the trials were
too heterogenous to provide definitive recommendations. The results of ongoing
trials may further clarify the role of concomitant chemotherapy and radiation
therapy in the management of hypopharyngeal cancer.
The best chemotherapy to use and the appropriate way to integrate the two
modalities is still unresolved.[19]
Posttreatment follow-up:
- These patients should have a careful head and neck examination, looking for
recurrence monthly for the first posttreatment year, every 2 months for the
second year, every 3 months the third year, and every 6 months thereafter.
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV hypopharyngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
References
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Arriagada R, Eschwege F, Cachin Y, et al.: The value of combining radiotherapy with surgery in the treatment of hypopharyngeal and laryngeal cancers. Cancer 51 (10): 1819-25, 1983.
[PUBMED Abstract]
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Tupchong L, Scott CB, Blitzer PH, et al.: Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. Int J Radiat Oncol Biol Phys 20 (1): 21-8, 1991.
[PUBMED Abstract]
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Harari PM: Why has induction chemotherapy for advanced head and neck cancer become a United States community standard of practice? J Clin Oncol 15 (5): 2050-5, 1997.
[PUBMED Abstract]
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Lefebvre JL, Chevalier D, Luboinski B, et al.: Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 88 (13): 890-9, 1996.
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Beauvillain C, Mahé M, Bourdin S, et al.: Final results of a randomized trial comparing chemotherapy plus radiotherapy with chemotherapy plus surgery plus radiotherapy in locally advanced resectable hypopharyngeal carcinomas. Laryngoscope 107 (5): 648-53, 1997.
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Bachaud JM, Cohen-Jonathan E, Alzieu C, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced head and neck carcinoma: final report of a randomized trial. Int J Radiat Oncol Biol Phys 36 (5): 999-1004, 1996.
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Adelstein DJ, Lavertu P, Saxton JP, et al.: Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 88 (4): 876-83, 2000.
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Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004.
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Al-Sarraf M, Pajak TF, Marcial VA, et al.: Concurrent radiotherapy and chemotherapy with cisplatin in inoperable squamous cell carcinoma of the head and neck. An RTOG Study. Cancer 59 (2): 259-65, 1987.
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Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.
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Adelstein DJ, Li Y, Adams GL, et al.: 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 21 (1): 92-8, 2003.
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Weissler MC, Melin S, Sailer SL, et al.: Simultaneous chemoradiation in the treatment of advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 118 (8): 806-10, 1992.
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Jeremic B, Shibamoto Y, Milicic B, et al.: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18 (7): 1458-64, 2000.
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Staar S, Rudat V, Stuetzer H, et al.: Intensified hyperfractionated accelerated radiotherapy limits the additional benefit of simultaneous chemotherapy--results of a multicentric randomized German trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 50 (5): 1161-71, 2001.
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Wendt TG, Grabenbauer GG, Rödel CM, et al.: Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. J Clin Oncol 16 (4): 1318-24, 1998.
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Brizel DM, Albers ME, Fisher SR, et al.: Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 338 (25): 1798-804, 1998.
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Semrau R, Mueller RP, Stuetzer H, et al.: Efficacy of intensified hyperfractionated and accelerated radiotherapy and concurrent chemotherapy with carboplatin and 5-fluorouracil: updated results of a randomized multicentric trial in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 64 (5): 1308-16, 2006.
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Pignon JP, Bourhis J, Domenge C, 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 355 (9208): 949-55, 2000.
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Taylor SG 4th, Murthy AK, Vannetzel JM, et al.: Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer. J Clin Oncol 12 (2): 385-95, 1994.
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