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|Year : 2006 | Volume
| Issue : 2 | Page : 56-64
The role of reirradiation versus chemotherapy in recurrent head and neck cancer
Jenifer Jeba, Reena George
Palliative Care Unit, Christian Medical College, Vellore - 632 004, India
Palliative Care Unit, Christian Medical College, Vellore - 632 004
Source of Support: None, Conflict of Interest: None
Head and neck cancer recurrences after definitive radiotherapy present a difficult therapeutic problem, as only a small proportion of patients have resectable disease. When surgery is not possible, reirradiation might be a feasible option for selected patients, particularly those with favourable prognostic factors such as second primaries, nasopharyngeal or laryngeal tumours or delayed recurrences. Current evidence indicates that in this group of patients reirradiation offers better control rates than palliative chemotherapy. The loco regional control rates of reirradiation without surgery is 20% at five years and 27% at two years. The overall survival rate with reirradiation ranges from 10% to 35% at two years and 0% to 14.6% at five years. The first randomized trial directly comparing chemotherapy with reirradiation is in progress. This article outlines the indications for and results of reirradiation and chemotherapy in post radiotherapy recurrences of head and neck cancer.
Keywords: Chemotherapy, head and neck cancer, larynx, nasopharynx, reirradiation, toxicity
|How to cite this article:|
Jeba J, George R. The role of reirradiation versus chemotherapy in recurrent head and neck cancer. Indian J Palliat Care 2006;12:56-64
| » Introduction|| |
More than 70% of patients with head and neck cancer present with advanced loco-regional disease (stage III and IV). Despite aggressive local therapy fewer than 30% remain disease free at three years. The local or regional failure rates of squamous cell carcinomas of the head and neck range between 20% and 57%.,,,, The cumulative estimated five year incidence of loco regional relapse is 29-31% in high risk patients after surgery and postoperative chemo radiotherapy.,, If left untreated the prognosis of patients with recurrent head and neck cancer is poor, with a median survival of five months. The incidence of second primary neoplasms is between 16-30%.,
The treatment options include surgery, palliative chemotherapy, supportive care or re-irradiation with or without concurrent chemotherapy. Surgery is the optimal therapy, when disease is amenable to complete resection; however, this is feasible only in a small subset of patients.
Currently, the most common treatment for patients with previously irradiated, unresectable disease remains single-agent or multi-agent chemotherapy with response rates between 10% and 40% and median survivals of six to eight months.,,
Administration of a second course of radiation to tissues within a previous radiation portal has been considered unsafe. Physicians are sometimes unaware that reirradiation is feasible in certain cases. Since radiation facilities are available in many parts of India, we wish to outline the role of reirradiation in recurrent head and neck cancer. The earliest clinical studies on re-irradiation, date back to 1959.
Patient selection and prognostic factors
From the limited available evidence patients most likely to benefit are: patients suitable for debulking surgery; patients with second primary cancers as opposed to local recurrences; primary tumours in the nasopharynx and larynx and longer disease free intervals.
[Table - 1],[Table - 2] summarize the results of some studies done on reirradiation alone and reirradiation with surgery respectively. Patients treated with resection and reirradiation [Table - 2] have better local control and survival as compared to those treated with reirradiation alone [Table - 1]. The loco regional control rate of reirradiation without surgery is reported as 20% at five years and 27% at two years, [Table - 1] as compared to 51-81% for reirradiation with surgery at three years [Table - 2]. The overall survival rate with reirradiation ranges between 10-35% at two years and 0-14.6% at five years. [Table - 1] The survival rates are higher in patients who have also had surgery and range from
22-63% at three years and as high as 34.5% at five years [Table - 2]. The high control rate and better overall survival is probably because the recurrence was small and amenable to surgery. Postoperative reirradiation has superior results to salvage surgery alone.
Second primary cancers
Second primary tumours, as opposed to true local regional recurrences, appear to have a better outcome. This may be because a true primary tumor recurrence arises from a group of radiation-resistant clonogens. In the radiation therapy oncology group (RTOG) 96-10 trial the one year survival rate for patients with a second primary was 54% compared with 38% in those with recurrence ( P = 0.083). Stevens et al reported a five-year survival of 37% for patients with new second primary cancers and 17% for patients with recurrent cancers. Loco-regional tumor control was also higher in the patients with new tumours when compared to those with recurrent tumours (60% vs 27%).
Primary site-nasopharynx and larynx
In patients who do have local recurrences, benefit with reirradiation is more likely to be seen when the primary is in the nasopharynx or larynx.,,,
Nasopharyngeal tumours are especially favourable, Wang et al reported five year survival rates of 50% (n=51), with T 1 and T 2 post RT recurrences. Seven patients were alive for more than ten years and three for more than 20 years.
In recurrent nasopharyngeal tumours, three dimensional conformal radiotherapy, intensity modulated radiation therapy and radio surgery boosts have been used with good results.,,,
Laryngeal recurrences also do well with high doses of re-irradiation with five-year local control and survival rates of 60% and 93%, respectively. Ohizumi et al identified nasopharynx, larynx and oropharynx as favourable sites and oral cavity, nasal cavity or hypopharynx as unfavorable sites.
Long disease free interval
In the RTOG 96-10 trial it was found that patients who received their primary radiation three years or more before the repeat radiation had a one-year survival rate of 48% as compared with 35% for patients treated within three years ( P = 0.017). The interval between prior radiation and re-irradiation was however, not a significant prognostic indicator of survival in RTOG 96-11.
| » Reirradiation|| |
There are many studies on Reirradiation and palliative chemotherapy [Table - 1],[Table - 2],[Table - 3] in patients with recurrent head and neck cancer, but there are no randomized trials comparing the two. The first randomized trial comparing re-irradiation and concurrent chemotherapy versus chemotherapy alone for inoperable, previously irradiated, locally recurrent or second primary squamous cell head and neck cancer is underway (RTOG 0421).
The Institut Gustave-Roussy reported one of the largest reirradiation experiences with 169 patients. The two-year survival in patients who received conventional radical radiotherapy with or without chemotherapy was 25%. Overall survival rates were higher in patients with smaller radiotherapy treatment volumes. In two multi institutional studies by the Radiation Therapy Oncology group the two-year survival rates were 16.9% and 24.9%.,
A retrospective study from India reported on 29 patients who received reirradiation along with chemotherapy. The overall response rate was 83% with complete response in 31%. All complete responders had received a cumulative radiotherapy dose of more than 100 Gy. The median survival was nine months and the one and two-year survival rates were 41% and 12%, respectively.
Post operative reirradiation [Table - 2]
Patients with locally recurrent, previously irradiated squamous cell carcinoma of the head and neck, who had poor prognostic findings post surgery (n=130), were randomized to either receive postoperative chemo radiotherapy (60 Gy) or observation. The results showed significant improvement in progression free survival in the postoperative chemo-re-irradiation group ( P= 0.01), but did not provide a statistically significant overall survival advantage.
Kasperts et al prospectively studied 39 patients who received postoperative reirradiation for poor prognostic factors. The three-year overall survival rate was 44% with a loco regional control rate of 74%.
Reirradiation has also been administered using local interstitial brachytherapy for primary and nodal recurrences. Reported local control rates have been 60% to 70% and 5-year overall survivals 60% to 70%.,,
Postoperative high dose rate brachytherapy was administered to 25 patients who underwent salvage surgery for cancers arising in a previously irradiated field. Although 88% of patients had either close or microscopically positive margins, the four-year local control rate and overall survival were 85.6% and 46.4%, respectively.
Radiation dose intensity
Adequate radiotherapy doses are needed for optimal outcomes in radical reirradiation. High doses of reirradiation are necessary in the radical treatment of recurrent tumor, because of the origin of recurrence from radiation resistant clonogens. Various studies have shown higher control rates with higher doses of radiation.,,,
Haraf et al reported a two year survival of 35% in patients who received over 58 Gy as compared to 8% in those who received less than 58 Gy. Langlois et al showed that local control was achieved in 55% of patients who received a dose greater than 60 Gy as compared to 8% for doses less than 60 Gy.
In a recent review, Wong et al have summarized the adverse effects of reirradiation.
The most serious reported toxicity is carotid rupture, which occurs in 1-5% of patients, in the setting of re-irradiation. Carotid rupture results in death in almost all instances, except in the study by Salama et al where one of six patients who had a carotid rupture survived.,, Vascular stenosis and thromboembolism have also been reported.,,,,,
The incidence of Grade 3 and 4 acute mucositis varies between 5-32% in different studies.,,,, De Crevoisier reported osteoradionecrosis in 16% and cervical fibrosis in 40%. Many studies have not comprehensively reported on late toxicity.
Aspects such as quality of life, difficulties with eating, nutrition, speech, pain, fatigue, which are important in weighing the benefit of re-irradiation, have not been addressed in most studies. Data from the University of Chicago show that intelligible speech was preserved in 85%, but only 25% of patients were able to swallow solids without dependence on enteral supplementation.
The frequency of significant hematologic toxicity varies and depends on the chemotherapy regimen used. The combination of hydroxyurea and 5 Fluorouracil (FU) has been found to have only mild to moderate myelosuppressive effects with fewer than 10% of patients developing grade 3 or 4 neutropenia, as compared to regimens such as docetaxel/cisplatin and paclitaxel/cisplatin where grade 3 or worse neutropenia occurs in approximately one third of patients.
| » Chemotherapy|| |
[Table - 3] lists studies on chemotherapy in recurrent head and neck cancer. Unlike in the studies on reirradiation, most studies have not reported two year or five-year survival rates or local control. Wong et al undertook a secondary analysis of two Eastern Cooperative Oncology Groups (ECOG) trials that studied cisplatin, paclitaxel or cisplatin with either 5FU or paclitaxel in patients with recurrent or metastatic cancer. The 2-year survival was 10.5%, which is less than results reported with reirradiation with or without chemotherapy. Most studies have reported response rates that range from 10-35% and median survival ranging from 5 -8.7 months [Table - 3].
Randomized trials on combination chemotherapy, with cisplatin and 5-FU or methotrexate have shown increased response rates but failed to show a survival benefit over single-agent therapy.,,
Two randomized controlled trials have studied the role of taxanes. The combination of cisplatin and paclitaxel was not more effective, in terms of response and survival, than cisplatin and 5-FU. Hematological toxicity was seen in upto 70% of patients despite the use of granulocyte-colony stimulating factor in those receiving high-dose paclitaxel and 78% in those who received low dose paclitaxel.
| » Targeted therapies|| |
Molecular targeted agents, which do not have overlapping toxicities with chemotherapy agents, are being studied for improving response to treatment. The epidermal growth factor receptor (EGFR) is expressed widely and at high levels in squamous cell carcinoma of the head and neck region and is associated with a poor prognosis.
EGFR inhibitors including monoclonal antibodies such as cetuximab and tyrosine kinase inhibitors, such as erlotinib and gefitinib have been used in small trials.,,
| » Conclusion|| |
Recurrent head and neck cancer, within the irradiated field is a difficult and common therapeutic problem. Though surgical resection is the best treatment, only a small subset of patients have resectable disease. In selected patients with borderline operability, the option of debulking followed by postoperative reirradiation can be considered.
When surgery is not possible, reirradiation is a feasible option for some patients. It is important to carefully select patients with favourable prognostic factors, such as second primary tumours, recurrence in the nasopharynx or larynx or delayed recurrences. From the evidence so far, it appears that in this select group of patients reirradiation offers better control rates than palliative chemotherapy. However the results of the RTOG 0421 will provide the first direct comparison between reirradiation and chemotherapy.
An optimal treatment schedule has not yet been defined. Radiation portals must be tight to avoid excessive irradiation of normal tissues. The reirradiation dose should be optimum, ranging from 60 to 70 Gy. Patients must be fully informed of the potential life-threatening toxicities and the impact on quality of life. Future trials should aim to identify those patients with the greatest chance of benefit while optimizing the chemotherapy and radiation schedules.
Attention to pain and symptoms; emotional and body image issues; and questions on nutrition and prognosis are important in these patients just as they are for the large proportion of patients with recurrent head and neck cancer who will either not be suitable for, or have access to salvage therapy.
| » References|| |
|1.||Vokes EE, Weichselbaun RR, Lippman SM, Hong WK. Head and neck cancer. N Engl J Med 1993;328:184-94. |
|2.||Pernot M, Malissard L, Hoffstetter S, Luporsi E, Peiffert D, Aletti P, et al . The study of tumoral, radiobiological and general health factors that influence results and complications in a series of 448 oral tongue carcinomas treated exclusively by irradiation. Int J Radiat Oncol Biol Phys 1994;29:673-9. |
|3.||Calais G, Bardet E, Sire C, Alfonsi M, Bourhis J, Rhein B, et al . Radiotherapy with concomitant weekly docetaxel for stages III/IV oropharynx carcinoma: Results of the 98-02 GORTEC phase II trial. Int J Radiat Oncol Biol Phys 2004;58:161-6. |
|4.||Lefebvre JL, Chevalier D, Luboinski B, Kirkpatrick A, Collette L, Sahmoud T. 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 1996;88:890-9. [PUBMED] [FULLTEXT]|
|5.||Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, et al . Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003;349:2091-8. |
|6.||Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, et al . Latetoxicity results of the GORTEC 94-01 randomized trial comparing radiotherapy with concomitant radiochemotherapy for advanced stage oropharynx carcinoma: Comparison of the LENT/SOMA, RTOG/EORTC and the NCI-CTC scoring sytems. Int J Radiat Oncol Biol Phys 2003;55:93-8. |
|7.||Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al . Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-44. |
|8.||Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, et al . Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945-52. |
|9.||Bernier J, Cooper JS, Pajak TF, van Glabbeke M, Bourhis J, Forastiere A, et al . Defining risk levels in locally advanced head and neck cancers: A comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (#9501). Head Neck 2005;27:843-50. |
|10.||Stell PM. Survival times in end-stage head and neck cancer. Eur J Surg Oncol 1989;15:407-10. [PUBMED] |
|11.||Leon X, Quer M, Diez S, Orus C, Lopez-Pousa A, Burgues J. Second neoplasm in patients with head and neck cancer. Head Neck 1999;21:204-10. [PUBMED] [FULLTEXT]|
|12.||Cooper JS, Pajak TF, Rubin P, Tupchong L, Brady LW, Leibel SA, et al . Second malignancies in patients who have head and neck cancer: Incidence, effect on survival and implications based on the RTOG experience. Int J Radiat Oncol Biol Phys 1989;17:449-56. |
|13.||Jacobs C, Lyman G, Velez-Garcia E, Sridhar KS, Knight W, Hochster H, et al . A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 1992;10:257-63. |
|14.||Forastiere AA, Metch B, Schuller DE, Ensley JF, Hutchins LF, Triozzi P, et al . Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck: A Southwest Oncology Group study. J Clin Oncol 1992;10:1245-51. |
|15.||Williams SD, Velez-Garcia E, Essessee I, et al . Chemotherapy for head and neck cancer. Comparison of cisplatin + vinblastine + bleomycin versus methotrexate. Cancer 1986;57:18-23. |
|16.||Emami B, Bignardi M, Spector GJ, Devineni VR, Hederman MA. Reirradiation of recurrent head and neck cancers. Laryngoscope 1987;97:85-8. |
|17.||Haraf DJ, Weichselbaum RR, Vokes EE. Reirradiation with concomitant chemotherapy of unresectable recurrent head and neck cancer: A potentially curable disease. Ann Oncol 1996;7:913-8. |
|18.||Langendijk JA, Kasperts N, Leemans CR, Doornaert P, Slotman BJ. A phase II study of primary reirradiation in squamous cell carcinoma of head and neck. Radiother Oncol 2006;78:306-12. |
|19.||Janot F, De Rancourt D, Castaing M, et al . Re-irradiation combined with chemotherapy after salvage surgery in head and neck carcinoma: A randomized trial from the GETTEC and GORTEC groups. J Clin Oncol 2006;24:282s. |
|20.||Spencer SA, Harris J, Wheeler RH, Machtay M, Schultz C, Spanos W, et al . RTOG 96-10: Reirradiation with concurrent hydroxyurea and 5-fluorouracil in patients with squamous cell cancer of the head and neck. Int J Radiat Oncol Biol Phys 2001;51:1299-304. |
|21.||Stevens KR Jr, Britsch A, Moss WT. High-dose reirradiation of head and neck cancer with curative intent. Int J Radiat Oncol Biol Phys 1994;29:687-98. |
|22.||Pomp J, Levendag PC, van Putten WL. Reirradiation of recurrent tumour in the head and neck. Am J Clin Oncol 1988;11:543-9. |
|23.||Ohizumi Y, Tamai Y, Imamiya S, Akiba T. Prognostic factors of reirradiation for recurrent head and neck cancer Am J Clin Oncol 2002;25:408-13. |
|24.||Dawson LA, Myers LL, Bradford CR, Chepeha DB, Hogikyan ND, Teknos TN, et al . Conformal re-irradiation of recurrent and new primary head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001;50:377-85. |
|25.||Wang CC. Re-irradiation of recurrent nasopharyngeal carcinoma: Treatment techniques and results. Int J Radiat Oncol Biol Phys 1987;13:953-6. |
|26.||Wu DH, Chen LH. Therapeutic effects of three-dimensional conformal radiation therapy for locally recurrent nasopharyngeal carcinoma Di Yi Jun Yi Da Xue Xue Bao 2002;22:1028-9. |
|27.||Chua DT, Sham JS, Leung LH, Au GK. Re-irradiation of nasopharyngeal carcinoma with intensity-modulated radiotherapy. Radiother Oncol 2005;77:290-4. |
|28.||Lu TX, Mai WY, Teh BS, Zhao C, Han F, Huang Y, et al . Initial experience using intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys.2004;58:682-7. |
|29.||Wang CC, McIntyre J. Re-irradiation of laryngeal carcinoma: Techniques and results. Int J Radiat Oncol Biol Phys 1993;26:783-5. |
|30.||Horwitz EM, Harris J, Langer CJ, et al . Concurrent split course hyperfractionated radiotherapy (Hfx RT), cisplatin (DDP) and paclitaxel (P) in patients with recurrent, previously irradiated squamous cell carcinoma of the head and neck (SCCHN): Update of RTOG 9911. J Clin Oncol 2005;23:519s. |
|31.||De Crevoisier R, Bourhis J, Domenge C, Wibault P, Koscielny S, Lusinchi A, et al . Full-dose reirradiation for unresectable head and neck carcinoma: Experience at the Gustave-Roussy Institut in a series of 169 patients. J Clin Oncol 1998;16:3556-62. |
|32.||Kramer NM, Horwitz EM, Cheng J, Ridge JA, Feigenberg SJ, Cohen RB, et al . Toxicity and outcome analysis of patients with recurrent head and neck cancer treated with hyperfractionated split-course reirradiation and concurrent cisplatin and paclitaxel chemotherapy from two prospective phase I and II studies. Head Neck 2005;27:406-14. |
|33.||Schaefer U, Micke O, Schueller P, Willich N. Recurrent head and neck cancer: Retreatment of previously irradiated areas with combined chemotherapy and radiation therapy: Results of a prospective study. Radiology 2000;216:371-6. |
|34.||Yoodhvir Singh Nagar, Shalini Singh and Niloy Ranjan Datta Chemo-reirradiation in Persistent / Recurrent Head and Neck Cancers. Jpn J Clin Oncol 2004;34:61-68. |
|35.||Salama JK, Vokes EE, Chmura SJ, Milano MT, Kao J, Stenson KM, et al . Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2005;64:382-91. |
|36.||Kasperts N, Slotman BJ, Leemans CR, de Bree R, Doornaert P, Langendijk JA. Results of postoperative reirradiation for recurrent or second primary head and neck carcinoma. Cancer 2006;106:1536-47. |
|37.||Milano MT, Vokes EE, Salama JK, Stenson KM, Kao J, Witt ME, et al . Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel and 5-fluorouracil chemotherapy. Int J Radiat Oncol Biol Phys 2005;61:1096-106. |
|38.||De Crevoisier R, Domenge C, Wibault P, Koscielny S, Lusinchi A, Janot F, et al . Full dose reirradiation combined with chemotherapy after salvage surgery in head and neck carcinoma. Cancer 2001;91:2071-6. |
|39.||Machtay M, Rosenthal DI, Chalian AA, Lustig R, Hershock D, Miller L, et al . Pilot study of post operative reirradiation, chemotherapy and amifostine after surgical salvage for recurrent head and neck cancer. Int J Radiat Oncol Biol Phys 2004;59:72-7. |
|40.||Langlois D, Hoffstetter S, Malissard L, Pernot M, Taghian A. Salvage irradiation of oropharynx and mobile tongue about 192 iridium brachytherapy in Centre Alexis Vautrin. Int J Radiat Oncol Biol Phys 1988;14:849-53. |
|41.||Peiffert D, Pernot M, Malissard L, Aletti P, Hoffstetter S, Kozminski P, et al . Salvage irradiation by brachytherapy of velotonsillar squamous cell carcinoma in a previously irradiated field: Results in 73 cases. Int J Radiat Oncol Biol Phys 1994;29:681-6. |
|42.||Hepel JT, Syed AM, Puthawala A, Sharma A, Frankel P. Salvage high-dose-rate (HDR) brachytherapy for recurrent head-and-neck cancer. Int J Radiat Oncol Biol Phys 2005;62:1444-50. |
|43.||Martinez-Monge R, Alcalde J, Concejo C, Cambeiro M, Garran C. Perioperative high-dose-rate brachytherapy (PHDRB) in previously irradiated head and neck cancer: Initial results of a Phase I/II reirradiation study. Brachytherapy 2006;5:32-40. |
|44.||Wong SJ, Machtay M, Li Y. Locally Recurrent, Previously Irradiated Head and Neck Cancer: Concurrent Re-Irradiation and Chemotherapy or Chemotherapy Alone? J Clin Oncol 2006;24:2653-8. |
|45.||Murros KE, Toole JF. The effect of radiation on carotid arteries: A review article. Arch Neurol 1989;46:449-55. |
|46.||Atkinson JL, Sundt TM Jr, Dale AJ, Cascino TL, Nichols DA. Radiation-associated atheromatous disease of the cervical carotid artery: Report of seven cases and review of the literature. Neurosurgery 1989;24:171-8. |
|47.||Martin JD, Buckley AR, Graeb D, Walman B, Salvian A, Hay JH. Carotid artery stenosis in asymptomatic patients who have received unilateral head-and-neck irradiation. Int J Radiat Oncol Biol Phys 2005;63:1197-205. |
|48.||Dorresteijn LD, Kappelle AC, Scholz NM, Munneke M, Scholma JT, Balm AJ, et al . Increased carotid wall thickening after radiotherapy on the neck. Eur J Cancer 2005;41:1026-30. |
|49.||Dorresteijn LD, Kappelle AC, Boogerd W, Klokman WJ, Balm AJ, Keus RB, et al . Increased risk of ischemic stroke after radiotherapy on the neck in patients younger than 60 years. J Clin Oncol 2002;20:282-8. |
|50.||Hehr T, Classen J, Belka C, Welz S, Schafer J, Koitschev A, et al . Reirradiation alternating with docetaxel and cisplatin in inoperable recurrence of head-and-neck cancer: A prospective phase I/II trial. Int J Radiat Oncol Biol Phys 2005;61:1423-31. |
|51.||Forastiere AA, Leong T, Rowinsky E, Murphy BA, Vlock DR, DeConti RC, et al . Phase III comparison of high-dose paclitaxel + cisplatin + granulocyte colony-stimulating factor versus low-dose Paclitaxel + cisplatin in advanced head and neck cancer: Eastern Cooperative Oncology Group Study E1393. J Clin Oncol 2001;19:1088-95. |
|52.||Gibson MK, Li Y, Murphy B, Hussain MH, DeConti RC, Ensley J, et al . Randomized phase III evaluation of cisplatin plus Fluorouracil versus cisplatin plus paclitaxel in advanced head and neck cancer (E1395): An intergroup trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2005;23:3562-7. |
|53.||Guardiola E, Peyrade F, Chaigneau L, Cupissol D, Tchiknavorian X, Bompas E, et al . Results of a randomized phase II study comparing docetaxel with methotrexate in patients with recurrent head and neck cancer. Eur J Cancer 2004;40:2071-6. |
|54.||Pivot X, Raymond E, Laguerre B, Degardin M, Cals L, Armand JP, et al . Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck. Br J Cancer 2001;85:649-55. |
|55.||Pivot X, Chamorey E, Guardiola E, Magne N, Thyss A, Otto J, et a l. Phase I and pharmacokinetic study of the association of capecitabine-cisplatin in head and neck cancer patients. Ann Oncol 2003;14:1578-86. |
|56.||Airoldi M, Cattel L, Marchionatti S, Recalenda V, Pedani F, Tagini V, et al . Docetaxel and vinorelbine in recurrent head and neck cancer: Pharmacokinetic and clinical results. Am J Clin Oncol 2003;26:378-81. |
|57.||Airoldi M, Cattel L, Cortesina G, Giordano C, Passera R, Pedani F, et al . Gemcitabine and vinorelbine in recurrent head and neck cancer: Pharmacokinetic and clinical results. Anticancer Res 2003;23:2845-52. |
|58.||Espinosa E, Zamora P, Milla A, Morales S, Molina R, Mira M, et al . A phase II trial of cisplatin and vinorelbine in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Head Neck 2002;24:1054-9. |
|59.||Burtness B, Goldwasser MA, Flood W, Matter B, Forastiere AA; Eastern Cooperative Oncology Group. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic / recurrent head and neck cancer: An Eastern Cooperative Oncology Group study. J Clin Oncol 2005;23:8646-54. |
|60.||Soulieres D, Senzer NN, Vokes EE, Hidalgo M, Agarwala SS, Siu LL. Multicenter phase II study of erlotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with recurrent or metastatic squamous cell cancer of the head and neck. J Clin Oncol 2004;22:77-85. |
|61.||Clavel M, Vermorken JB, Cognetti F, et al . Randomized comparison of cisplatin, methotrexate, bleomycin and vincristine (CABO) versus cisplatin and 5-fluorouracil (CF) versus cisplatin (C) in recurrent or metastatic squamous cell carcinoma of the head and neck. A phase III study of the EORTC Head and Neck Cancer Cooperative Group. Ann Oncol 1994;5:521-6. |
|62.||Murphy B, Li Y, Cella D, et al . Phase III study comparing cisplatin (C) and 5-fluorouracil (F) versus cisplatin and paclitaxel (T) in metastatic/ recurrent head and neck cancer (MHNC). Proc Am Soc Clin Oncol 2001;19. |
|63.||Cohen EE, Rosen F, Stadler WM, Recant W, Stenson K, Huo D, et al. Phase II trial of ZD1839 in recurrent or metastatic squamous cell carcinoma of the head and neck. J Clin Oncol 2003;21:1980-7. |
[Table - 1], [Table - 2], [Table - 3]