Haddad R, Tishler RB, Norris CM, Mahadevan A, Busse P, Wirth L, Goguen LA, Sullivan CA, Costello R, Case MA, Posner MR. Docetaxel, cisplatin, 5-fluorouracil (TPF)-based induction chemotherapy for head and neck cancer and the case for sequential, combined-modality treatment.Oncologist. 2003;8(1):35-44.

nccn.org, head and neck

Eckardt A, Wildfang I, Karstens JH.Simultaneous radiochemotherapy with taxol/carboplatin in advanced operable head-neck tumors. Preliminary results. Strahlenther Onkol. 1999 Oct;175 Suppl 3:11-3.

AGARWALA S. S. et al, Long-term outcomes with concurrent carboplatin, paclitaxel and radiation therapy for locally advanced, inoperable head and neck cancer Annals of oncology 2007, vol. 18, no7, pp. 1224-1229

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 2004; 350:1945 – 1952.

Vivek K. Mehta,  Radiotherapy and erlotinibcombined:review of the preclinical and clinical evidence REVIEW ARTICLE published: 10April2012 

Per NCCN on p. FOLL-A, a CT is recommended within 6 months weeks and thereafter imaging is not routinely recommended for symptomatic patients. There are no prospective data demonstrating a survival benefit for any follow-up strategy in patients with treated head and neck cancer and available retrospective data are conflicting.

There are no prospective data demonstrating a survival benefit for any follow-up strategy in patients with treated head and neck cancer and available retrospective data are conflicting. Routine surveillance has been associated with a survival benefit in some observational studies when patients diagnosed at routine follow-up were compared with those who presented with symptoms . However, other studies have not observed a survival benefit from detecting asymptomatic recurrences. This may be because most recurrences are symptomatic early on or because early diagnosis does not appreciably benefit recurrent patients.

Posttreatment surveillance may be most effective in patients who initially have limited disease and who thus retain an option for future curative therapy, such as those with T1 and T2 tumors who received single modality surgery or radiation therapy. Those seem to be the patients who benefit from surveillance in some studies. Despite sureillance survival remains poor for patients who were previously treated for advanced stage disease or who initially presented with regional disease. A this time, there are no guidelines that recommend surveillance for any type of head and neck cancer.

The detection of residual disease after therapy is a particularly difficult problem for patients who have head and neck cancer. Surgery, radiation therapy, and chemotherapy may result in anatomic changes that are difficult to differentiate from recurrent or residual tumor. CT and MRI frequently require serial studies to determine if tumor recurrence is present or absent. FDG-PET is not based on anatomic information, so the functional imaging of PET is able to provide an accurate determination of residual disease after therapy. Several studies have demonstrated the sensitivity of PET in the detection of recurrent or residual disease to be 81% to 100%, and the specificity to be 61% to 100%. The lower specificity results from the false-positive studies that occur with inflammatory lesions after radiation therapy, which may persist for up to 4 months after completion of therapy.

nccn.org, Head and Neck, Oral Cavity, 2012

Francesca De Felice, Daniela Musio, and Vincenzo Tombolini Follow-Up in Head and Neck Cancer: A Management Dilemma Advances in Otolaryngology
Volume 2015 (2015), Article ID 703450.

Ritoe SC, de Vegt F, Scheike IM, et al. Effect of routine follow-up after treatment for laryngeal cancer on life expectancy and mortality: results of a Markov model analysis. Cancer 2007; 10, 9:239.

Francis DO, Yueh B, Weymuller EA Jr, Merati AL. Impact of surveillance on survival after laryngeal cancer in the medicare population. Laryngoscope 2009; 119:2337.

Agrawal A, Hammond TH, Young GS, et al. Factors affecting long-term survival in patients with recurrent head and neck cancer may help define the role of post-treatment surveillance. Laryngoscope 2009; 119:2135.

Manikantan K, Khode S, Dwivedi RC, et al. Making sense of post-treatment surveillance in head and neck cancer: when and what of follow-up. Cancer Treat Rev 2009; 35:744.

Joshi A, Calman F, O’Connell M, et al. Current trends in the follow-up of head and neck cancer patients in the UK. Clin Oncol (R Coll Radiol) 2010; 22:114.

The standard neoadjuvant chemotherapy regimen has consisted of a platinum agent and 5-fluorouracil (5-FU), a regimen known as PF. More recently, the addition of a taxane such as docetaxel (or, less commonly, paclitaxel) to the PF regimen (a triple combination known as TPF) is emerging as a more effective and less toxic standard for induction chemotherapy.

Two large, randomized trials — the Veterans Affairs Laryngeal Cancer Study Group trialand a phase 3 trial conducted by the European Organization for Research and Treatment of Cancer (EORTC) — have demonstrated the benefit of induction chemotherapy with PF (100 mg/m2 of cisplatin on day 1 and 1000 mg/m2 of 5-FU by continuous infusion on days 1-5) with respect to organ preservation. In these trials, overall survival rates were similar in patients receiving either induction PF chemotherapy and radiation or surgery and radiation therapy. In patients with more advanced unresectable tumors, PF induction therapy has been shown to produce long-term survival benefits with overall survival times in a subset of inoperable patients receiving chemotherapy of 21% at 5 years and 16% at 10 years compared with 8% and 6%, respectively, in patients not receiving chemotherapy. In a phase 3 trial[12] of neoadjuvant chemotherapy in patients with oropharyngeal cancer conducted by the French Groupe d’Etude des Tumeurs de la Tete et du Cou (GETTEC), the median overall survival time for patients with both resectable and unresectable tumors was 5.1 years when PF induction chemotherapy was followed by locoregional therapy vs 3.3 years for those who did not receive PF induction chemotherapy (P = .03).

A number of randomized trial have demonstrated improved organ preservation or survival with TPF compared with PF. The phase 3 TAX 323 trial, a direct comparison of PF and TPF induction chemotherapy conducted by the EORTC, included patients with locally advanced and unresectable squamous cell head and neck cancer who were randomized to receive induction therapy with either PF or TPF every 3 weeks for 4 cycles, followed by radiotherapy or surgery.
The international TAX 324 trial assessed PF induction chemotherapy, with or without docetaxel, followed by chemoradiotherapy and surgical resection in patients with locally advanced head and neck cancer. Finally, a randomized phase 3 trial comparing PF induction chemotherapy with and without docetaxel in patients with laryngeal cancer demonstrated an improvement in organ preservation with the addition of the taxane to the PF regimen.

Although the question is still being studied in the DeCIDE trial — Docetaxel Based emotherapy Plus or Minus Induction Chemotherapy to Decrease Events in Head and Neck Cancer — a phase 3 trial sponsored by the University of Chicago, NCCN already lists induction chemotherapy as an option.Two European randomized trials comparing a sequential treatment approach including TPF induction chemotherapy and chemoradiotherapy vs standard chemoradiotherapy alone for the treatment of head and neck cancer are in progress, and data are anticipated within 2 years.

The US Food and Drug Administration (FDA) has approved Taxotere Injection Concentrate combined with cisplatin and 5-fluorouracil for induction therapy of locally advance squamous cell carcinoma of the head and neck before chemoradiotherapy and surgery.

NCCN.ORG, Head and Neck 2012

Salama JK, Haddad RI, Kies MS, Busse PM, Dong L, Brizel DM, Eisbruch A, Tishler RB, Trotti AM, Garden AS.
Clinical practice guidance for radiotherapy planning after induction chemotherapy in locoregionally advanced head-and-neck cancer.Int J Radiat Oncol Biol Phys. 2009 Nov 1;75(3):725-33.

It’s Posner MR, Haddad RI, Wirth L, et al. Induction chemotherapy in locally advanced squamous cell cancer of the head and neck: evolution of the sequential treatment approach. Semin Oncol. 2004;31:778-785.
Remenar E, Van Herpen C, Germa Lluch J, et al. A randomized phase III multicenter trial of neoadjuvant docetaxel plus cisplatin and 5-fluorouracil (TPF) versus neoadjuvant PF in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN). Final analysis of EORTC 24971. Proc Am Soc Clin Oncol. 2006;24:284s. Abstract 5516.
Zorat PL, Paccagnella A, Cavaniglia G, et al. Randomized phase III trial of neoadjuvant chemotherapy in head and neck cancer: 10-year follow-up. J Natl Cancer Inst. 2004;96:1714-1717.
Posner MR, Haddad RI, Wirth LJ. The evolution of induction chemotherapy and sequential therapy for locally advanced squamous cell cancer of the head and neck. American Society of Clinical Oncology Educational Book, 2006; pp 346-352.
Calais G, Pointreau Y, Alfonsi M, et al. Randomized phase III trial comparing induction chemotherapy using cisplatin (P) fluorouracil (F) with or without docetaxel (T) for organ preservation in hypopharynx and larynx cancer. Preliminary results of GORTEC 2000-01. Proc Am Soc Clin Oncol. 2006;24:281s.

Mamoru Miyaguchia1 Lymph node and distant metastases in patients with sinonasal carcinoma
The Journal of Laryngology & Otology (1995), 109:304-307

Eric R. Schmidt, Ronald L. Berry Diagnosis and Treatment of Sinonasal Undifferentiated Carcinoma: Report of a Case and Review of the Literature
Journal of Oral and Maxillofacial Surgery, Volume 66, Issue 7, July 2008, Pages 1505-1510

Transplantation Proceedings, Volume 40, Issue 10, December 2008, Pages 3821-3822
P. De Simone, L. Coletti, D. Campani, A. Falcone, F. Filipponi Liver Transplantation for Metastatic Sinonasal Undifferentiated Carcinoma: A Case Report

Brian S. Kim et al, Sinonasal Malignancies of Neuroendocrine Origin
Hematology/Oncology Clinics of North America, Volume 22, Issue 6, December 2008, Pages 1297-1316

Bevacizumab is an anti-VEGF monoclonal antibody that is FDA-approved for use in other malignancies. Savvides and colleagues from Case Comprehensive Cancer Center in Cleveland reported the preliminary results of a phase 2 study examining the efficacy of bevacizumab in combination with docetaxel and radiation in locally advanced HNC. Eight patients with stage IV disease completed therapy and 5 of 8 had a posttreatment neck dissection that demonstrated a pathologic complete response. These patients are now receiving adjuvant bevacizumab. The addition of this agent to curative CRT appears to be feasible. No episodes of severe bleeding were noted, which has been a concern with this agent. Khuntia and colleagues from the University of Wisconsin presented the design of an ongoing phase 1 trial of neoadjuvant bevacizumab followed by concurrent radiation, cisplatin, and bevacizumab for locally advanced HNC. Results of this study were not yet available.Seiwert and colleagues reported the results of a phase 1 study of bevacizumab plus 5-FU and hydroxyurea with concomitant radiotherapy for poor-prognosis HNC. Thirty-four patients completed treatment and, although there were toxicities, the addition of bevacizumab did not appear to be associated with a major synergistic toxic effect.

Speight PM, Barrett AW: Salivary gland tumours. Oral Dis 8 (5): 229-40, 2002.

Seiwert TY, Haraf DJ, Cohen EE, et al. A phase I study of bevacizumab with fluorouracil and hydroxyurea with concomitant radiotherapy for poor prognosis head and neck cancer. Proc Am Soc Clin Oncol. 2006;24:287s. Abstract 5530.

nccn.org, salvary gland

Savvides P, Greskovich J, Bokar J, et al. Phase II study of bevacizumab in combination with docetaxel and radiation in locally advanced squamous cell cancer of the head and neck (SCCHN). Program and abstracts of the 2007 Multidisciplinary Head and Neck Cancer Symposium; January 18-20, 2007; Rancho Mirage, California. Abstract 122.

Khuntia D, Jeraj R, Kruser TJ, et al. Phase I trial of neoadjuvant bevacizumab followed by concurrent radiation, cisplatin and bevacizumab for locoregionally advanced squamous cell carcinoma of the head and neck. Program and abstracts of the 2007 Multidisciplinary Head and Neck Cancer Symposium; January 18-20, 2007; Rancho Mirage, California. Abstract 63.

Following the observation that the combination of cisplatin plus cetuximab was safe, different clinical trials were performed to test this approach. In a phase III study in metastatic or recurrent SCCHN, 117 patients were randomised to receive cisplatin plus cetuximab, or cisplatin plus placebo. Median PFS was 2.7 months for the control arm and 4.2 months for the experimental arm. Median overall survival was 8.0 months and 9.2 months, respectively. Objective response rates were 10% and 26%. The toxicity was similar in both groups, except for the cutaneous rash associated with cetuximab. Recently, a retrospective evaluation of these clinical trials has been reported. In the study, a total of 330 platinum-refractory patients with recurrent or metastasic SCCHN treated with cetuximab alone or in combination with platinum-based chemotherapy were considered and compared with a historical series of 151 patients. The observed toxicity was mainly cutaneous (69% with the monotherapy treatment and 72% with the combination). The median survival time of around 6 months achieved with cetuximab in platinum-refractory SCCHN is similar to that seen with first-line therapy and represents an increase in survival of 2.5 months compared with platinum-refractory historical controls.

One interpetation of these results is that Erbitux restores platinum sensitivity.

Taking all these data into consideration, the administration of cetuximab in combination with a platinum compound in recurrent or metastatic platinum-resistant SCCHN could be an appropriate therapeutic approach that increases response rate and possibly time to treatment progression, without increased toxicity

In regard to Taxol/platin + cetuximab: A phase II trial evaluating this induction chemotherapy plus cetuximab (Erbitux) resulted in a 100% overall response rate among patients with head and neck cancer. These results were presented at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO).The trial known as Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer (EXTREME), involved 442 patients. About a third had cancer in the oral cavity or hypopharynx, nearly half had metastases, and most patients had already received treatment with radiotherapy (77% – 80%) and chemotherapy (36% – 41%). In this trial, all patients were treated with a chemotherapy regimen containing either carboplatin (in about a third of patients) or cisplatin plus 5-fluorouracil, and 1 group of patients also received cetuximab (400 mg/m² as an initial dose, followed by 250 mg/m² weekly).

I did not find any currently ongoing trials of this combination with either Taxol or Taxotere (except with radiation in stage III) but the consensus of experts is that these results must be confirmed before accepted as standard of care. Per most plan definitions, this renders this combination experimental.  NCCN(CHEM-A) does not list this three drug combination for metastatic disease.  It does list cisplatin and docetaxel and cisplatin/cetuximab.

 L. Licitra, P. Bossi, L. D. Locati, and C. Bergamini
Is Restoring Platinum Sensitivity the Best Goal for Cetuximab in Recurrent/Metastatic Nasopharyngeal Cancer?
J. Clin. Oncol., October 20, 2005; 23(30): 7757 – 7758.

JJ Cruz, A Ocaña, E Del Barco and A Pandiella Targeting receptor tyrosine kinases and their signal transduction routes in head and neck cancer
Annals of Oncology 2007 18(3):421-430;

nccn.org, head and neck

Vermorken J, Bourhis J, Trigo M, et al. (2005) Cetuximab (Erbitux®) in recurrent/metastatic (R&M) squamous cell carcinoma of the head and neck (SCCHN) refractory to first-line platinum-based therapies. Proc Am Assoc Clin Oncol 501s: (Abstr 5505).

Kies M, Garden A, Holsinger C, et al. Induction Chemotherapy (CT) with Weekly Paclitaxel, Carboplatin, and Cetuximab for Squamous Cell Carcinoma of the Head and Neck (HN). Proceedings from the 42nd annual meeting of the American Society of Clinical Oncology. Atlanta, Ga. June 2006. Abstract # 5520.

Chemoresistance assays are a modification that tests resistance to chemo rather than sensitivity. They work on the assumption that if celss show reesistance to very high concentrations of a drug in vitro, they will also be resistant in vivo to that drug.

Going back years, the article by Schrag et al criticized the field of chemosensitivity and chemo resistance(SRA), concluding that these types of in vitro assays are not yet ready for prime time. The panel of authors attempted to present evidence that in vitro drug response assays should not be used clinically. This issue was first addressed by an exhaustive Medicare Coverage Advisory Committee (MCAC) in 1999. A panel of physicians selected by the Department of Health and Human Services reviewed hundreds of articles from the literature and heard two days of testimony by experts in the field in an open hearing. The panel voted unanimously that although chemosensitivity assays should not be covered, drug resistance assays should be paid for. This became a cause celebre with a vigorous debate in the literature and variant opinions offered by professional bodies. The American Society of Clinical Oncology vigorously objected and recommended: ”
The use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting. Oncologists should make chemotherapy treatment recommendations on the basis of published reports of clinical trials and a patient’s health status and treatment preferences. Because the in vitro analytic strategy has potential importance, participation in clinical trials evaluating these technologies remains a priority.”  I believe that the So. California branch of ASCO dissented from this recommendation, see http://weisenthal.org/medicareletter.pdf.

The Extreme Drug Resistance Assay (EDR) Assay is a laboratory test performed on a patient’s tumor cells. This lab test is claimed to determine the probability of a tumor’s resistance to a specific chemotherapy drug. If the tumor cells grow in the presence of very high concentrations of chemotherapy drug, then the cancer cells are considered resistant to that drug.

Drug sensitivity and resistance assays have been examined for their potential utility in ovarian cancer by a number of clinical investigators. Unfortunately, analysis of these studies has suffered greatly from the absence of an appropriate control population. The majority of these trials have compared the survival of individuals whose treatment was selected by a particular assay with a historical/retrospective patient group treated at the same institution. A report in the Gynecologic Cancer session described an important attempt by investigators in Europe to directly address the value of the adenosine triphosphate (ATP)-based tumor chemosensitivity assay, by randomizing patients with platinum-resistant ovarian cancer (n = 180) to either “assay-directed therapy” or the treatment of the “physician’s choice”. The objective response rate was 40.5% for the assay-directed group vs 31.5% for the physician’s choice of treatment. Progression-free survival (intention-to-treat analysis) was 104 days in the assay-directed vs 93 days in the physician’s choice groups. In addition, there was no difference in overall survival between the strategies. This study provides support for the conclusion that the ATP-based tumor chemosensitivity assay is not superior to physician’s choice in the selection of chemotherapy in women with platinum-resistant ovarian cancer.Some experts claim that resistance assays are different from chemosensitivity assays and Medicare does cover them. However, this distinction has not been sufficiently demonstrated and most experts vigorously dispute this.

In conclusion, the technologies and the questions that they raise are quite different. It Oncotech Sensitivy testing not yet been  recommended by professional societies and gudielines pending completion of a phase III trial. With Oncotech ER the situation is more uncertain, NCCN says that “current evidence is not sufficient to supplant standard of care chemotherapy”.

More recently in ASCO 2008, researchers affiliated with Precision Therapeutics and Columbia University reported that a test of chemoresponsiveness (ChemoFX®) can predict survival of patients with advanced ovarian cancer. This remains something that must be confirmed by future studies. NCCN says that “chemosensitivity.resistance assays are being used in some NCCN centers”, which I consider something less than an endorsement. This is a level 3 recommendations, which is defined as: “The recommendation is based on any level of evidence but reflects major disagreement.”

Burstein et al (2011) updated the ASCO Technology Assessment guidelines on CSRAs published in 2004.  An Update Working Group reviewed data published between December 1, 2003, and May 31, 2010.  Medline and the Cochrane Library were searched yielding 11,313 new articles.  The limits for “human and English” were used, and then standard ASCO search strings for randomized controlled trials (RCTs), meta-analyses, guidelines, and reviews were added, yielding 1,298 articles for abstract review.  Of these, only 21 articles met pre-defined inclusion criteria and underwent full text review, and 5 reports of RCTs were included for data extraction.  Review of the literature does not identify any CSRAs for which the evidence base is sufficient to support use in oncology practice.  The authors concluded that the use of CSRAs to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting.  They noted that oncologists should make chemotherapy treatment recommendations based on published reports of clinical trials and a patient’s health status and treatment preferences.  Because the in vitro analytic strategy has potential importance, participation in clinical trials evaluating these technologies remains a priority.

Schrag D, Garewal HS, Burstein HJ, et al: American Society of Clinical Oncology technology assessment: Chemotherapy sensitivity and resistance assays. J Clin Oncol 22 : 3631 -3638, 2004

John P. Fruehauf In Vitro Drug Resistance Versus Chemosensitivity: Two Sides of Different Coins Journal of Clinical Oncology, Vol 23, No 15 (May 20), 2005: pp. 3641-3643

P. Hwu, A. Y. Bedikian, and E. A. Grimm
Challenges of chemosensitivity testing.
Clin. Cancer Res., September 15, 2006; 12(18): 5258 – 5259.

Cree IA. Chemosensitivity and chemoresistance testing in ovarian cancer. Curr Opin Obstet Gynecol. 2009;21(1):39-43.

C.Rass K, Hassel JC. Chemotherapeutics, chemoresistance and the management of melanoma. G Ital Dermatol Venereol. 2009;144(1):61-78.

Lyons JM 3rd, Abergel J, Thomson JL, et al. In vitro chemoresistance testing in well-differentiated carcinoid tumors. Ann Surg Oncol. 2009;16(3):649-655.

National Comprehensive Cancer Network (NCCN). Ovarian cancer including fallopian tube cancer and primary peritoneal cancer. NCCN Clinical Practice Guidelines in Oncology v.2.2011. Fort Washington, PA: NCCN; 2011.

Burstein HJ, Mangu PB, Somerfield MR, et al. American society of clinical oncology clinical practice guideline update on the use of chemotherapy sensitivity and resistance assays. J Clin Oncol. 2011;29(24):3328-3330.

The best quality data in head and neck cancer for locally advanced disease are available for cetuximab since the 2006 publication of a randomized clinical trial comparing radiation treatment plus cetuximab versus radiation treatment alone. This study found that concurrent cetuximab and radiotherapy improves survival and locoregional disease control compared to radiotherapy alone, without a substantial increase in side effects, as would be expected with the concurrent chemoradiotherapy, which is the current gold standard treatment for advanced head and neck cancer. NCCN on p. CHEM-A, recommends cetuximab with radiation as an option.

Bonner J, Harari P, Giralt J, Azarnia N, Shin D, Cohen R, Jones C, Sur R, Raben D, Jassem J, Ove R, Kies M, Baselga J, Youssoufian H, Amellal N, Rowinsky E, Ang K (2006). “Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck”. N Engl J Med 354 (6): 567-78. 2006

Pfister DG, Su YB, Kraus DH, Wolden SL, Lis E, Aliff TB, Zahalsky AJ, Lake S, Needle MN, Shaha AR, Shah JP, Zelefsky MJ.Concurrent cetuximab, cisplatin, and concomitant boost radiotherapy for locoregionally advanced, squamous cell head and neck cancer: a pilot phase II study of a new combined-modality paradigm.J Clin Oncol. 2006 Mar 1;24(7):1072-8.

nccn.org, Head and Neck, 2013

Erbitux, Prescribing INformation, 2013

Conley, Barbara A.
Treatment of Advanced Head and Neck Cancer: What Lessons Have We Learned?
J Clin Oncol 2006 24: 1023-1025

A combined modality approach with chemotherapy and radiation has become standard treatment for nasopharyngeal carcinoma. The most notable prospective trial to date examined induction with 5-FU and cisplatin followed by radiation. Since the introduction of effective chemotherapy as part of the salvage treatment after relapse in these patients with nasopharyngeal cancer, the 5-year survival rate in patients with stage IV disease who received radiation therapy as their initial treatment has risen to the 40% range.

Capecitabine has been studies in a number of phase II studies, especially Chinese studies, yielding response rates of 20-30+%. One study claimed 48% response. Overall, the studies suggest that it is a moderately effective treatment and supported by several phase II trials. A phase I trial has been completed with radiation: Phase I Trial of Induction Paraplatin® and Xeloda® Followed by Concurrent Paraplatin and Xeloda With Intensity Modulated Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Al-Sarraf M, Reddy MS. Nasopharyngeal carcinoma. Curr Treat Options Oncol. 2002;3:21-32.

Mould RF,Tai TH. Nasopharyngeal carcinoma: treatments and outcomes in the 20th century. Br J Radiol. 2002;75:307-339.

Ciuleanu E, Irimie A, Ciuleanu TE, Popita V, Todor N, Ghilezan N.
Capecitabine as salvage treatment in relapsed nasopharyngeal carcinoma: a phase II study.
J BUON. 2008 Jan-Mar;13(1):37-42.

Chua D, Wei WI, Sham JS, Au GK.
Capecitabine monotherapy for recurrent and metastatic nasopharyngeal cancer.Jpn J Clin Oncol. 2008 Apr;38(4):244-9.

Chua DT, Sham JS, Au GK. A phase II study of capecitabine in patients with recurrent and metastatic nasopharyngeal carcinoma pretreated with platinum-based chemotherapy.Oral Oncol. 2003 Jun;39(4):361-6.