World Journal of Psycho-Social Oncology Volume No 5

Original Article Open Access

Results of an open labeled prospective single group study of quality of life in patients with head neck cancer treated with paclitaxel based chemotherapy

1,4Senniappan Karthikeyan, 1Tushar Goyal, 1,5Umakant Gaud, 2Mridula Shukla, 3Satyajit Pradhan, 1Seema Singh, 1Manoj Pandey.

  • 1Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
  • 2Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
  • 3Department of Radiotherapy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
  • 4Presently working as Assistant Professor, Surgical Oncology, WIA Cancer Institute, Adyar, Chennai, India.
  • 5Presently working as Consultant, Regional Cancer Centre, Hyderabad, India.
  • Submitted: January 19, 2012,
  • Accepted February 10, 2012;
  • Published: February 13, 2012

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective :

The present study was carried out to evaluate the role and response to neoadjuvant chemotherapy in patients with locally advanced head neck cancers and to evaluate its effect on quality of life.

Study Design :

Open labeled single group prospective study

Patients and methods:

A total of 34 patients receiving paclitaxel and platinum based neoadjuvant chemotherapy were recruited in this prospective study. Chemotherapy response was evaluated by RESIST criteria and toxicity was measured by WHO toxicity criteria. Quality of life was measured by FACT-HN questionnaire. Statistical analysis was done by using paired t test.

Results :

Of the 34 patients, 16 had stage III disease while rest had IVA disease. Complete response was seen in 2 patients, while rest had a partial response. Both the patients showing complete response have received paclitaxel with cisplatin. Most of the patients’ had grade I or II gastrointestinal toxicity, no hematological or bone marrow toxicity was seen in any case. A statistically significant improvement in quality of life was seen at the end of three cycles, this improvement was more in patients receiving paclitaxel with cisplatin compared to carboplatin. Trial outcome index also showed significant improvement.


The results of the present study show good response to neoadjuvant chemotherapy with acceptable toxicity and improvements in quality of life. Its long term effect on survival and pattern of failure needs further studies.


Management of locally advanced head and neck (Stage III, IV) squamous cell carcinoma is challenging despite advances in the field of radiotherapy, chemotherapy and Surgery. Historically, primary surgery and/or radiotherapy used to be the treatment of choice for these loco-regionally advanced head neck squamous cell carcinoma (HNSCC) that constitute about 60% of newly diagnosed HNSCC. High rates of loco regional recurrence (50-60%) within 2 years and high distant failure rates (20-30%) have led to the evaluation of new approaches for managing these patents [1,2]. The various effective approaches followed worldwide for the management of locally advanced HNSCC include primary surgery followed by adjuvant radiotherapy or concurrent chemo radiation (CRT); induction chemotherapy (addition of chemotherapy prior to surgery and/or radiotherapy; and sequential therapy (induction chemotherapy followed by concurrent chemo radiation).

Many randomized trials have proved that the addition of chemotherapy to the combined modality approaches in locally advanced HNSCC involving surgery and/or radiotherapy improves clinical outcomes in terms of organ preservation [3-5], better loco-regional control [6], fewer distant failures [5-7] longer time to disease progression and longer overall survival times [7].

The meta-analysis of chemotherapy on Head and Neck cancer (MACH-NC) [8] which analyzed more than 10,000 patients of 63 trials, has demonstrated that addition of chemotherapy to RT in both definite (CRT) and adjuvant postoperative (surgery + CRT) settings resulted in a 12% reduction in the risk of death, with an absolute improvement of 8% on 5-year survival for CRT while that of neoadjuvant chemotherapy was only 2%. Thus most institutions follow the protocol of CRT as the first modality of choice in treatment of locally advanced HNSCC [8-12].

With CRT coming into common practice, the rates of loco-regional disease control were impressive but systemic failures were not controlled. This fact suggested that the intensive CRT regimen though effective in loco-regional activity, may not be effective in controlling the systemic micro metastatic disease. Thus, came the interest in evaluating the role of neoadjuvant chemotherapy before loco-regional treatment.

Numerous chemotherapeutic agents have been tested and it has been widely accepted that cisplatin and 5-FU (PF) regimen is the standard treatment for locally advanced HNSCC patients receiving induction chemotherapy [13-14]. Later studies emphasized the advantages of adding taxanes to PF regimen [15-20].

In the present study, we evaluated patients with locally advanced HNSCC for their responses to the induction chemotherapy regimen of paclitaxel and cisplatin/carboplatin, the effect of the same on, the extent of surgery needed, quality of life and toxicity profile.

Patients and methods Study sample

Thirty four patients with histologically proven head and cancers receiving paclitaxel and platinum based neoadjuvant chemotherapy between July 2006 and March 2008 were evaluated in an open labeled single group prospective study. Following history taking, a detailed examination was carried out that recorded the site, size and number of lesions, Karnofsky performance status, cTNM staging and grade of tumors (Table 1). Patients with synchronous multiple primaries and those with prior treatment were excluded. The study was approved by the Institute Ethics committee and informed written consent was obtained from all patients.

Chemotherapy regimen and dose

All patients received a combination of 3 weekly paclitaxel (175 mg/m2) with either carboplatin (AUC 5) or cisplatin (60mg/m2) in infusion after hydration.

Measurement of response

Response to chemotherapy was evaluated as per the RECIST Criteria. Change in size of the tumor was recorded by a pre treatment and post treatment CT scan. Patients having < 50% response were classified as no response (NR), while > 50% response was considered as partial response (PR). Complete clinical and radiological remission was taken as complete response (CR). Based on the response of patients, patients were selected for further treatment. All patients with complete response were planned for radical external beam radiotherapy while NR and PR group were planned for surgical excision followed by radical radiotherapy or radiotherapy alone depending upon the location and size of the residual primary.

Measurement of Quality of life and toxicity

The assessment of functional outcome and quality of life after induction chemotherapy was done using the Hindi version of the FACT-HN questionnaire (Functional Assessment of Cancer Therapy instrument for Head and Neck cancer questionnaire) which consists of 27 general questions divided into domains for physical well being, social / family well being, emotional well being, and functional wellbeing and 12 disease specific questions related to head and neck cancer.

Table:1: Demographic profile
Site n %
Oral cavity 20 58.8
Oropharynx 4 11.8
Maxilla 6 17.6
Larynx 4 11.8
III 16 47.1
IV A 18 52.9
Presenting features
Ulcer 22 64.7
Dysphagia 12 35.3
Bleeding 8 23.5
Dysarthria 10 29.4
Dyspnea 2 5.9
Change in voice 6 17.6
Trismus 8 23.5
Tumor Grade
Well Differentiated 14 41.2
Moderately Differentiated 6 17.6
Not Otherwise Specified 14 41.2
T Stage
T3 14 41.2
T4 20 58.8
N Stage
No 12 35.3
N1 20 58.8
N2a 2 5.9
Karnofsky status
90% 32 94.1
80% 2 5.9

The toxicity of chemotherapy was evaluated by WHO toxicity criteria. All data were recorded on a preset proforma and was transferred to excel data base. QOL in patients receiving cisplatin with paclitaxel was compared with those receiving combination with carboplatin.

Statistical analysis

At the beginning and end of each cycle the patients were evaluated by a complete hemogram, biochemical investigations for renal function and liver functions. Statistical analysis was carried out using paired ‘t’ test for continuous variables and quality of life scores.


Patient demography

A total of 30 male and 4 females were recruited in the study. Majority of the patients were above 50 years of age. Lesions were located in the oral cavity in 20, oropharynx in 4, parsnasal sinus (maxilla) in 6 and larynx in 4. In the oral cavity, 10 lesions were in alveolus, 2 in palate, 6 in tongue and 2 on lips (Table 1).

A total of 16 patients were stage III and 18 were stage IVA. Tobacco habits were present in all the cases with 28 being tobacco chewers while 6 were smokers. None of the patients had a family history of cancer and pain was present in all the cases. Four patients were diabetic (Table 1).

A total of 12 patients were node negative, 20 had N1 disease and 2 were N2a. Karnofsky performance status was 90% in 32 patients and 80% in 2 patients.

Response to chemotherapy

Complete response was observed in 2 patients and a partial response was observed in 32 patients. Both patients demonstrating a complete response had received paclitaxel with cisplatin (Table 2).

Further treatment

After the evaluation of response, 20 patients underwent surgery. Total laryngectomy was carried out in 4, hemiglossectomy in 6, wide local excision only in 2, hemi mandibulectomy in 2 and arch mandibulectomy in 6. A total of 4 patients required flap reconstruction, two of whom had very large full thickness defects. Of the 20 patients undergoing surgery only 2 were node positive (Table 2).

No surgery was performed for 14 patients, of these 13 patients received radiotherapy while 1 patient with CR refused any further treatment. He is still disease free after 2 years.


None of the patients had hematological / bone marrow toxicity. However, most patients had GI toxicity. Nausea at the end of each cycle was present in all patients; it was grade I in 20 and grade II in 14 at the end of second cycle. Vomiting was present in 23 patients at the end of first cycle while 28 had vomiting by end of third cycle (Table 3). Grade I diarrhea was present in 24 patients at end of 2nd cycle while only 14 had diarrhea at the end of third cycle. Fever without neutropenia occurred in 10 patients at the end of third cycle.

Table:2: Response to neoadjuvant chemotherapy and surgical procedures performed
Chemo Response n %
Partial response 32 94.1
Complete response 2 5.9
Post op node positivity
Positive 2 5.9
Negative 16 47.1
N0 neck 16 47.1
Primary surgery
Total Laryngectomy 4 11.8
Hemiglossectomy 6 17.6
Wide local excision 2 5.9
Hemi mandibulectomy 2 5.9
Arch Mandibulectomy 6 17.6
No surgery 14 41.2
PMMC reconstruction 2 5.9
DP reconstruction 2 5.9

Overall quality of life

At the end of three cycles a statistically significant improvement in overall quality of life was seen (Table 4). The quality of life was much better in patients receiving paclitaxel and cisplatin regimen (p = 0.009) while there was no change in overall quality of life in patients receiving paclitaxel and carboplatin (Table 5).

Table:3: Toxicity of chemotherapy
Cycle1 Cycle 2 Cycle3
n % n % n %
Nausea Grade I 13 38.3 20 58.8 26 76.5
Grade II 21 61.7 14 41.2 8 23.5
Vomiting Grade I 9 26.4 8 23.5 20 58.8
Grade II 14 41.2 12 35.3 8 23.5
Diarrhea Grade I 30 88.2 24 70.6 14 41.2
Grade II 4 11.8 4 11.8 - -
Fever Grade I - - 2 5.9 10 29.4

General Physical well being

An overall deterioration in general physical well being was observed in patients. This deterioration was statistically significant irrespective of the chemotherapy regimen.

General social and family well being

A statistically significant improvement was seen in the social and family life in patients receiving chemotherapy. The improvement was higher in patients receiving paclitaxel with cisplatin, though statistically significant improvement was observed in both groups. General emotional well being

A statistically significant deterioration was observed in patients receiving neoadjuvant chemotherapy. The deterioration was seen in both the arms, however this was higher in patients receiving carboplatin.

General functional well being

A statistically significant improvement was seen in general well being of the patients receiving neoadjuvant chemotherapy. Though seen in both chemotherapy arms, it was higher in patients receiving cisplatin combination.

Trial outcome Index

A statistically significant improvement was seen in trial outcome index, the improvement being higher in patients receiving cisplatin and taxane combination.

Discussion Chemoradiation

Although chemo radiation (CRT) is considered the standard of care for the management of locally advanced HNSCC, the novel approach of induction chemotherapy is being increasingly evaluated in numerous RCTs. for various reasons [21-27].

Table:4 Quality of life
Before chemo After 3 cycles of chemo t test p value
Mean ± SD Mean ± SD
GP 6.94±2.4 3.65±2.2 6.8 0.000
GS 18.06±1.3 19.8±1.2 -8.3 0.000
GE 16.4±0.5 4.2±0.5 128.8 0.000
GF 9.35±6.1 20.2±3.1 -16.9 0.000
HN 15.0±2.3 20.3±0.9 -17.6 0.000
Total 65.8±8.6 68.4±2.8 -2.0 0.05

Distant failure rate in CRT is high due to the fact that the dosage of chemotherapy used in CRT protocols is ineffective in tackling the distant micro metastasis. Hence, the rationale for induction chemotherapy with high dosage of same drugs is to destroy the micro metastasis.

Induction chemotherapy

Induction chemo induces tumor shrinkage to permit less toxic but more effective local therapy be it surgery or RT, leading to high rates of organ preservation. In the naive patients, optimal delivery of chemotherapy drugs to tumors occurs through a vasculature that has not been disturbed by surgery / RT.

Table:5: Quality of life by chemo regimen
Before chemo After chemo t p
G Physical 6.18±0.5 4.0±2.5 4.0 0.001
GSocial / family 17.8±1.4 20.0±1.1 -12.0 0.000
G Emotional 16.45±0.5 4.18±0.58 91.2 0.000
G Functional 8.36±6.4 20.0±3.4 -14.4 0.000
Head and neck 15.0±2.4 20.6±0.4 -13.5 0.000
Total 63.91±10.0 68.8±2.3 -2.9 0.009
Trial outcome index
29.54 44.6
Before chemo After chemo t p
G Physical 8.33±3.07 3.0±1.4 8.2 0.000
G Social / family 18.5±1.1 19.6±1.4 -2.46 0.03
G Emotional 16.5±0.5 4.33±0.4 108.2 0.000
G Functional 11.17±5.2 20.8±2.6 -9.5 0.000
Head and neck 14.8±2.2 19.8±1.4 -11.7 0.000
Total 69.3±3.8 67.6±3.4 1.3 0.197
Trial outcome index
34.3 26.0

Induction chemotherapy also permits the assessment of tumor responsiveness and hence helps us to alter subsequent therapy accordingly but intermediary assessment of response cannot be done in CRT protocols.


After its introduction in 1980, PF regimen became the standard regimen for induction chemo for locally advanced HNSCC patients with overall response rate of 60-90% and complete response rate of up to 50% [28,29].

Dana Farber Cancer Institute published four phase-II trials [15-18], evaluating the addition of docetaxel to PF based regimens which showed complete response rate in range of 42-61% and major response rate between 93-100%, with 3 year overall survival rates between 62 and 78%. High response rates with docetaxel, cisplatin, 5-FU (TPF) regimen were also seen in many studies from Europe and Japan with major response rates of 64-94% [30-33].

With the use of Paclitaxel as a single agent response rate of around 40% has been observed [34-35]. The PPF (Paclitaxel, cisplatin, and 5-FU) produced a high overall major response rate of 86-88% [19-20].

Pfreundner et al., [36] showed that paclitaxel and cisplatin in the neoadjuvant setting produced a complete response of 10% and partial response of 75% with overall major response of 90%. While, Dunphy et al.,[37] demonstrated the efficacy of paclitaxel and carboplatin in the inclusion setting with 34% complete response rate, 32% partial response rate and 66% overall major response rates.

We, in our study, observed complete response rate was 5.9% and partial response rate of 94.1% with an overall major response rate of 100%, which is a very encouraging, to be further evaluated by phase-III trials.

Local treatment after induction chemo consisted of surgery and / or EBRT. The surgeries after induction chemo were of less magnitude due to tumor shrinkage after chemo therapy, with only 4 out of 20 surgical patients requiring loco-regional flap reconstruction for the defects.


The toxicity of induction chemotherapy is much less when compared to concurrent chemo radiation due to the fact that the latter aims for intense dose density locally. The toxicities of induction chemotherapy are systemic and transient.

Paclitaxel /cisplatin regimen usually produced grade I/II nausea (51%) and vomiting (32%), grade 1 nephrotoxicity(46%), Grade I/II neurotoxicity, Grade I/II bone marrow toxicity (47%),Grade 3 alopecia(90%). Grade 3-4 toxicities were low with bone marrow toxicity (7-8%), Nausea (7-8%), fever (5-39%), nephrotoxicity (4-5%) [36].

In our study nausea, vomiting, diarrhea, and fever were the common complications encountered, with grade I nausea increasing from 13% after cycle 1 to 26% after cycle 3, grade I vomiting increasing from 9% after cycle 1 to 20% after cycle 3, but incidence of diarrhea decreasing from 30% to 14% after cycle 3. Non neutropenic fever incidence increasing from nil to 10% at the end of cycle 3. No patients in our study encountered hematological and bone marrow toxicity. No patients encountered nephrotoxicity /neurotoxicity. No severe grade III/IV toxicities were encountered.

Quality of Life

There was a statistically significant improvement in overall quality of life seen after the administration of three cycle of chemotherapy, with much better results in paclitaxel/cisplatin regimen. Although physical and emotional well being of patients deteriorated after chemotherapy, the other aspects like social and family well being, functional well being had a significant improvement.

The trial outcome index also showed a statistically significant improvement with cisplatin/paclitaxel regimen faring better probably due to better response and less toxicity of this regimen.


Although concurrent chemo radiation is the current standard of care for the treatment of locally advanced head and neck squamous cell carcinoma, induction chemotherapy regimens are also showing promising results thereby redefining its role in these patients. The induction chemotherapy regimen with paclitaxel and platinum agents (cisplatin/carboplatin) in our study showed encouraging results in terms of response (overall major response rate of 100%), low toxicity profile (No grade III/IV complications and no hematological complications), and good functional outcome scores (by improvement in FACT-HN score), thereby justifying the need for more phase III randomized controlled trials in proving the efficacy of these regimens.


The authors wish to thank Dr. David Cella, Northwestern University, USA, the developer of FACT questionnaires for his kind permission for its use in the present study.

Authors' Contributions

SK: Helped in literature search and prepared the draft manuscript.
TG: Did the literature search, helped in design of the study, collected the results, helped with analysis of results
UG: Helped with the collection of data and analysis and interpretation of the study
MS: Helped with the analysis and interpretation of results and preparation of draft manuscripts.
SP: Helped with collection of data, analysis and interpretation of results and review.
SS: helped with preparation of manuscript and editing.
MP: Conceived the idea, designed the study and edited the final manuscript.


There was no funding for this study.

Ethical approval

The study was approved by the Institute Ethics committee.


[1]. Forastiere A, Koch W, Trotti A, Sidransky D. Head and neck cancer. N Engl J Med 2001;345:1890–1900.

[2]. Posner MR, Haddad RI, Wirth L, Norris CM, Goguen LA, Mahadevan A. 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.

[3]. The Department of Veterans Affairs Laryngeal Cancer Study Group. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991;324:1685–1690.

[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;88:890–899.

[5]. Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, Glisson B, Trotti A, Ridge JA, Chao C, Peters G, Lee DJ, Leaf A, Ensley J, Cooper J. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003;349:2091–2098.

[6]. Denis F, Garaud P, Bardet E, Alfonsi M, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Calais G. Final results of the 94-01 French Head and Neck Oncology and Radiotherapy Group randomized trial comparing radiotherapy alone with concomitant radiochemotherapy in advanced-stage oropharynx carcinoma. J Clin Oncol 2004;22:69–76.

[7]. Paccagnella A, Orlando A, Marchiori C, Zorat PL, Cavaniglia G, Sileni VC, Jirillo A, Tomio L, Fila G, Fede A, et al. Phase III trial of initial chemotherapy in stage III or IV head and neck cancers: a study by the Gruppo di Studio sui Tumori della Testa e del Collo. J Natl Cancer Inst 1994;86:265–272.

[8]. Pignon JP, Bourhis J, Domenge C, Designé L.. 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 2000;355:949–955.

[9]. Wendt T, Grabenbauer G, Rodel C, Thiel HJ, Aydin H, Rohloff R, Wustrow TP, Iro H, Popella C, Schalhorn A. Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study. J. Clin. Oncol., 1998, 16: 1318–1324.

[10]. Brizel DM, Albers ME, Fisher SR, Scher RL, Richtsmeier WJ, Hars V, George SL, Huang AT, Prosnitz LR. Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N. Engl.J. Med., 1998; 338: 1798–1804.

[11]. Jeremic B, Shibamoto Y, Milicic B, Nikolic N, Dagovic A, Aleksandrovic J, Acimovic L, Milisavljevic S. 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., 2000; 18: 1458–1464.

[12]. Calais G, Alfonsi M, Bardet E, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Oudinot P, Bertrand P. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma [see comments]. J. Natl. Cancer Inst., 1999; 91: 2081–2086.

[13]. Forastiere A: Another look at induction chemotherapy for organ preservation in patients with head and neck cancer. J Natl Cancer Inst 1996; 88:855-856.

[14]. Jacobs C: Head and neck cancer in 1994: A change in the standard of care. J Natl Cancer Inst 1994, 86:250-252.

[15]. Colevas A, Busse P, Norris C, Fried M, Tishler RB, Poulin M. Induction chemotherapy with docetaxel, cisplatin, 5-fluorouracil, and leucovorin (TPFL5) for squamous cell carcinoma of the head and neck: a Phase I/II trial. J Clin Oncol. 1998; 16:1331–1339.

[16]. Colevas A, Norris C, Tishler R, Fried MP, Gomolin HI, Amrein P, Nixon A, Lamb C, Costello R, Barton J, Read R, Adak S, Posner MR. Phase II trial of docetaxel, cisplatin, 5-fluorouracil, leucovorin as induction for squamous cell carcinoma of the head and neck. J Clin Oncol. 1999;17:3503–3511.

[17]. Colevas A, Norris C, Tishler R, Lamb CC, Fried MP, Goguen LA Gopal HV, Costello R, Read R, Adak S, Posner MR. A Phase I/II Study of outpatient docetaxel, cisplatin, 5-fluorouracil, and leucovorin (op-TPFL) as induction for squamous cell carcinoma of the head and neck (SCCHN). Am J Clin Oncol. 2002;25:153–159.

[18]. Posner M, Glisson B, Frenette G, Al-Sarraf M, Colevas AD, Norris CM, Seroskie JD, Shin DM, Olivares R, Garay CA. A multi-center Phase I–II trial of docetaxel, cisplatinum, and 5-fluorouracil induction chemotherapy for patients with locally advanced Squamous cell cancer of the head and neck. J Clin Oncol. 2001;19:1096–1104.

[19]. Hitt R, Paz-Ares L, Brandariz A, Castellano D, Peña C, Millán JM, Calvo F, Ortiz de Urbina D, López E, Alvarez-Vicent JJ, Cortés-Funes H. Induction chemotherapy with paclitaxel, cisplatin and 5-fluorouracil for squamous cell carcinoma of the head and neck: long-term results of a phase II trial. Ann Oncol 2002;13:1665–1673.

[20]. Hitt R, Jimeno A, Millan JM, Castellano D, Cortés-Funes H. Phase II trial of dose-dense paclitaxel, cisplatin, 5-fluorouracil, and leucovorin with filgrastim support in patients with squamous cell carcinoma of the head and neck. Cancer 2004;101:768–775.

[21]. Browman, GP. Evidence -based recommendations against neoadjuvant chemotherapy for routine management of patients with squamous cell head and neck cancer. Cancer Invest 1994; 12:662-670.

[22]. Vokes, EE, Haraf, DJ, Weichselbaum, RR, Brachman, D. Induction chemotherapy: Promises and limitations. In: Head and Neck Cancer, Johnson, JT, Didolkar, MS (Eds), Amsterdam, Exerpta Medica 1993; 321-326.

[23]. Specenier PM, Vermorken JB. Neoadjuvant chemotherapy in head and neck cancer: should it be revisited?. Cancer Lett 2007; 256:166-177.

[24]. Beitler JJ, Cooper JS. Seduction by induction? J Clin Oncol 2009; 27:9-10.

[25]. Ozols RF, Masuda H, Hamilton TC. Keynote address: Mechanisms of cross-resistance between radiation and antineoplastic drugs. NCI Monogr 1988; 6:159-165.

[26]. Ensley JF, Jacobs JR, Weaver A, Kinzie J, Crissman J, Kish JA, Cummings G, Al-Sarraf M. Correlation between response to cisplatinum-combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck. Cancer 1984; 54:811-814.

[27]. Rosenthal DI, Pistenmaa DA, Glatstein E. A review of neoadjuvant chemotherapy for head and neck cancer: Partially shrunken tumors may be both leaner and meaner. Int J Radiat Oncol Biol Phys 1994; 28:315-320.

[28]. Monnerat C, Faivre S, Temam S, Bourhis J, Raymond E. End points for new agents in induction chemotherapy for locally advanced head and neck cancers. Ann Oncol 2002;13:995–1006.

[29]. Rooney M, Kish J, Jacobs J, Kinzie J, Weaver A, Crissman J, Al-Sarraf M. Improved complete response rate and survival in advanced head and neck cancer after three-course induction therapy with 120-hour 5-FU infusion and cisplatin. Cancer 1985;55:1123–1128

[30]. Janinis J, Papadakou M, Panagos G, Panousaki A, Georgoulias V, Hatzidaki D, Lefantzis D, Dokianakis G. Sequential chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil in patients with locally advanced head and neck cancer. Am J Clin Oncol 2001;24:227–231.

[31]. Schrijvers D, Van Herpen C, Kerger J, Joosens E, Van Laer C, Awada A, Van den Weyngaert D, Nguyen H, Le Bouder C, Castelijns JA, Kaanders J, De Mulder P, Vermorken JB. Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study. Ann Oncol 2004;15:638–645.

[32]. Tsukuda M, Mikami Y, Tanigaki Y, Katori H, Horiuchi C, Ikeda Y, Taguchi T, Ono M, Yoshida T, Sakuma Y, Aikoh K. Phase I trial of combined chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for patients with locally advanced squamous cell carcinoma of the head and neck. Int J Clin Oncol 2004;9:161–166.

[33]. Watanabe A, Taniguchi M, Sasaki S. Induction chemotherapy with docetaxel, cisplatin, fluorouracil and l-leucovorin for locally advanced head and neck cancers: a modified regimen for Japanese patients. Anticancer Drugs 2003;14:801–807

[34]. Forastiere AA, Shank D, Neuberg D, Taylor SG 4th, DeConti RC, Adams G. Final report of a phase II evaluation of paclitaxel in patients with advanced squamous cell carcinoma of the head and neck: an Eastern Cooperative Oncology Group trial (PA390). Cancer 1998;82:2270–2274.

[35]. Smith RE, Thornton DE, Allen J. A phase II trial of paclitaxel in Squamous cell carcinoma of the head and neck with correlative laboratory studies. Semin Oncol 1995;22(suppl 6):41–46.

[36]. Pfreundner L, Hoppe F, Willner J, Preisler V, Bratengeier K, Hagen R, Helms J, Flentje M. Induction chemotherapy with paclitaxel and cisplatin and CT-based 3D radiotherapy in patients with advanced laryngeal and hypopharyngeal carcinomas—a possibility for organ preservation. Radiotherapy and Oncology 2003 68 : 163–170

[37]. Dunphy FR, Dunleavy TL, Harrison BR, Trinkaus KM, Kim HJ, Stack BC Jr, Needles B, Boyd JH. Induction paclitaxel and carboplatin for patients with head and neck carcinoma. Analysis of 62 patients treated between 1994 and 1999. Cancer 2001;91: 940–948.