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Year : 2015  |  Volume : 52  |  Issue : 1  |  Page : 65--68

A prospective study to assess the efficacy and toxicity of 5-flurouracil and cisplatin versus taxane and cisplatin as induction chemotherapy in locally advanced head and neck squamous cell cancer in a regional cancer center in India

KC Lakshmaiah, AH Rudresha, TM Suresh, D Lokanatha, GK Babu, LA Jacob 
 Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India

Correspondence Address:
A H Rudresha
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka


Aim: The aim of this study is to assess the efficacy and toxicity of 5-flurouracil (5-FU) and cisplatin (PF) versus taxane and cisplatin (TP) as induction chemotherapy in locally advanced head and neck squamous cell cancer. Materials And Methods: There were 50 patients in each arm, matched for age, performance state, site and stage of disease. PF arm (cisplatin - 100 mg/m2 D1, 5-FU - 1000 mg/m2 D1-D5) TP arm (docetaxel - 75 mg/m2 or paclitaxel - 175 mg/m2 on D1, cisplatin 75 mg/m2 on D2), received once in 3 weeks for 3 cycles. Patients without progressive disease underwent either surgery or chemoradiation. The primary end point was overall response rate (ORR) and secondary endpoint was toxicity. Results: In a total of 100 patients in our study, 44 in PF and 47 in TP arm were evaluable. ORR was 86.6% in PF arm and 82.9% in TP arm (P = 0.71).There were more Grade 3 or 4 events of neutropenia, mucositis (P ≤ 0.05) and myelosuppression diarrhea, febrile neutropenia (P ≥ 0.05) in PF arm compared with TP arm. Post-chemotherapy hospital admissions due to toxicity were more frequent in PF arm (38.6% vs. 19%), dropout rate due to toxicity (9% vs. 0%) and deaths (6.8% vs. 2.1%) were more common in PF arm compared with TP arm. Conclusion: TP induction chemotherapy better tolerated than PF, which has similar efficacy, further multicenter randomized controlled studies; involving a large sample size is needed to confirm our data.

How to cite this article:
Lakshmaiah K C, Rudresha A H, Suresh T M, Lokanatha D, Babu G K, Jacob L A. A prospective study to assess the efficacy and toxicity of 5-flurouracil and cisplatin versus taxane and cisplatin as induction chemotherapy in locally advanced head and neck squamous cell cancer in a regional cancer center in India.Indian J Cancer 2015;52:65-68

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Lakshmaiah K C, Rudresha A H, Suresh T M, Lokanatha D, Babu G K, Jacob L A. A prospective study to assess the efficacy and toxicity of 5-flurouracil and cisplatin versus taxane and cisplatin as induction chemotherapy in locally advanced head and neck squamous cell cancer in a regional cancer center in India. Indian J Cancer [serial online] 2015 [cited 2022 May 22 ];52:65-68
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Full Text


Head and neck cancer accounts for 30% of all cancers in India compared with <10% in the western world and <3% in USA. In India majority of squamous cell head and neck cancers present with locally advanced disease with poor nutritional and performance status. For many years radiotherapy has been the treatment of choice for unresectable disease,[1] with 5-year survival rate of <20%. Concurrent chemoradiation has now largely replaced radiotherapy alone in the treatment of unresectable squamous-cell carcinoma of the head and neck,[1],[2] but induction chemotherapy has also been associated with a survival benefit and could be a valuable treatment option in locally advanced disease.[3],[4]

A beneficial effect of induction chemotherapy has been observed with the Wayne State University regimen of cisplatin (100 mg/m 2) plus infusional 5-fluorouracil (5-FU) (1000 mg/m 2 for 5 days), which has emerged as the most active combination chemotherapy.[5] Taxanes have also shown efficacy in the management of squamous cell carcinoma of head and neck.[6]

As most of the head and neck cancer patients presents with advanced stage surgery not feasible. Hence they require induction chemotherapy to downstage the disease, followed by definitive surgery or chemoradiation.[5],[7] Because of toxicity most of our patients do not tolerate the three drug regimen, which has been the standard of care today.[8] As shown in the prior study conducted at our center comparing three drug regimen of taxane, cisplatin and 5-FU (TPF) versus two drug regimen of cisplatin and 5-FU (PF), the overall response rate (ORR) was 90% with TPF and 84.4% with PF, which was not statistically significant (P = 0.73). The Grade 3 and 4 toxicity was more common with TPF arm compared with PF arm.

Toxicity associated with PF regimen was also more, hence this study is undertaken to compare the safety and efficacy of 5-FU and cisplatin versus taxane and cisplatin in locally advanced head and neck squamous cell cancer.

 Materials and Methods

This was an open-label prospective study. All the known variables were well-matched in both groups. The protocol was approved by the departmental review board and written informed consent was obtained from all the patients.

Inclusion criteria

Age 18-60 years Chemo naïve pathologically proven head and neck squamous cell carcinoma Stage 3 or non-metastatic Stage 4 disease with ≥1 measurable lesion Eastern cooperative oncology group performance status (ECOG PS) ≤2 Normal hematologic, renal and hepatic functions.

Exclusion criteria

Stage 1, 2 and metastatic Stage 4 head and neck cancer Nasopharyngeal and Esophageal carcinoma Histology other than squamous cell carcinoma ECOG PS ≥3 History of another malignancy Any renal or hepatic dysfunction or pre-exiting neuropathy ≥ grade 2 common toxicity criteria.

Study method

The study enrolled the patients from December 2010 to February 2012. Patients were assigned to study groups after the eligibility criteria were met. Both treatment arms were matched for all known variables. A total of 100 patients were enrolled and were divided into two arms with 50 patients in each arm.

PF arm

Cisplatin - 100 mg/m 2 day 1 5-FU - 1000 mg/m 2 day 1-5.

TP arm

Paclitaxel - 175 mg/m 2 or docetaxel - 75 mg/m 2 on day 1 Cisplatin - 75 mg/m 2 on day 2.

During chemotherapy, patients were monitored clinically, complete hemogram and serum biochemistry on day 0 of each cycle.

All patients received adequate premedication with antiemetics, Dexamethasone and H2-blocker. In TP arm all patients received oral dexamethasone (8 mg twice daily) starting from the previous night of the next cycle to a total of six doses to prevent hypersensitivity reaction, fluid retention and skin toxicity. All patients were planned for 3 cycles; each cycle was repeated once in 3 weeks.

Prophylactic antibiotic (oral ciprofloxacin 500 mg twice a day) was given to all the patients from day 5 to day 15 of each cycle. No prophylactic granulocyte colony stimulating factor (G-CSF) was given in either arm in the first cycle. G-CSF was added in subsequent cycles if they had develop febrile neutropenia or a delay in recovery of the absolute neutrophil count at day 28 or Grade 4 neutropenia persisting for 7 days or more. If a patient develops any complication during the course of treatment, it was managed accordingly and chemotherapy was delayed until the recovery of patient with complete resolution of mucositis for at least 7 days and laboratory parameter meeting the inclusion criteria with hemoglobin ≥10 g/dl, absolute neutrophil count ≥1500 cells/mm3; platelet count ≥1 lakh cells/mm3; and normal renal (serum creatinine ≤1.5 mg/dl) and hepatic functions (aspartate aminotransferase and alanine transaminase enzyme level ≤3 times the upper limit of the normal range and serum bilirubin level ≤1.5 mg/dl).

Study end points

Primary end point-tumor response rate. Secondary end point-toxicity for the maximum three cycles.


Efficacy: Responses were assessed using revised Response Evaluation Criteria in Solid Tumor criteria (version 1.1).

Safety: Analysis was performed using Common Terminology Criteria for Adverse Events (version 4.0).

Statistical analysis

A two-sided level of significance of P = 0.05 was applied to all tests. An unadjusted Chi-square test was used to compare response variables.


There were 50 patients in each arm. A total of 44 patients (six voluntarily withdrawn from the study) in PF arm and 47 (three voluntarily withdrawn from the study) patients in TP arm were available for analysis. All were matched for age, sex, site, performance status and stage [Table 1].{Table 1}

Median age of the presentation was 46 years in PF arm and 47 years in the TP arm. Most of them were males in both the arms (M: F was 1.9:1).

Tumor characteristics

The most common site of malignancy was oral cavity (37.3%) followed by oropharynx (32.9%), hypopharynx (19.7%) and larynx (9.8%). Nearly, 88% of the patients presented in non-metastatic Stage 4 disease and 12% in Stage 3 disease [Table 2].{Table 2}


Total numbers of chemotherapy cycles received were 106 in PF arm and 126 in TP arm. ORR was 86.6% in PF arm and 82.9% in TP arm, which was not statistically significant (P = 0.71). Nearly, 6.8% of patients on PF regime progressed on chemotherapy, while in TP arm 8.5% of patients had progressive disease, which was not significant statistically (P = 0.76). Discontinuation of chemotherapy due to toxicity was seen only in PF arm (9%). Dose modification (5-FU dose reduced by 25%) was carried out in 25% of the cases in PF arm and 8.8% in TP arm (docetaxel dose decreased to 60 mg/m2 and paclitaxel to 150 mg/m 2), addition of G-CSF was required more in PF arm compared TP arm (38.6% vs. 14.8% P = 0.01) which was statistically significant. There was no significant difference in patients who undergone definitive treatment either surgery or chemo-RT in both groups [Table 3].{Table 3}

Comparing the patients who responded to induction chemotherapy to non-responders between two arms by logistic regression was not significant (P ≤ 0.05) with odds ratio of 0.80. All the variables included in the regression model were not significant, with odds ratio of each variable age (0.95), sex (2.2), performance status (0.83), stage (0.99) and site (0.87). Hence, there was no difference in the efficacy between the two arms.

Toxicity profile

The most common toxicity was neutropenia and lethargy in both arms. Neutropenia (40.5% vs. 21.4%), mucositis (35.8% vs. 16.6%) and post-chemotherapy hospital admissions (38.6% vs. 19%) were more common in PF arm compared with TP arm which were statistically significant. While other toxicities were also more commonly seen in PF arm, compared with TP arm, which were not significant statistically. One patient in TP arm had developed Grade 3 peripheral neuropathy, with residual deformity at the end of 6 month, none in PF arm. More number of patients in PF arm admitted to a hospital due to post chemotherapy toxicity (38.6% vs. 19%) compared with TP arm there were three (6.8%) deaths in PF arm as compared with one (2.1%) death in TP arm. In a subset analysis there was no significant difference in efficacy or toxicity between docetaxel and paclitaxel [Table 4].{Table 4}


Our study showed that induction chemotherapy with TP resulted in similar improvements in response rate, as compared with PF, in locoregionally advanced, unresectable squamous-cell carcinoma of the head and neck.

Selection of the TP regimen that was used in this study was based on results of an earlier phase 2 study, which revealed similar activity with much less hematologic and overall toxicity, thus providing a safer regimen with equal efficacy.[9],[10]

Primary end point of our study was ORR associated with each regimen. ORR is almost similar between the both the arms and was also similar to other trials.[11]

Among the secondary end points, Neutropenia, mucositis and post-chemotherapy hospital admissions were more common in PF arm compared with TP arm.

Toxicity profile of our study almost similar to the recently conducted phase 3 trials where in more toxicity events such as fatigue, myelosuppression and deaths occurred in PF arm compared with TP. In our study infections rate, mucositis in PF arm was 23.5%, 35.8% respectively in their study it was 21% and 31% which was almost similar. Likewise in TP arm infection rate, mucositis was 12.6% and 16.6% respectively in our study compared with 12% and 10.6% in their trial.[12]

Most of our head and neck patient's presents with advanced stage and poor performance status. The most important clinical consideration, apart from the toxicity of induction therapy is that a certain number of patients receiving induction chemotherapy does not proceed to receive definitive therapy, due to dropout related to death and toxicity.

In early randomized studies of induction chemotherapy followed by definitive treatment, the number of patients who did not comply with treatment were greater in the chemotherapy groups, which was the likely cause of an inferior outcome of patients receiving induction chemotherapy.[13] In a Phase 3 study by Hitt et al., the drop rate was 13% (not received the definitive treatment) in TPF arm and still more in PF arm.[14] The dropout rate due to toxicity and death related to induction chemotherapy in advanced head and neck cancer was 16.2% in PF arm and 10.9% in TPF arm in a study conducted by Vermorken et al.[8] These dropout rates in addition to deaths due to toxicity are likely to negate any potential benefit by induction chemotherapy.[15] In our study, dropout rate due to toxicity and death was 15.9% (4 cases due to toxicity, three deaths) in PF arm and only 2.1% (1 death) in TP arm. Hence more number of patients on TP arm completed definite treatment compared with PF arm.

So induction therapy to be more effective it should be less toxic and at the same time should retain its efficacy. So that more number of patients will proceed to receive definitive treatment because of fewer drop out because of less morbidity and mortality.

Duration of hospital stay during chemotherapy was 5 days in PF arm, while 2 days in TP arm; hence there was less hospital stay, which reduced the cost of chemotherapy administration in TP arm.

To conclude taxane and cisplatin combination chemotherapy is better tolerated than cisplatin and 5-FU with similar efficacy. Due to less toxicity, there was a fewer dropout in TP regime hence more number of patients received definitive treatment.

Further multicenter randomized controlled studies involving a large number of patients required to formulate the better induction chemotherapy regime in the head and neck cancer.


I would like to thank Dr. Lokesh KN who gave great support in completing this article and all the staff members and postgraduate students from the Department of Medical Oncology, Department of Oral Surgery, Department of Head and Neck Oncology, Department of Radiotherapy, Department of Radiology, nursing and paramedical staff for their immense help and support in doing this study and preparing the manuscript.


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