ISSN: 2320-5407 Int. J. Adv. Res.

12(09), 920-928

Journal Homepage: -www.journalijar.com

Article DOI:10.21474/IJAR01/19525
DOI URL: http://dx.doi.org/10.21474/IJAR01/19525

RESEARCH ARTICLE
Efficacy of Induction Chemotherapy with Paclitaxel and Carboplatin in Locally Advanced Squamous Cell
Carcinoma of the Hypopharynx: A Descriptive Case Series

Dr. Kiran Shahzadi, MBBS, FCPS, Dr. Mohammad Faheem, MBBS, FCPS, MCPS, Dr. Um-e Lela, PhD
and Baneeha Zainab, M.Phil.
……………………………………………………………………………………………………....
Manuscript Info Abstract
……………………. ………………………………………………………………
Manuscript History Introduction: Head and neck cancer including hypopharyngeal
Received: 25 July 2024 carcinoma is one of commonest malignancies in Pakistan. According to
Final Accepted: 27 August 2024 the Pakistan Medical Research Council (PMRC) reports, it was found
Published: September 2024 to be the commonest malignancy in males and was second highest to
breast cancer in females. The patients for the management of
Key words:-
Hypopharyngeal Carcinoma, Dysphagia, hypopharyngeal cancer present with locally advanced disease.
Induction Chemotherapy Induction chemotherapy with paclitaxel and carboplatin is being used
for few years but the results have not been documented yet. The aim of
this study is to design a protocol in future with improved outcome and
acceptable morbidity.
Objective:To determine the efficacy of induction chemotherapy with
paclitaxel & carboplatin in locally advanced squamous cell carcinoma
of hypopharynx in terms of frequency of complete and partial response.
Settings:This study was conducted at Nuclear Medicine, Oncology and
Radiotherapy Institute (NORI), Islamabad.
Study Design: Descriptive case series.
Duration of study: 6 months from 01/08/2017 to 31/01/2018
Material and methods:In this study a total of 59 patients were
observed by using World Health Organization sample size calculator
where confidence level: 95%, anticipated population proportion: 67%,
relative precision: 12%. Moreover, nonprobability consecutive
sampling technique was used for sample collection.
Results:Mean age was 60 ± 11.87 years. 40(68%) patients were males
while 19(32%) were females. 22(38%) patients had carcinoma of stage
III, 32(54%) patients had carcinoma of stage IVA while 5(8%) patients
had carcinoma of stage IVB. Moreover, induction chemotherapy was
effective in 42(72%) patients and was not effective in 17(28%) patients.
Conclusion:Our study concludes that induction chemotherapy with
paclitaxel & carboplatin was 72% effective in locally advanced
squamous cell carcinoma of hypopharynx in terms of frequency of
complete and partial response.

Copyright, IJAR, 2024,. All rights reserved.

……………………………………………………………………………………………………....
Introduction:-
Head and neck cancer including hypopharyngeal carcinoma is one of commonest malignancies in Pakistan.
According to the Pakistan Medical Research Council (PMRC) reports, it was found to be the commonest

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Corresponding Author:-Dr. Kiran

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malignancy in males and was second highest to breast cancer in females. There are multiple treatment modalities
available these days but despite that the overall survival of patients has not improved significantly during the past
two decades, with the 5-year survival rates between 45- 50%1. Hypopharyngeal carcinoma is not very common in
developed countries, in United States, approximately 2,500 new cases are diagnosed every year2. According to a
retrospective cohort study conducted by Kuo et al, there was a decrease in the hypopharyngeal carcinoma incidence
in the United States by an average of -2.0% annually between 1973 and 20103.

Hypopharyngeal carcinoma affects males more than females with a ratio of 2:1 to 4:1. The incidence rate in males is
higher in Hong Kong, France, the Indian subcontinent, central & eastern Europe, Brazil, Spain, Italy & among
African Americans in United States4.

Most patients with hypopharyngeal carcinoma remain symptoms free until their disease gets advanced, at
presentation many patients have metastases in lymph nodes (50-70% cases) & distant organs. In approximately 50%
of patients, the main presenting complaint is enlarged cervical lymph node. The above-mentioned study conducted
by Kuo et al found that 5-year survival rate for hypopharyngeal cancer rose significantly from 1988-1990 but there
were no significant changes in survival rates for other years.

The best treatment for hypopharyngeal carcinoma aims for the highest locoregional control rate with the least
functional damage. All advanced stage patients of hypopharyngeal cancer should be evaluated by a multidisciplinary
team before starting treatment with the goals of educating the patient and family about all the treatment options,
their outcome and side effects. With the help of a multidisciplinary team, the management and survival of the patient
can be improved5.

Induction chemotherapy followed by definitive radiotherapy offers functional organ preservation in locally
advanced hypopharyngeal cancer. The incidence of distant metastases may be decreased with induction
chemotherapy compared with radiotherapy alone and it showed a better, although not statistically significant,
survival outcome versus concurrent chemoradiotherapy in RTOG 91-116.Induction chemotherapy followed by
radiotherapy may afford larynx preservation without jeopardizing survival in pyriform sinus region cancer7.In a
study conducted by Frank R. Dunphy, induction chemotherapy with paclitaxel & carboplatin was administered in
head and neck cancer patients that was well tolerated by patients & response rate was encouraging considering most
patients were stage IV. Overall complete and partial response rate was 67% in hypopharyngeal cancer patients.
Organ preservation was also possible. Sample size was calculated from this study, adding up of complete and partial
response8.

At NORI most of the patients diagnosed with hypopharyngeal cancer are present with locally advanced disease.
Induction chemotherapy with paclitaxel and carboplatin has been used for a few years but the results have not been
documented yet. The aim of this study is to design a protocol in future with improved outcome and acceptable
morbidity.

Literature Review:-
Hypopharyngeal Carcinoma
The hypopharynx, or laryngopharynx, is the longest and most inferior portion of the 3 segments of the pharynx and
links the oropharynx to the esophagus. It is located posterior to the cartilaginous structures of the larynx 1. It is
superiorly wide and progressively narrows towards the level of the cricopharyngeal muscle. The hypopharynx is a
continuous area; the oropharynx is above it and the cervical esophagus through the cricopharyngeal sphincter is
below it. This region is known as the pharyngoesophageal junction or postcricoid area. It is bounded anteriorly by
the posterior face of the cricoid cartilage.2 The hypopharynx extends from the hyoid bone to the cricoid cartilage and
is further subdivided into the regions of the pyriform sinus, pharyngeal wall, and posterior cricoid.1, 2
o Level I: The posterior border is defined by the posterior edge of the submandibular gland.
o Level II: The superior extent is defined by the mastoid tip and the caudal edge of the lateral C1 process.
The inferior extent is defined by the cranial edge of the hyoid bone. The lateral edge is bordered by the
sternocleidomastoid muscle.
o Level III: This cervical nodal group is bordered anterolaterally by the sternocleidomastoid muscle and
begins superiorly at the cranial edge of the hyoid bone. The inferior edge is bordered by the inferior edge of the
cricoid cartilage.

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o LevelIV: This cervical nodal group is bordered by the sternocleidomastoid muscle, begins at the inferior
edge of the cricoid cartilage, and extends to 2cm superior to the supraclavicular joint.
o LevelV: This posterior neck chain is defined anteriorly by the posterior edge of the sternocleidomastoid
and the scalene muscle. It begins superiorly at the cranial edge of the hyoid bone and inferiorly at the transverse
cervical vessels.
o LevelVI: This nodal group is defined superiorly by the caudal edge of the thyroid gland and inferiorly by
the sternal manubrium. It is defined laterally by the medial edge of the sternocleidomastoid muscle and medially by
the trachea. It is limited posteriorly by the common carotid artery.6

The intimate association between the hypopharynx and the larynx, oropharynx, and esophagus allows for certain
dissemination routes of malignant disease. Pyriform sinus carcinomas may spread submucosally into the posterior
wall of the hypopharynx, the post cricoid region, or the aryepiglottic fold. Large tumors also extend up into the
paraglottic fat, the pre-epiglottic fat, and the base of the tongue. Tumors that arise from the lateral wall or apex of
the pyriform sinus often have already invaded the thyroid cartilage. Lesions of the medial wall of the pyriform sinus
may spread along the aryepiglottic fold into the false vocal cord and arytenoid cartilage. Medial wall lesions
occasionally invade paraglottic and pre-epiglottic fat. They may also grow posteriorly into the postcricoid region
and then cross the midline to involve the contralateral pyriform sinus7,8

An analysis of the Surveillance Epidemiology and End Results (SEER) database demonstrates that the incidence of
hypopharyngeal cancers decreased 35% from 1975 to 2001. 25,26 The mortality rate due to hypopharyngeal cancers
also decreased by 30%. This epidemiologic change is believed to be due to a decrease in the initiation of cancer in
the hypopharynx and does not necessarily reflect any improvement in survival due to treatment. Cancer that arises in
the hypopharynx represents approximately 7% of all cancers of the upper aerodigestive tract. The incidence of
laryngeal cancer is 4-5 times that of hypopharyngeal cancer. All pharyngeal subsites accounted for approximately
124,000 cancer cases worldwide in 2002.27.

Objective:-
To determine the efficacy of induction chemotherapy with paclitaxel & carboplatin in locally advanced squamous
cell carcinoma of hypopharynx in terms of frequency of complete and partial response.

Operational Definitions:
Induction Chemotherapy:
Induction chemotherapy refers to the use of chemotherapy for the initial treatment of advanced cancers to make
subsequent treatment (as surgery or radiotherapy) more effective.

Methodology:-
Settings:
Study was conducted at Nuclear Medicine, Oncology and Radiotherapy Institute (NORI), Islamabad.

Study Design:
Descriptive case series.

Duration of study:
6 months, 01/08/2017 to 31/01/2018.

Sample size:
Using World Health Organization sample size calculator, where Confidence level: 95%,
Anticipated population proportion: 67%, Relative precision: 12, Sample size was 59 8

Sampling technique:
Non–probability consecutive sampling

Sample Selection:
Inclusion criteria: Age 20-70 years
2: Karnofsky performance status > 70%

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3: Stage III, IVA & IVB

4: Newly diagnosed histopathological proven squamous cell carcinoma of hypopharynx
Exclusion criteria:
1: Uncontrolled hypertension and diabetes
2: Patients with abnormal RFTs and LFTs.
3: Coexisting second malignancy.
4: Patients with metastatic or recurrent disease

Data Collection Procedure:-

The study was approved by the Hospital Ethical Review Committee on 1st June 2017 and RTMC.A written informed
consent was taken from every patient fulfilling the inclusion criteria. Premenopausal patients were explained
regarding secondary amenorrhea following treatment.

Patients included in the study were those registered in the Oncology Department of NORI Hospital. They were
evaluated in detail by me with history, physical examination, investigations including Hematology, Biochemistry, 24
hours urine for creatinine clearance, Chest X Ray, upper GI endoscopy, CT Scan face & neck and echocardiography.
Consultant Radiologist reported all the radiological investigations. Every patient was discussed in multidisciplinary
meetings (MDM) involving Oncology Department NORI hospital and Surgery, E.N.T, Radiology and Pathology
department of Pakistan Institute of Medical Sciences Islamabad, Federal Govt. Services Hospital and Holy family
Hospital. All the patients received injection Paclitaxel 175mg/m2 I/V 3 hours infusion on Day 1 of chemotherapy
with premedication and post medication and injection Carboplatin AUC (GFR+25) I/V 1 hour infusion. The cycle
was repeated after every third week. Patients were given 3 cycles of chemotherapy. Toxicity was evaluated
according to WHO criteria. At grade 3-4 renal, hematological, or gastrointestinal toxicity, treatment was withheld
until complete resolution of toxicity occurred and was resumed later on with dose modification. Final response was
evaluated four weeks after completion of the third cycle with the help of clinical examination & CT scan of the head
& neck according to RECIST criteria for response assessment. All the data was recorded on the proforma attached in
the end. Follow up was ensured by taking contacts of these patients.

Data Analysis:-
The collective data was entered and analyzed using SPSS V 16. Descriptive statistics were calculated for both
qualitative and quantitative variables. Qualitative variables include gender, stage and efficacy of induction
chemotherapy and these were presented as frequency /percentages. Quantitative variables include age was presented
by mean +_SD. Age, gender and stage of carcinoma were controlled by stratification. Post stratification chi-square
test was applied and p value ≤ 0.05 was significant. Tables and charts were made for qualitative variables.

Results:-
In this study age distribution among 59 patients was analyzed as 6 (10%) patients were in age range 40-50 years,
22(37%) patients were in age ranged 51-60 years, 31(53%) patients were in age ranged 61-70 years. Mean age was
60 years with standard deviation ± 11.87. (Table No. 1)

Gender distribution among 59 patients was analyzed as 40(68%) patients were males while 19(32%) patients were
females. (Table No. 2)

Stages of carcinoma among 59 patients were analyzed as 22(38%) patients had carcinoma of stage III, 32(54%)
patients had carcinoma of stage IVA while 5(8%) patients had carcinoma of stage IVB. (Table No. 3)

Efficacy of induction chemotherapy among 59 patients was analyzed as induction chemotherapy was effective in
42(72%) patients and was not effective in 17(28%) patients. (Table No. 4)

Stratification of efficacy of induction chemotherapy with respect to age, gender and stages of carcinoma is given in
table no 5, 6, 7.

Discussion:-
Head and neck cancer including hypopharyngeal carcinoma is one of commonest malignancies in Pakistan.
According to the Pakistan Medical Research Council (PMRC) reports, it was found to be the commonest

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malignancy in males and was second highest to breast cancer in females. There are multiple treatment modalities
available these days but despite that the overall survival of patients has not improved significantly during the past
two decades, with the 5-year survival rates between 45- 50%1. Hypopharyngeal carcinoma is not very common in
developed countries, in United States, approximately 2,500 new cases are diagnosed every year2. According to a
retrospective cohort study conducted by Kuo et al, there was a decrease in the hypopharyngeal carcinoma incidence
in the United States by an average of -2.0% annually between 1973 and 20103.

Our study shows that among 59 patients, 40(68%) patients were males while 19(32%) were females. 6(10%)
patients were in the age range 40-50 years, 22(37%) patients were in age range 51-60 years, 31(53%) patients were
in age range 61-70 years. Mean age was 60 years with SD ± 11.87. 22(38%) patients had carcinoma of stage III,
32(54%) patients had carcinoma of stage IVA while 5(8%) patients had carcinoma of stage IVB. 24(41%) patients
had complete response, 18(30%) patients had partial response, 10(17%) patients had stable disease, 7(12%) patients
had progressive disease. Induction chemotherapy was effective in 42(72%) patients in terms of frequency of
complete and partial response and was not effective in 17(28%) patients.

In a study conducted by Dunphy FR et al112, induction chemotherapy with paclitaxel & carboplatin was administered
in head and neck cancer patients that was well tolerated by patients & response rate was encouraging considering
most patients were stage IV. Overall complete and partial response rate was 67% in hypopharyngeal cancer patients.
Organ preservation was also possible. Sample size calculated from this study, adding up of complete and partial
response8.

In another study23 had reported that the median follow-up time of this cohort was 43.4 months (range; 6.9–151.0).
The 3-year overall survival, progression-free survival and larynx preservation survival rates were 78.8% (95%
confidence interval; 73.0–85.0), 58.4% (95% confidence interval; 51.8–65.9) and 67.5% (95% confidence interval;
61.0–74.7), respectively. Multivariate analyses identified the following significant prognostic factors: an advanced
age, the T category and N category for overall survival, the T category and N category for progression-free survival
and the T category for larynx preservation survival. Acute toxicities of Grade 3 or higher were observed in 47
patients (23.0%). Two patients (1.0%) had Grade 4 pharyngeal edema. Suspicious treatment-related death due to
lethal pharyngeal hemorrhage occurred in 1 (0.4%) patient. The rates of Grade 2 xerostomia in patients treated with
intensity-modulated radiotherapy were 28.1, 17.4 and 9.5% at 6 months, 1 and 2 years after the completion of
radiotherapy, respectively.

In another study Iqbal H et al114 had reported that response to induction chemotherapy: complete response (CR) 58
(13%), partial response (PR) 315 (71%), stable disease (SD) 55 (12%) and progressive disease (PD) 18 (4%).
Response to RT/CRT; CR 293 (66%) and persistent disease at 3 months post treatment in 153 (34%) patients. Grade
3 and 4 toxicities for induction chemotherapy was anemia 2%/0%, neutropenia 17%/4%, thrombocytopenia 2%/1%,
vomiting 5%/1% and diarrhea 5%/1%. Grade 1 transient elevation of ALT/ AST was 17% /11%. Grade 3-4
elevation of creatinine was 2 %/1%. Nine patients (2%) had toxicity related hospital admissions during RT/CRT.
The 5- and 10-year OS, DFS and RFS were 56%, 53%, 45%, 41%, 30% and 27% respectively. 149 (33%) patients
are alive, disease free and maintaining routine follow up.

Conclusion:-
Our study concludes that induction chemotherapy with paclitaxel & carboplatin was 72% effective in locally
advanced squamous cell carcinoma of hypopharynx in terms of frequency of complete and partial response.The
study demonstrates that induction chemotherapy with paclitaxel and carboplatin shows a 72% efficacy rate in
achieving complete or partial response in patients with locally advanced squamous cell carcinoma of the
hypopharynx. These findings suggest that this chemotherapy regimen can be a viable option for reducing tumor size
and improving patient outcomes in this specific patient cohort.

Implications
1. Clinical Practice: These findings could encourage oncologists to consider this chemotherapy combination as a
part of the treatment protocol for similar patient groups, potentially improving initial treatment responses.
2. Future Research: The study highlights the need for randomized controlled trials with larger and more diverse
populations to confirm these results and assess long-term survival and quality of life.
3. Patient Education: Improved patient education regarding treatment options and expected outcomes can be
derived from this study, aiding in informed decision-making.

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Table1:- Distribution of Involved Lymph Nodes.

Site Submaxillay (Level Upper Jugular Mid Jugular (Level Lower Jugular (Level IV), %
I), % (Level II), % III), %

Pharyngeal wall 20 80 40 40
Pyriform sinus 0 67 33 7
*As found after elective modified neck dissection by Byers et al[6]

Figure 1:- Source Google (Posterior View of the Pharynx).

Table No. 2:-Age Distribution (n=59).

AGE FREQUENCY PERCENTAGE
40-50 years 6 10%
51-60 years 22 37%
61-70 years 31 53%
Total 59 100%
Mean age was 60 years with standard deviation ± 11.87

Table No. 3:-Gender Distribution (n=59)

GENDER FREQUENCY PERCENTAGE
Male
40 68%
Female 19 32%
Total 59 100%

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Figure2:- Source Google (Anterior View of the Larynx and Pharynx).

Table No. 4:- Stages Of Carcinoma(n=59)

STAGE OF CARCINOMA FREQUENCY PERCENTAGE
Stage III 22 38%
Stage IV A 32 54%
Stage IV B 5 8%
Total 59 100%

Table No. 5:-Follow Up After 4 Weeks (n=59).

Follow up after 4 weeks FREQUENCY PERCENTAGE
Complete response 24 41%
Partial response 18 30%
Stable disease 10 17%
Progressive disease 7 12%
Total 59 100%

Table No. 6:- Efficacy Of Induction Chemotherapy (n=59) .

EFFICACY FREQUENCY PERCENTAGE
Effective 42 72%
Not effective 17 28%
Total 59 100%

Table No. 7:-Stratifications Of Efficacy Of Induction Chemotherapy W.R.T Age Distribution (n=59).
EFFICACY 40-50 years 51-60 years 61-70 years Total
Effective 4 16 22 42
Not effective 2 6 9 17
Total 6 22 31 59

Chi square test was applied in which P value was 0.9579

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Table No. 8:- Stratifications Of Efficacy Of Induction Chemotherapy W.R.T Gender Distribution (n=59).
EFFICACY Male Female Total
Effective 28 14 42
Not effective 12 5 17
Total 40 19 59

Chi square test was applied in which P value was 0.7703

Table No. 9:- Stratifications Of Efficacy Of Induction Chemotherapy W.R.T Stage Of Carcinoma.(n=59)
EFFICACY Stage III Stage IVA Stage IVB Total
Effective 16 23 3 42
Not effective 6 9 2 17
Total 22 32 5 59

Chi square test was applied in which P value was 0.8445

Limitations
1. Sample Size: The study involved a relatively small number of patients, which may limit the generalizability of
the findings to a wider population.
2. Short Follow-Up Period: The follow-up duration was limited, preventing assessment of long-term efficacy and
survival rates.
3. Observational Data: The study's reliance on observational data may introduce biases, such as selection bias
and reporting bias.

Conflict of Interest Statement

The authors declare that there is no conflict of interest regarding the publication of this paper. There are no financial
or personal relationships with other individuals or organizations that could inappropriately influence or bias the
content and findings of this work. This disclosure aims to uphold the integrity of the scientific record, ensuring that
all decisions and interpretations of the research are free from any undue influence.

Source of Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit
sector.

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