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175]
ORIGINAL ARTICLE Head and Neck Cancer
Role of neoadjuvant chemotherapy in advanced carcinoma of the hypopharynx
and larynx
Poonam Joshi, Amit Joshi,Vanita Norohna, Pankaj Chaturvedi,Vijay Patil, Jai Prakash Agarwal, Shashikant Juvekar,
Kumar Prabhash

Abstract
Background: To assess the response rate and impact of neoadjuvant chemotherapy (NACT) in advanced carcinoma of the hypopharynx and larynx.
Materials and Methods: This is a retrospective case series of 80 patients with locally advanced laryngopharynx carcinoma who received NACT from April
2010 to October 2011 at our tertiary care center.The patients received NACT either for achieving resectability or for organ preservation. Results: Majority
of the patients (60%) had T4 a disease. Grade 3 and 4 neutropenia was seen in 18%, febrile neutropenia in 4%, mucositis in 4%, diarrhea in 5%, and vomiting
in 3% patients. Resectability could be achieved in 34%, and larynx was preserved in 51% patients at a mean follow‑up of 13 months. Conclusions: NACT
was safe with acceptable toxicity. Majority of the patients who achieved resectability had oropharyngeal involvement. NACT followed by concurrent
chemoradiotherapy could provide a high rate of organ preservation.
Key words: Advanced carcinoma, hypopharynx, larynx, neoadjuvant chemotherapy

Introduction Of the total 99  patients who were treated, 80  patients were
Concurrent chemoradiotherapy is the treatment of choice eligible for analysis as complete clinical data was available in
for locally advanced laryngeal‑hypo pharyngeal cancers for these 80  patients. Twelve patients started chemotherapy at our
organ preservation.[1‑4] Surgery remains the choice of treatment hospital but did not complete treatment due to logistic reasons
in locally advanced laryngeal‑hypopharngeal malignancies and took treatment at their local place, details of which are not
when organ preservation is not feasible. However, treatment available. Rest 7  patients, did not come for a single follow‑up
guidelines fail to define borderline resectable T4 lesions which postdefinitive treatment, and no further details about them were
may not be amenable for surgical excision. These include available. Hence, they were excluded from the study.
advanced laryngeal or hypopharngeal tumors with either of the A complete medical history of the patients was obtained.
below mention criteria: Complete preoperative evaluation was done in all patients
1. Exolaryngeal spread either via the laryngeal membranes including a direct laryngoscopy, imaging with contrast enhanced
without cartilage erosion or through cricothyroid space computed tomography  (CT) scans, magnetic resonance imaging,
2. Extension to oropharynx or with the involvement of or positron emission tomography scans whenever indicated.
prevertebral fascia or parapharyngeal space. NACT was given either as two‑drug (platinum  +  taxane) or
three‑drug combination (platinum  +  taxane  +  5 fluorouracil
Surgery in such situations often leads to positive margins [5FU]). These patients were not suitable for definitive treatment
and the morbidity of extensive surgery is unacceptably at presentation due to advanced disease.
high. In cases of bulky N3 nodes treated with concurrent These patients were divided into two groups depending
chemoradiotherapy, response rates are poor. [5] Neoadjuvant upon the intent of giving NACT:  (a) Group  1  (35/80)  ‑  The
chemotherapy  (NACT) is also one of the modality of treatment intent of giving NACT was to achieve resectability. Patients
recommended by NCCN for advanced laryngeal‑hypopharyngeal with extensive soft tissue/skin involvement, Oro‑pharyngeal
cancers. The hypothesis of the present study is that NACT involvement, cartilage erosion with extensive soft tissue disease
may be useful in selecting patients for appropriate definitive were included. These patients had gross cartilage erosion,
treatment depending upon the response to chemotherapy. exolaryngeal disease and nonfunctional larynx  (tracheostomized).
Materials and Methods Hence, these patients were considered for surgery. Patients with
This is a retrospective analysis of 80  patients with locally T4 disease and nonfunctional larynx undergo standard surgery
advanced carcinoma of the hypopharynx and larynx, who at our center. (b) Group  2  (45/80)  ‑ The intent of giving NACT
received NACT from April 2010 to October 2011 at our tertiary was to achieve Organ preservation. Patients with bulky disease,
care center. The medical details of these patients were retrieved inner cartilage erosion, exolaryngeal disease without cartilage
from medical records of the hospital. Cases were selected erosion, N3 nodes or nodes with restricted mobility/skin
based on the following eligibility criteria:  (1) Biopsy confirmed involvement were included.
squamous cell carcinoma of the hypopharynx and larynx  (2) all The primary objectives of the study were resectability and
these patients were treatment Naïve at presentation,  (3) patients organ preservation.
with bulky T3 disease or with inner cartilage erosion/T4 disease Secondary objectives were response rate of tumor to NACT,
with extensive soft tissue involvement, and  (4) patients with N3 side effects, progression‑free survival, overall survival.
nodes or nodes with restricted mobility or skin involvement. Resectability was defined as tumors in which adequate margins
This is an open access article distributed under the terms of the Creative Commons
Access this article online Department of Medical Oncology,Tata memorial Hospital, Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix,
Quick Response Code:
Mumbai, Maharashtra, India tweak, and build upon the work non‑commercially, as long as the author is credited
Correspondence to: Dr. Kumar Prabhash, and the new creations are licensed under the identical terms.
E‑mail: kprabhash1@gmail.com
For reprints contact: reprints@medknow.com

How to cite this article: Joshi P, Joshi A, Norohna V, Chaturvedi P, Patil V,

Website: www.sajc.org Agarwal JP, et al. Role of neoadjuvant chemotherapy in advanced carcinoma of
DOI: 10.4103/2278-330X.202557 the hypopharynx and larynx. South Asian J Cancer 2017;6:15-9.

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Joshi, et al.: Chemotherapy in cancers of the laryngopharynx

could be achieved post‑NACT. Organ preservation was defined were T4a, and 6% were T4b. The tumor, nodal status and
as the treatment with chemoradiotherapy with preservation of stage of the disease and Eastern Cooperative Oncology Group
larynx. scale are described in Table  1. The median hemoglobin of the
NACT was given as two or three drug as 3  weekly regimen population was 12.35  g/dl  (8.9–17.2  g/dl), and median albumin
with cisplatin and docetaxel as 75  mg/m2 each on day 1 and was 4  mg/dl  (2.7–4.7  mg/dl).
5‑flurouracil as 750  mg/m2 as 24  h intravenous  (IV) infusion Patients were given NACT due to various reasons as shown
for 5  days for three cycles. Patients receiving three‑drug in Table  2. Sixty‑seven patients received two cycles of
regimens were given granulocyte‑colony stimulating factor chemotherapy, and 13  patients received three cycles. Sixty
prophylactically from day 6 to 12. Tablet levofloxacin patients received two drug regimen and 20 received three‑drug
500  mg once daily was given for same duration as a primary regimen. Either docetaxel or paclitaxel was used  [Table  3].
prophylaxis for bacterial infections. Carboplatin as AUC 6 Response to NACT and suitability for resectability or organ
was given to older individuals or those with compromised preservation were assessed at the completion of two cycles of
glomerulo‑filtration rate of  <60  ml/min. NACT in the two groups. The overall response rate  (complete
All patients received standard prophylactic 5‑HT 3 response  [CR] + partial response  [PR]) was 58% with 5% CR
antagonists  (ondansetron/granisetron). Patients receiving and 53% PR rate. Thirty‑seven patients had stable disease, and
cisplatin, in addition, received neurokinin 1 receptor 5% had PD. The response assessment when done separately for
antagonist aprepitant for delayed emesis. All patients primary and nodes was 71% and 59%, respectively.
received premedication for taxanes in the form of H2 The Grade  3 and 4 toxicities of NACT were neutropenia in
blockers  (ranitidine), antihistaminics  (phenargan), and 18%, febrile neutropenia in 4%, mucositis in 4%, diarrhea
dexamethasone. Patients who completed two cycles of NACT
were included in the study. Table 1: Demographic details (n=80)
In majority of patients, two drugs were used due to logistic Age Variables Age in years
reasons and economic constraints. Poor performance Age  (years)
status and low creatinine clearance were other reasons. Mean 54
Cisplatin/carboplatin +  docetaxel/paclitaxel were used in two drug Median 54
regimen, and 5FU was used in addition in three‑drug regimen. Range 22-80
Number of patients Percentage
Clinical response and toxicities were assessed on day 8 and 20 Sex
of the cycle. Post 2  cycles of NACT, patients were assessed Male 72 90
for further management in multidisciplinary joint clinic. Female 08 10
Response assessment was done with RECIST criteria 1.1. Site of the disease
All CT scans were evaluated by a senior radiologist pre‑  and Pyriform sinus 49 61
post‑NACT. Side effects were assessed with common toxicity Postcricoid 07 09
criteria version  4. Dose reduction was done for Grade  3 or 4 Posterior pharyngeal wall 03 04
toxicities. Patients with sufficient tumor shrinkage underwent Supraglottis 15 19
surgery in the first group. In the other group, where the intent Glottis 05 06
was organ preservation, patients were considered for concurrent Subglottis 01 01
chemoradiotherapy/radiotherapy. Tumor status
T1 01 01
Those patients who had progressive disease  (PD) were
T2 04 05
treated with palliative radiotherapy/chemotherapy or best
T3 22 28
supportive care. All patients were followed up till progression, T4a 48 60
recurrence or death whichever occurred first. Censoring of T4b 05 06
data was done on March 2013, and data were analyzed after Nodal status
updating the records through electronic medical records. N0 23 29
Tumor responses were assessed by clinical evaluation and N1 10 13
imaging studies done 12  weeks after the completion of N2a 10 12
chemoradiotherapy. Patients were monitored every 3  monthly N2b 15 19
for recurrence for first 2  years by clinical examination or N2c 09 11
imaging if required. In our study, the follow‑up varied from N3 13 16
2  months to 27  months. Staging
Stage III 06 07
Statistical analysis was done using the software SPSS Stage IVa 56 70
20.0  (IBM, NY, USA). Stage IVb 18 23
Calculation of values was done in percentages. Survival was ECOG performance status
calculated with Kaplan–Meier analysis [Figures 1-4]. 0 06 07
1 68 86
Results
2 06 07
The mean age of the population was 54  years (range ‑ 3 0 0
22–80  years). Pyriform sinus was involved in 61% and 4 0 0
supraglottic larynx in 19% patients. Sixty percent of the tumors ECOG=European Cooperative Oncology Group

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Joshi, et al.: Chemotherapy in cancers of the laryngopharynx

in 5%, and thrombocytopenia in 1% patients. Other side 29  patients received radical chemoradiotherapy and 10  patients
effects included nausea, anorexia, hiccough, renal dysfunction, received radical radiotherapy. One patient received only 40  Gy
hypokalemia, and hyponatremia. The toxicities are elaborately dose of radiotherapy as he developed trachea‑esophageal
described in Table  4. fistula. One received palliative radiation therapy due to the
Post‑NACT, 12  patients  (12/35) underwent radical treatment progression of nodal disease, and encasement of carotid artery
in the form of total laryngectomy or total laryngectomy with and one patient was considered for symptomatic care due to the
partial/total pharyngectomy in the first group. All patients had progression and fungation of nodal disease. One patient died
R0 resection. The margins were wide in 10  patients, close due to septicemia following febrile neutropenia post‑NACT.
in 2  patients. Four patients achieved complete pathological Two patients denied further treatment although, both had
response with NACT. achieved PR.
All 12  patients received adjuvant postoperative chemoradiation Salvage total laryngectomy was done for one patient who
or radiotherapy. Weekly cisplatin at a dose of 30  mg/m 2 had resectable residual disease at the primary site and neck
was given as an IV infusion for 1  h period for 6–7  weekly dissection in 1  patient, postradiotherapy.
doses during the course of radiotherapy. The definitive The larynx preservation rate was calculated for those patients
curative radiation dose administered to the primary tumor was only where the initial intent was organ preservation. Hence,
between 66 and 70  Gy, administered as fractions of 2  Gy/day larynxes were preserved in 51%  (23/45) patients and were
5  days/week. disease‑free after a mean follow‑up of 13  months.
Four patients received palliative radiotherapy and 1  patient The pattern of failure was mostly regional followed by local
symptomatic care in view of progressive, unresectable disease. recurrence. The patterns of failure, shown in Table  5, show the
Remaining 18  patients were discussed in joint clinic and were site of first failures. Four patients who did not receive definitive
given chemoradiotherapy or radiotherapy with mean dose of treatment post‑NACT were excluded from this analysis.
60–70  Gy. The median progression‑free survival  (PFS) in the first group
Following NACT, resectability was achieved in  (12/35) 34% where the intent of NACT was resectability was 20  months
patients. The reasons for achieving resectability were shrinkage and in those where the intent was organ preservation was
in tumor size, disappearance of diffuse edema/inflammation 19  months respectively. The mean overall survival was
of the overlying skin or soft tissues thus enabling resection 22  months, and median was not reached in both the groups.
with free margins. Majority of these patients had disease Discussion
extending to oropharynx  (50%, 6/12). Two patients developed
In view of the advanced stage at the time of presentation,
nonsalvageable recurrences, one locally and the other regionally
hypopharyngeal cancers carry a poor prognosis.[6‑10] NACT has
with distant metastasis. Eighty‑three percent  (10/12) patients in
been used advanced head and neck cancers with the aim of
this group were disease free at a mean follow‑up of 12  months.
organ preservation and for the achievement of resectability.[11,12]
In the other group, where the intent was organ preservation, Majority of international trials have used three‑drug TPF
regimen for induction.[13‑15] However, we have used a two‑drug
Table 2: Various reasons for giving neoadjuvant regimen of taxane and platinum in majority patients. The two
chemotherapy (%) drug regimen was found to be cheaper, easy to administer,
Reasons for NACT Number Percentage less toxic, and has reasonably good response. The response to
of patients of patients NACT was in accordance with the RECIST criteria 1.1. We
Oropharyngeal involvement 21 26
observed that taxanes have similar efficacy but lesser toxicity
N3 node/restricted mobility 13 16
as compared to conventional regimens of platin with FU.[16] In
Extensive exolaryngeal disease 11 14
with cartilage erosion our series, the overall response rate was 58%, including 5% CR
Exolaryngeal disease without 05 06 and 53% PR rate. TAX  324 reported 72% and 64% response
cartilage erosion rates with TPF and PF, respectively.[17] Toxicities were much
Extensive disease with doubtful 10 13 less in our series with Grade  3 or 4 neutropenia in 18% and
thyroid cartilage invasion thrombocytopenia in 1% patients, whereas in TAX  324 trial, the
Bulky/extensive disease 12 15 Grade  3 or 4 neutropenia was 83% in TPF and 56% in PF. The
Prevertebral muscle 03 04 Grade  3 or 4 thrombocytopenia was 11% and 4%, respectively.
involvement/abutment
This could be attributed to use of two drugs and two cycles of
Parapharyngeal/retropharyngeal 02 02
NACT in majority of the patients in our study.
spaces involvement
Carotid artery encasement 03 04 Although all patients had advanced stage disease, the two
NACT=Neoadjuvant chemotherapy groups were different. The first group had cartilage erosion,

Table 3: Chemotherapy drug regimen and number of cycles given

Number of Cisplatin + Cisplatin + Carboplatin Carboplatin Three‑drug regimen Total
cycles given docetaxel paclitaxel + docetaxel + paclitaxel docetaxel + cisplatin + 5FU
2  cycles 13 17 12 10 15 67
3  cycles 3 2 3 0 5 13
Total 60 20 80
5FU=5‑fluorouracil

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Joshi, et al.: Chemotherapy in cancers of the laryngopharynx

Figure  1: Kaplan–Meier curve Figure  2: Kaplan–Meier curve Figure  3: Kaplan–Meier curve Figure  4: Kaplan–Meier curve
showing overall survival in patients showing progression‑free survival showing overall survival in patients showing progression‑free survival
where the intent of neoadjuvant where the intent of neoadjuvant where the intent of neoadjuvant in patients where the intent of
chemotherapy was resectability chemotherapy was resectability chemotherapy was organ neoadjuvant chemotherapy was
preservation organ preservation

Table 4: Toxicities of neoadjuvant chemotherapy

Grade 1 Grade 2 Grade 3 Grade 4 None regimen in majority of the patients and retrospective nature of
Vomiting 18 48 03 0 31 the study. As data are sparse in literature about the management
Mucositis 19 33 02 04 42 of moderately and very advanced laryngopharyngeal cancers,
Diarrhea 17 31 03 02 47 this data will be a good guide for the clinicians in making
Neutropenia 06 15 24 21 34 decisions.
Febrile neutropenia 02 02 96 Conclusion
Thrombocytopenia 06 05 01 0 88
Peripheral neuropathy 03 02 0 0 95
NACT is a safe and feasible method with acceptable toxicity.
Hiccoughs 01 01 0 0 98 It can be used to achieve resectability in advanced cancers of
Renal dysfunction 05 03 03 0 89 the larynx and hypopharynx with oropharyngeal involvement.
Anorexia 08 12 3 0 77 NACT followed by concurrent chemoradiotherapy could provide
Nausea 02 04 01 0 93 a high rate of organ preservation in advanced cancers of larynx
Hypokalemia 18 03 14 03 62 and hypopharynx.
Hyponatremia 25 28 05 42 Financial support and sponsorship
Anemia 13 27 07 01 52 Nil.
Conflicts of interest
Table 5: Pattern of recurrence There are no conflicts of interest.
Site of recurrence Number Percentage
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(Letter to the editor continue from page 14...) Departments of Medical Oncology, 1Radiodiagnosis and 2Surgical Pathology,
Tata Memorial Center, Mumbai, Maharashtra, India
However, surgical procedures demands expertise and there are Correspondence to: Dr. Jyoti Bajpai,
significant morbidity and mortality risk; hence, these should E-mail: dr_jyotibajpai@yahoo.co.in
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Advanced techniques and advanced skills are mutually reinforcing,
and both are essential for correct diagnosis and management!
This is an open access article distributed under the terms of the Creative Commons
Financial support and sponsorship Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix,
Nil. tweak, and build upon the work non‑commercially, as long as the author is credited
and the new creations are licensed under the identical terms.
Conflicts of interest
There are no conflicts of interest. How to cite this article: Jyoti B, Bharat C, Ravi T, Subhash RK, Asawari P,
Sudeep G. Billiary obstruction in a metastatic tumor of the pancreas from
Bajpai Jyoti, Chauhan Bharat,Thippeswamy Ravi,
breast cancer. South Asian J Cancer 2017;6:10-9.
Ramani K. Subhash1, Patil Asawari2, Gupta Sudeep

Letter to the Editor metastatic pRCC who has an ongoing response to sunitinib for
Long‑term survival in a case of metastatic 58  months.
A 25‑year‑old Omani female presented in December 2009
papillary renal cell carcinoma
with right flank pain. There was no hematuria or systemic
DOI: 10.4103/2278-330X.202562 features, or family history of cancer. Clinically, she was in
Dear Editor, performance status  (PS) 1  (WHO). Laboratory investigations
The papillary subtype of renal cell carcinoma  (pRCC) has a were normal. CT scan of chest/abdomen [Figure  1] and MRI
poorer prognosis when compared to their more common clear of abdomen  revealed a 7.5  cm  ×  7.3  cm  ×  7.2  cm right renal
cell counterpart  RCC  (ccRCC). We wish to report a case of mass, without significant abdominal lymphadenopathy, a normal
(Continue on page 24...)
South Asian Journal of Cancer ♦ Volume 6 ♦ Issue 1♦ January–March 2017 19