Journal of the Egyptian Nat. Cancer Inst., Vol. 18, No.
4, December: 348-356, 2006
Induction Chemotherapy with Paclitaxel and Cisplatin, Followed
by Concomitant Cisplatin and Radiotherapy for the Treatment
of Locally Advanced Nasopharyngeal Carcinoma
EHAB MOSTAFA, M.D.*; MOHAMED N. NASAR, M.D.**; NABIL A. RABIE, M.D.;
SAMER A. IBRAHIM, M.D.; HAMMAD M. BARAKAT, M.D.** and AMRO N. RABIE, M.D.**
The Departments of Radiation Oncology* & Nuclear Medicine, Faculty of Medicine, Ain Shams University &
Sohag Cancer Center and Otolaryngology**, Faculty of Medicine, Ain Shams University, Cairo.
ABSTRACT
Purpose: To evaluate the efficacy and outcome of
neoadjuvant paclitaxel and cisplatin chemotherapy fol-
lowed by concurrent cisplatin and irradiation in patients
with locally advanced nasopharyngeal (NP) squamous
cell carcinoma.
Patients and Methods: The trial included 36 patients
with locally advanced nasopharyngeal squamous carcinoma
presented to Radiation Oncology and Otolaryngology
departments - Ain Shams university hospitals, and Sohag
Cancer Center between November 2002 and March 2006.
Eligible patients were treated first with three cycles of
induction chemotherapy (IC), paclitaxel (175mg/m2 on
day 1) and cisplatin (80mg/m 2 on day 1) followed by
concomitant conventionally fractionated radiation (70Gy
in 2Gy fractions) and cisplatin 20-mg/m2/day on days 1-
5, 22-26 and 43-47 of the radiation therapy.
Results: Twenty nine patients (80%) and 32 patients
(89%) achieved objective response after IC and concom-
itant chemoradiation (CCRT) respectively. The actuarial
3 years survival was 68%, and the actuarial 3 year pro-
gression free survival (PFS) was 66%. Survival and PFS
were significantly better for patients with smaller tumor
volume (stage III), compared with patients with stage IV.
Thirteen patients (36%) have elements of local and/or
regional failure and 5 patients (14%) have an element of
distant metastasis. Neutropenia (25%), mucositis (22%)
and vomiting (20%) were the most severe toxicities re-
corded (grade 3 and 4) during IC while mucositis (36%),
dermatitis (28%), anemia (14%) and vomiting (14%) were
the most pronouncing toxicities (grade 3 and 4) during
CCRT.
Conclusions: IC followed by CCRT treatment program
is feasible, tolerable and safe. This strategy improved
Corresponding author: Ehab Mostafa
Tel.: 00967-733505714.
E-mail address: ehmostafa@hotmail.com,
Oncology1.san@sghgroup.net
348
local control and distant disease control. However com-
bined treatment program have failed to improve survival
rates over the historical result of CCRT trials.
Key Words: Nasopharynx Radiation Paclitaxel
Cisplatin.
INTRODUCTION
For many decades, radiotherapy was the
standard treatment for locally advanced nasopha-
ryngeal carcinoma (NPC) with local recurrence,
distant metastasis and 5-year survival rates of
15%-50%, 20%-40% and 24%-52% respectively
[1-3]. The Intergroup 0099 study (IGS) was the
first to show a survival benefit with chemorad-
iation in locally advanced NPC which compared
radiation therapy alone with cisplatin based
concomitant chemoradiation (CCRT) and adju-
vant chemotherapy [1]. Overwhelming evidences
from randomized studies and recent systematic
meta-analysis now support the use of concurrent
cisplatin based CCRT as the standard of care
for treatment of locally advanced NPC [4-8].
However, the prognosis still remains poor with
CCRT because it is technically difficult to irra-
diate the whole tumor target to cancericidal
dose without exceeding the tolerance of critical
structures especially for tumors with parapha-
ryngeal or intracranial extensions (T4) or those
with high N stage (N2-3). In addition, despite
the use of chemoradiotherapy, distant metastases
remain the predominant site of treatment failure.
Distant metastasis rate was as high as 36% [9-
11]. Studies trying to improve the results through
the addition of adjuvant or neoadjuvant chemo-
therapy to chemoradiotherapy are ongoing.
Induction Chemotherapy with Paclitaxel & Cisplatin
Patient tolerance to adjuvant chemotherapy is
limited by the cumulative toxic effects of con-
current chemoradiotherapy [1,12-16]. The poor
compliance with adjuvant chemotherapy after
concurrent chemoradiation can be overcome by
the use of neoadjuvant chemotherapy.
Building upon these informations, we con-
ducted this phase II study in which induction
chemotherapy (IC), paclitaxel and cisplatin
followed by concomitant chemoradiation
(CCRT) was used in an effort to eradicate mi-
crometastases, while still providing adequate
local control. Paclitaxel was selected for induc-
tion therapy with cisplatin as it was proved to
be an active drug in NPC [17]. The primary end
point of the study was locoregional control,
survival, and progression free survival (PFS),
and distant metastasis. The second end point of
the study was toxicity.
PATIENTS AND METHODS
This trial included 36 patients with locally
advanced nasopharyngeal squamous carcinoma
presented to Radiation Oncology and Otolaryn-
gology departments - Ain Shams university
hospitals, and Sohag Cancer Center between
November 2002 and March 2006.
Pretreatment evaluation:
Initial evaluation included: History, and
physical examination, complete blood count,
serum chemistries, chest X-ray and baseline
audiometery. Local and regional tumor extents
were assessed by computerized tomographic
scan (CT scan), and/or magnetic resonance
imaging (MRI), and fiberoptic examination of
the upper aero-digestive tract including the
nasopharynx, oropharynx, hypopharynx and
larynx.
Eligibility:
Eligible patients were above 18 years old
but not more than 70 years old with biopsy
proven WHO NPC, of stage III or IV disease
according to AJCC/UICC 1997 staging system
[18]. Other eligibility criteria were ECOG per-
formance status (PS) of 2, absolute neutrophil
count (ANC) 1500/uL, platelets 100,000/uL,
hemoglobin 10gm% creatinine clearance
(CrCl) 60mL/min, bilirubin <2mg/dL, and
transaminases levels < three times the upper
normal limit, no evidence of distant metastasis,
prior malignancy, prior chemotherapy or radio-
349
therapy to the head and neck region. Dental
extraction deemed necessary were performed
before radiation therapy. Each patient gave
written informed consent before entering the
study.
Treatment plan:
Induction chemotherapy: Consisted of 2
cycles of paclitaxel (175mg/m2 on day 1) fol-
lowed by cisplatin (80mg/m 2 on day 1), one
cycle every 3 weeks. Those who achieved at
least clinical and radiological partial response
to chemotherapy received an additional cycle
of chemotherapy. Thirty minutes prior to pacli-
taxel administration, all patients should receive
the following intravenous premedications: 20mg
dexamethazone, 50mg diphenhydramine and
300mg cimetidine. Cisplatin was given intrave-
nously, with standard pre and post-treatment
hydration. Cisplatin was given during a 2-hour-
period of forced hydration. Dexamethazone was
also administered intravenously or orally at a
dose of 4mg/6 hours until the following morn-
ing. Antiemetic included ondansetron or gran-
isetron IV during a period of 30 minutes before
starting chemotherapy was effective in control-
ling emesis.
Dose modification for Toxicity:
A new cycle of chemotherapy was postponed
until recovery if ANC was <1500/uL and platelet
count was <100,000/uL, then a 25% dose re-
duction in subsequent cycles of paclitaxel and
cisplatin in case of grade 3-4 neutropenia and/or
thrombocytopenia developed. For patients with
Cr Cl between 40 to 60mL/min, carboplatin
targeting an area under the curve of 5 (Calvert
formula) was to be substituted for cisplatin. If
the nadir of the Cr Cl was <40mL/min or the
patient developed otologic grade 3 or worse
toxicity, cisplatin was stopped totally. IC was
discontinued permanently in case of grade 2
neurologic toxicity. In case of symptomatic
arrhythmia or AV block, paclitaxel infusion was
stopped.
Concomitant chemoradiotherapy:
Radiation treatment was planned to begin 3
weeks after the last cycle of chemotherapy.
Radiation therapy was administered with Cobalt-
60 machine or 6-MV linear accelerator. The
patients were treated in supine position with
hyperextended neck. The patients head was
fixed using special fixing device or face mask.
350
The patients were treated through 2 parallel
opposing field and lower neck field. Two lateral
opposed fields were used to treat the nasophar-
ynx and adjacent structures and the upper neck
lymph nodes. The upper border of the fields
split the pituitary fossa. In case of base of skull
involvement, the upper border was at least 1cm
higher. The anterior border encompassed the
posterior 2cm of the nasal cavity and maxillary
antrum; in case of anterior extension, the border
was moved forward 2cm to cover the ethmoid
and maxillary sinus with adequate margin. The
posterior border was set behind the spinous
process of C2 vertebra The lower border of the
field was placed at the level of thyroid notch
or as low as the shoulder can permit. Dose was
specified at the central axis on the midplane.
The lower cervical lymph nodes and the supra-
clavicular lymph nodes were treated through
an anterior lower neck field at 3-cm depth. The
inferior border of the anterior field was 1cm
below the clavicles with shielding of lung apex.
The lower anterior neck field matched the lateral
fields on the skin by separating the two fields
by 1/2cm to avoid the overlap on the spinal cord
at the junction of the fields. The lateral border
was placed at the junction of medial two thirds
and the lateral third of clavicle.
The basic treatment was given as 2Gy /
fraction, once a day; 5 days/week to a total dose
of 50Gy in 25 fractions. At 46Gy, the lateral
fields were reduced to spare the spinal cord.
The posterior neck was supplemented with
either posterior electron beam (9-12MeV) field,
or in case of Cobalt-60 machine, with oblique
off cord boost fields. Clinically and radiologi-
cally negative neck and supraclavicular lymph
nodes received a total dose of 50Gy. An addi-
tional 20Gy/2Gy/fraction were given to reduced
volumes encompassing the nasopharynx, tumor
extensions and clinically/radiologically positive
nodes based on the pretreatment CT scan using
shrinkage field technique. To supplement the
dose to the clinically positive posterior neck
nodes, boost techniques using electron beam
(9-12MeV) were used. Residual resectable cer-
vical lymph nodes can be removed through neck
dissection, 4 weeks after radiation.
During radiation, cisplatin was given intra-
venously in a dose of 20-mg/m2/day from days
1-5, days 22-26 and days 43-47 of the radiation
therapy days. The chemotherapy was given at
Ehab Mostafa, et al.
approximately 60 minutes before receiving
radiotherapy. If carboplatin needed to be sub-
stituted for cisplatin, during radiation, the dose
was to target an area under the curve of 4 ac-
cording to the Calvert formula, divided into
five equal doses.
Follow-up:
The patients were evaluated by complete
physical examination before each cycle of IC.
Any clinical evidence of disease progression
during IC should be confirmed by CT scan and
fiberoptic nasopharyngoscopy. CT scan and
fiberoptic nasopharyngoscopy were done two
weeks after the second cycle of IC and two
months after completion of CCRT for assess-
ment of tumor response. Subsequent clinical
follow-up was 3 monthly in the first 2 years,
then 6 monthly afterwards. CT scan and Na-
sopharyngoscopy with biopsy were performed
whenever persistent disease or local recurrence
was suspected during follow-up period. Chest
X-ray was annually performed or when it was
clinically indicated.
Toxicity evaluation:
IC related toxicities were recorded according
to the National Cancer Institute Common Tox-
icity Criteria version 2.0 [19]. Acute and chronic
radiation related toxicities were graded accord-
ing to the acute and chronic Radiation Morbidity
Scoring Criteria of the Radiation Therapy
Oncology Group (RTOG) [20].
Tumor response:
Tumor response was defined according to
the WHO criteria [21].
Survival and patterns of failure:
Survival was estimated from the date of first
treatment day to death or last follow-up visit.
PFS was estimated from the date of first treat-
ment day to first evidence of disease progres-
sion. Early failure means failure to achieve local
and/or regional control at the first time of as-
sessment after chemoradiation. Delayed failure
means failure during the course of follow-up.
Patients who rendered in complete response
after neck dissection was considered disease
free unless they developed delayed failure during
follow-up.
Induction Chemotherapy with Paclitaxel & Cisplatin 351

RESULTS B- Concomitant chemoradiation:

The demographic baseline patients, and
disease characteristics of the 36 eligible patients
with locally advanced NPC including age, sex,
performance status, WHO classification and
AJCC/UICC staging are detailed in Table (1).
Treatment compliance and toxicity:
A- Induction chemotherapy:
Twenty nine patients (80%) received 3 cycles
of IC, of which two patients shifted to paclitaxel
/carboplatin because of low level of creatinine
clearance after the second cycle of chemother-
apy. Seven patients received only 2 cycles of
chemotherapy because they have either stable
or progressive disease. Nine patients (25%)
have a 25% reduction of chemotherapy doses
in subsequent cycles because of developing G
3/4 neutropenia or thrombocytopenia. Three
patients (8%) developed grade 2 peripheral
neuropathy after the third cycle. Fourteen pa-
tients (42%) developed at least one grade 3 or
4 toxicity. Grade 3/4 neutropenia, mucositis
and vomiting, the most pronouncing toxicities
during IC were recorded in 25%, 22% and 20%
of patients respectively (Table 2).
Table (1): Patients and disease characteristics.
Out of thirty six patients, twenty patients (56%)
completed 3 cycles of cisplatin during radiation,
and 11 patients (31%) received 2 cycles of che-
motherapy and the remaining five patients received
only one cycle of chemotherapy because of treat-
ment intolerability. Five patients (14%) received
carboplatin instead of cisplatin, 2 because of
peripheral neuropathy and 3 patients because of
low Cr Cl. Thirty two patients (89%) completed
successfully the basic course of external irradiation
and 4 patients received suboptimal doses (46, 52,
60 and 60Gy respectively) because of disease
progression in two patients and treatment intoler-
ability in the remaining 2 patients. The median
overall treatment time for radiotherapy was 52
days (range from 40 days to 62 days). Twenty one
patients (58%) developed at least one grade 3 or
4 toxicity. Grade 3 and 4 mucositis, dermatitis,
anemia and vomiting, the most severe toxicities
during CCRT, were developed in 36%, 28%, 14%
and 14% of patients respectively (Table 2). No
serious late radiation effects such as blindness,
myelopathy or soft tissue necrosis have occurred.
All the patients have variable degree of submental
edema. Twelve patients (33%) have grade 3 chron-
ic xerostomia. Two patients (6%) have clinical
hypothyroidism. Five patients (14%) experienced
hearing impairment during follow-up.

No. of patients 36 Response:

After 2 cycles of IC, 29 patients (80%)
Age (years):
Mean SD 44.321.3
achieved objective response [CR in 7 patients
(19%) and PR in 22 patients (61%)]. Five patients
Sex: (14%) have stable disease and two patients (6%)
Male/Female 22/14
have progressive disease. At the end of treatment,
ECOG Performance status: 32 patients (89%) achieved objective response
0 24 (66%) [CR in 25 patients (70%) and PR in 7 patients
1 9 (25%)
2 3 (9%) (19%)]. Of the 7 patients who have partial re-
sponse; three have only residual neck disease that
WHO Classification: mandated neck dissection to render disease free,
Type I 3 (9%)
Type II 8 (22%) and three patients have residual disease in the
Type III 25 (69%) nasopharynx that proved positive by biopsy, and
one patient have residual nasopharyngeal and
Tumor (T):
T2 3 (8%) neck disease. This means that 28 patients (78%)
T3 13 (36%) rendered disease free after chemoradiation and
T4 20 (56%) neck dissection. Four patients failed to achieve
Lymph node (N): objective response at the end of treatment (2 have
N1 5 (14%) stable and 2 have progressive disease). Of interest,
N2 19 (53%) 8 patients failed to achieve complete response at
N3 12 (33%) the nasopharynx, 7 patients had originally T4
AJCC/UICC staging system: disease and one patient had originally T3 disease.
Stage III 14 (39%) Table (3) shows the clinical response after induc-
Stage IV 22 (61%) tion chemotherapy and at the end of treatment.
352 Ehab Mostafa, et al.

Table (2): Acute toxicity (grade 3 and 4) during induction chemotherapy (IC) and concomitant chemoradiation (CCRT).

IC CCRT
Toxicity
Grade 3 Grade 4 Total Grade 3 Grade 4 Total

Anemia 2 (6%) 0 2 (6%) 5 (14%) 0 5 (14%)

Neutropenia 6 (17%) 3 (8%) 9 (25%) 2 (6%) 0 2 (6%)
Thrombocytopenia 2 (6%) 0 2 (6%) 0 0 0
Mucositis 8 (22%) 0 8 (22%) 13 (36%) 0 13 (36%)
Vomiting 5 (14%) 2 (6%) 7 (20%) 4 (11%) 1 (3%) 5 (14%)
Dermatitis 0 0 0 10 (28%) 0 10 (28%)
Otitis externa 0 0 0 3 (8%) 0 3 (8%)

Table (3): Clinical response after induction chemotherapy and at the end of treatment.

After Induction After Concomitant

Response chemotherapy chemoradiation

No. (%) No. (%)

Complete Response (CR) 7/36 (19%) 25/36 (70%)

Partial Response (PR) 22/36 (61%) 7/36 (19%)
Stable Disease (SD) 5/36 (14%) 2/36 (6%)
Progressive Disease (PD) 2/36 (6%) 2/36 (6%)
Objective response according to the site: Nasopharynx vs. Lymph nodes
Nasopharynx, by endoscopy & CT:
Complete Response (CR) 7/36 (19%) 28/36 (78%)
Partial Response (PR) 22/36 (61%) 4 /36 (11%)
Regional lymph nodes, by CT:
Complete Response (CR) 10/36 (28%) 28/36 (78%)
Partial Response (PR) 19/36 (52%) 4/36 (11%)*
* Three patients rendered disease free after neck dissection.

A correlation between the complete response
(25 patients) achieved at the end of treatment and
the different prognostic factors (Table 4) revealed
that there was a tendency for better results for
patients with smaller tumor volume (stage III),
WHO type III pathology, and good performance
status (0&1). However, the differences were sta-
tistically insignificant.
Survival and progression free survival:
The median follow-up duration was 34 months
(range from 7 to 48 months). The actuarial 3 years
survival was 68%, [95% CI 53% & 84%]. The
actuarial 3 year PFS was 66%, [95% CI 50% &
82%] (Fig. 1). A correlation between the survival
and PFS and the different prognostic factors re-
vealed that survival and PFS were significantly
better only for patients with smaller tumor volume
(stage III), compared with patients with stage IV
(p=0.001) (Fig. 2A,B).
Pattern of treatment failure:
The details of patterns of failure were shown
in Table (5). A total of 15 patients (41%) have
treatment failure, 11 patients (30%) have an early
failure, three of them have residual neck disease
at the completion of the treatment and rendered
disease free after neck dissection, and 4 patients
(11%) have delayed failure. Thirteen patients
(36%) have elements of local and/or regional
failure and 5 patients (14%) have an element of
distant metastasis.
Induction Chemotherapy with Paclitaxel & Cisplatin 353

Table (4): Prognostic factors in relation to complete 100

response at the end of treatment. Stage III (n=14)
Objective response 80
Category p-value

Percent surviving
No. (%)
60
Age:
30 (6) 3/6 (50%)
40
>30 (30) 22/30 (73%) 0.3
Stage IV (n=22)
Sex:
20
Males (22) 16/22 (72%)
p=<0.001
Females (14) 9/14 (64%) 0.7
0
Stage: 0 6 12 18 24 30 36 42 48
III (14) 11/14 (79%)
IV (22) 14/22 (64%) 0.2 Time (months)

WHO Type: Fig. (2-A): Survival in relation to TNM stage.

I/II (11) 6/11 (55%)
III (25) 19/25 (76%) 0.2
100 Stage III (n=14)
Performance status:
0&1 (33) 24/33 (73%)
80
2 (3) 1/3 (33%) 0.4
Percent surviving

60
Table (5): Pattern of treatment failure.
40
Failure No. (%) Stage IV (n=22)

Local failure only 3 (8%) 20

p=0.001
Regional failure only 3 (8%)*
0
Locoregional failure only 4 (11%) 0 6 12 18 24 30 36 42 48
Time (months)
Distant metastasis only 2 (6%)
Fig. (2-B): PFS in relation to TNM stage.
Distant metastasis + local/regional failure 3 (8%)
* Those patients rendered disease free after neck dissection. DISCUSSION
NPC is distinguished by relative radiosensi-
100 tivity and chemosensitivity. Several phase II
trials of IC followed by cisplatin based-CCRT
have been published with promising results [22-
80
Overall survival 29]. Various cisplatin based chemotherapeutic
Percent surviving

regimens have been utilized for induction ther-

60 apy e.g. cisplatin, epirubicin, and continuous
infusional fluorouracil (ECF) [22] , cisplatin,
40 fluorouracil, leucovorin and interferon- 2b
Progression free [23], carboplatin and paclitaxel [24], Cisplatin
survival
20 and 5 FU [25,26] cisplatin, epirubicin, and pacli-
taxel [27], cisplatin and epirubicin [28] and cis-
0
platin and gemcitabine [29].
0 6 12 18 24 30 36 42 48
In the present study, all the patients have
Time (months) high risk locally advanced disease, 56% have
Fig. (1): Actuarial 3-year survival and progression free T4 disease and 86% have N2/3 disease. The
survival. objective response rate was 80% after IC (CR
354
19% and PR 61%). After CCRT and neck dis-
section, CR rate was achieved in 78% of the
patients. These results compared favorably to
the results reported by other similarly designed
phase II trials [22,26-28] . In these trials, the
objective response rate after IC was achieved
in 79%-86% of patients (CR from 6%-15%)
and at the end of the treatment, CR rate ranged
from 56% to 80%. However, other investigators
reported objective response rate ranging from
>90% to 100% after IC and at the end of treat-
ment [23,29,30]. The drawback in these studies
was that only clinical and endoscopic examina-
tions were used to assess response after IC; the
inclusion of radiologic imaging would give a
more accurate and comprehensive assessment.
In the International Nasopharyngeal Carcinoma
Study Group [30] locally advanced NP patients
were treated with the combination of cisplatin,
epirubicin, and continuous infusion of bleomy-
cin (BEP). Those patients achieved a complete
response rate of 47% after IC. The BEP regimen
was accompanied by excessive toxicity and 8%
treatment related mortality rate. In addition, the
response in this trial was reported based on
clinical assessment without any imaging assess-
ments. The relatively high locoregional control
rate at the end of treatment, in different trials,
may be attributed to the greater cytoreduction
before starting radiation as a result of better
drug delivery to the tumor with still intact
vasculature during IC. In addition, 8 patients,
in the present study, failed to achieve complete
response at the nasopharynx, 7 patients had
originally T4 disease and one patient had orig-
inally T3 disease. We believed that, the results
can be improved more in the future with the
different boost techniques using brachytherapy,
3D conformal irradiation or IMRT which pro-
vide dose escalation with better dose differen-
tiation between tumor and normal tissues
[9,31,32].
The actuarial 3 years survival and PFS, in
the present study, were 68% and 66% respec-
tively. Survival and PFS were significantly
better for patients with smaller tumor volume
(stage III), compared with patients with stage
IV. Our results compared favorably to other
phase II similarly designed studies [25-29]. In
contrary, Rischin et al. [22] reported an excellent
4-year overall survival of 90% and the 4-year
PFS rate was 81%. However, in Rischin et al.
trial, only 40% of patients were of stage IV
Ehab Mostafa, et al.
according to the new staging (UICC criteria,
ed. 5, 1997). The study by Lin et al. [6] using
concurrent cisplatin plus 5-FU and radiation
achieved significant benefit in both PFS and
overall survival over radiation alone. The mag-
nitude of gain in the 5-year overall survival rate
amounted to 18% (72% Vs. 54%). However,
only 29% of patients have stage IV disease
according to (UICC criteria, ed 5, 1997). The
trial by Chan et al. [7] using concurrent cisplatin
and radiation showed that the gain in 5-year
PFS was 8% (60% Vs. 52%) and the gain in
overall survival was 11% (70% Vs. 59%). How-
ever, in Chan et al., trial, only 29% of patients
have T3/T4 disease, and 26% have stage II
disease in chemoradiation arm.
The primary rationale for IC in nasopharyn-
geal cancer has been to decrease the risk of
developing distant metastases. Five patients
(14%) have an element of distant metastasis.
In CCRT trials, despite achievement of excellent
locoregional control, the incidence of distant
metastasis remained as high as 36% [6,7,9-11].
The higher incidence of distant metastasis in
CCRT strategy may be explained by the fact
that systemic levels of the drugs, which were
usually suboptimal, during radiation, were not
sufficient to control micrometastatic disease.
Improved control of distant disease could be
achieved by eradicating micrometastatic disease
through systemic drug delivery before the local
treatment.
The induction therapy and chemoradiation
were well tolerated as 80% of patients completed
3 cycles of IC. The IC did not interfere with
the delivery of subsequent treatment as 87% of
patients completed successfully the basic course
of external irradiation concomitant with at least
2 cycles of chemotherapy. One advantage of
induction compared with adjuvant chemotherapy
is the greater ability to administer full-dose
chemotherapy as planned. In the present trial,
only 9 patients have 25% reduction of chemo-
therapy dose because of G3/4 toxicity. In IGS
trial [1], only 55% of patients received all three
planned cycles of adjuvant chemotherapy and
33% did not receive any adjuvant chemoradio-
therapy. Of major concern in our study was the
incidence of peripheral neuropathy because of
the overlapping toxicities between paclitaxel
and cisplatin, 3 patients (8%) developed grade
2 peripheral neuropathy after the third cycle
which was compared favorably to other studies
Induction Chemotherapy with Paclitaxel & Cisplatin
utilizing platinum compounds and taxanes.
Fountzilas et al. [27] recorded 13% incidence
of grade 1/2 peripheral neuropathy after IC of
cisplatin, epirubicin and paclitaxel. During
CCRT, we preferred to use cisplatin 20mg/
m2/day over 5 days because high-dose cisplatin
(100mg/m2 on one day every 3 weeks) infusion
often causes severe emesis with subsequent
treatment interruption. The IC did not add to
the morbidity of subsequent chemoradiation.
Lin et al. [6] reported in their randomized trial,
45% and 30.5% incidence of G3/4 mucositis
and dermatitis respectively in the chemoradia-
tion group. This better treatment tolerability
can be explained by the fact that nutrition and
nitrogen balance could be improved in these
patients due to cytoreduction induced after IC
which may ameliorate the severity of acute
toxicity during CCRT.
Conclusions: IC followed by CCRT treat-
ment program is feasible, tolerable and safe.
This strategy improved local control and distant
disease control. Although this combined treat-
ment program have failed to improve survival
rates over the historical result of CCRT trials,
randomized trials on a larger number of patients
with longer follow-up are required before getting
solid conclusions.
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