Supplementary Appendix

This appendix has been provided by the authors to give readers additional information about their work.

Supplement to: Zhang Y, Chen L, Hu G-Q, et al. Gemcitabine and cisplatin induction chemotherapy in nasopha-
ryngeal carcinoma. N Engl J Med 2019;381:1124-35. DOI: 10.1056/NEJMoa1905287
Table of Contents

Dose modifications of chemotherapy and toxicity prevention ................................................... 3

Description of the guidelines for intensity-modulated radiation therapy (IMRT) in this trial ... 5
Definitions of the endpoints ....................................................................................................... 7
Per-protocol analysis .................................................................................................................. 8
Figure S1: Kaplan-Meier Analysis for Recurrence-free Survival (A), Overall Survival (B),
Distant Recurrence-free Survival (C) and Locoregional Recurrence-free Survival (D) in the
two treatment groups (Per Protocol Population). ................................................................. 10
Subgroup analysis ..................................................................................................................... 11
Figure S2: Forest plots of treatment effects on Recurrence-free Survival within subgroups.
.............................................................................................................................................. 12
Figure S3: Kaplan-Meier Analysis of Recurrence-free Survival in the two treatment groups
stratified by different T classifications: (A) T1-2, (B) T3, (C) T4. ...................................... 13
Figure S4: Kaplan-Meier Analysis of Recurrence-free Survival in the two treatment groups
stratified by different N classifications: (A) N1, (B) N2, (C) N3. ........................................ 14
Figure S5: Kaplan-Meier Analysis of Recurrence-free Survival in the two treatment groups
stratified by KPS: (A) KPS = 90-100, (B) KPS = 70- 80. .................................................... 15
Table S1: List of participating centers...................................................................................... 16
Table S2: Compliance to gemcitabine and cisplatin induction chemotherapy......................... 17
Table S3: Compliance to concurrent cisplatin chemotherapy and radiotherapy ...................... 18
Table S4: Adverse events, according to trial group and grade.* .............................................. 19
Table S5: Disease recurrence distribution in the two treatment groups. .................................. 20
Table S6: Salvage treatments after disease recurrence............................................................. 21
Table S7: Comparison of adverse events of concurrent chemoradiotherapy with induction GP
versus induction TPF ................................................................................................................ 22

2
Dose modifications of chemotherapy and toxicity prevention

Dose modifications of induction chemotherapy and concurrent chemotherapy were dependent on

the hematological and non-hematological toxicities from the previous cycle. Dose modifications of

gemcitabine were planned for grade 4 neutropenia and its complications (febrile neutropenia and

neutropenic infection), grade 3 thrombocytopenia, grade 2 pulmonary toxicity, and impaired liver

function. The gemcitabine dose was reduced by one level (200 mg/m2) for the first episode of the

above toxicities and by two levels (400 mg/m2) for the second episode. The induction cisplatin dose

was reduced by one level (15 mg/m2) after the first episode of grade 4 neutropenia and its

complications, grade 4 thrombocytopenia, creatinine clearance of 40–60 mL/min, or grade 2

neurotoxicity; and by two levels (30 mg/m2) for the second episode. Meanwhile, if the patient had

two episodes of grade 3 digestive reaction, the cisplatin dose was reduced by one level. The

concurrent cisplatin dose was reduced by one level (20 mg/m2) after the first episode of grade 3

neutropenia, grade 2 thrombocytopenia, grade 3 digestive reaction, creatinine clearance of 40–60

mL/min, or grade 2 neurotoxicity; and by two levels (40 mg/m2) for the second episode.

Chemotherapy was stopped completely after a grade 4 digestive reaction; grade 3 or higher elevated

alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase; creatinine clearance

of less than 40 mL/min; or grade 3 or higher pulmonary toxicity, ototoxicity, neurotoxicity, or

allergy.

In the induction or concurrent phase, a cycle could be delayed to allow the severity of the toxic

events to abate. Chemotherapy was withheld until the count of neutrophils was ≥ 1500 per μL,

platelets were ≥ 100000 per μL, and adequate liver and renal function were regained. Chemotherapy

was discontinued for delays greater than 2 weeks.

To prevent chemotherapy-induced nausea and vomiting, we recommended a triplet regimen

that consists 5-HT3-receptor antagonist (ondansetrone 8 mg or granisetron 3 mg, intravenously),

dexamethasone (10 mg intravenously) and NK-1-receptor antagonist (aprepitant 125 mg po on day

1 and 80 mg on days 2 and 3); metoclopramide (10 mg intramuscularly) could also be used if

symptoms persist despite the triplet combination. To prevent cisplatin-induced nephrotoxicity, we

administered a 3-day hydration protocol on days 0–2 and used diuretics (mannitol 50 g
3
intravenously and furosemide 20 mg intravenously) on the day of cisplatin administration. Severe

malnutrition or continuous weight loss during treatment was an indication for parenteral or

nasogastric nutritional supplementation. All of the supportive care could be delivered in both

inpatient and outpatient settings at the physician’s discretion. We allowed prophylactic granulocyte

colony-stimulating factor only in patients with a neutropenic infection or febrile neutropenia, grade

4 neutropenia lasting longer than 7 days during the preceding cycle, or no recovery of the absolute

neutrophil count at day 28. For grade 4 neutropenia, prophylactic antibiotics were administered.

4
Description of the guidelines for intensity-modulated radiation therapy (IMRT) in this trial

In general, all patients were immobilized in the supine position and using a thermoplastic mask that

covered the head, neck, and shoulder. Both non-enhanced CT (for dose calculation) and contrast-

enhanced CT (for target delineation) images were obtained from the vertex to 2 cm below the

sternoclavicular joint, with 3-mm slices.

Target volumes were defined in accordance with the International Commission on Radiation

Units and Measurements (ICRU) reports 50 and 62. Gross tumor volume (GTV) was defined as the

gross tumor determined by physical examination, imaging (including MRI and PET/CT, if available)

and endoscopic findings before induction chemotherapy or concurrent chemoradiotherapy,

including GTVnx and GTVnd. GTVnx included the sum of the primary tumor volume and the

enlarged retropharyngeal nodes, while GTVnd was the volume of involved gross cervical lymph

nodes. The high-risk clinical target volume (CTV1) was defined as the GTVnx plus a 5–10-mm

margin (2–3 mm posteriorly if adjacent to the brain stem or spinal cord) to encompass the high-risk

sites of microscopic extension and the whole nasopharynx. The low-risk clinical target volume

(CTV2) was defined as the CTV1 plus a 5–10-mm margin (2–3 mm posteriorly if adjacent to the

brain stem or spinal cord) to encompass the low-risk sites of microscopic extension, including the

clivus, sphenoid sinus, foramen lacerum, oval foramen, parapharyngeal space, pterygoid fossae,

posterior parts of the nasal cavity, pterygopalatine fossae, retropharyngeal nodal regions, the

cervical level where the involved lymph nodes were located, the elective neck area from level II to

Vb, and the supraclavicular fossae. Level Ib was electively irradiated if: (1) Level Ib lymph nodes

(LNs) were involved, (2) level IIa LNs had extracapsular extension or a diameter ≥ 3 cm, (3) there

was extensive nodal disease on the ipsilateral neck, and (4) the soft or hard palate, oral cavity, or

ipsilateral nasal cavity were grossly involved. A planning target volume (PTV) was created by

adding a three-dimensional margin of 3–5 mm to the delineated target volume to compensate for

the uncertainties in treatment set-up and internal organ motion. A 3-mm margin was added to the

critical organs (e.g., brainstem and spinal cord) to form the planning organ at risk volume (PRV).

The prescribed doses were 66–70 Gy, 64–70 Gy, 60–62 Gy, and 54–56 Gy, in 30–33 fractions,

for the PTVs derived from GTVnx, GTVnd, CTV1, and CTV2, respectively. The normal tissue dose
5
constraints are listed in Table SS1. All plans were generated by a team of dosimetrists using a whole-

field (including neck radiation) simultaneous integrated boost technique. In general, when critical

normal tissues (e.g., brain stem and spinal cord) were adjacent to the high-dose target volumes, the

target volume coverage could be compromised to keep these critical normal tissues within the dose

constraints. When other normal tissues of lower priority were adjacent to the high-dose target

volumes, the dose to these tissues was kept as low as possible without compromising the target

coverage. The trade-off between covering the target volume and protecting normal tissue in each

case was discussed and decided upon by the research team at each institution. Radiation was

delivered once daily at five fractions per week. It was recommended that patients in the induction

chemotherapy group commence chemoradiotherapy within 21-28 days from the first day of the last

cycle of induction chemotherapy.

Table SS1: Normal tissue dose constraints used for plan optimization
Structure Dose constraints
Spinal cord Dmax* ≤ 45 Gy
Spinal cord_PRV D1† ≤ 50 Gy
Brain stem Dmax ≤ 54 Gy
Brain stem_PRV D1 ≤ 60 Gy
Optic nerves Dmax ≤ 54 Gy
Optic nerves_PRV D1 ≤ 60 Gy
Optic chiasm Dmax ≤ 54 Gy
Optic chiasm_PRV D1 ≤ 60 Gy
Temporal lobe Dmax ≤ 60 Gy
Temporal lobe_PRV D1 ≤ 65 Gy
Lens Dmean‡ < 8 Gy
Pituitary Dmax < 60 Gy
Eyes Dmean < 35 Gy
Mandible Dmax < 70 Gy
Temporomandibular Joint Dmax < 70 Gy
Parotid Dmean < 26 Gy
V30§ < 50%
Cochlea Dmean < 50 Gy
Larynx Dmean < 45 Gy
PRV = planning organ at risk volume.
* Maximum point dose to the target volume.
† Dose received by 1% of the target volume.
‡ Mean dose to the target volume.
§ At least 50% of the gland will receive <30 Gy (should be achieved in at least one gland).

6
Definitions of the endpoints

Overall Survival was calculated from the date of randomization to death; distant recurrence-free

survival was calculated from the date of randomization to the date of documented distant metastasis

or death from any cause; locoregional recurrence-free survival was calculated from the date of

randomization to the date of documented locoregional recurrence or death from any cause. Patients

with a distant recurrence as a first event were censored for locoregional recurrence and vice versa.

If both distant and locoregional recurrences occurred at the same time, patients were considered as

having an event for both distant recurrence-free survival and locoregional recurrence-free survival.

Patients who were lost to follow-up, or are still alive without distant metastasis or locoregional

recurrence were censored at the date of last follow-up. Treatment responses were categorized as

complete response, partial response, stable disease and progressive disease based on the Response

Evaluation Criteria in Solid Tumors (version 1.1).1

References:

1. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours:
revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.

7
Per-protocol analysis

The per protocol population comprised of cases that received 3 cycles of induction gemcitabine

and cisplatin and 2-3 cycles of concurrent cisplatin plus radiotherapy in the induction

chemotherapy group and those received 3 cycles of concurrent cisplatin plus radiotherapy in

standard therapy group. The baseline characteristics of the patients were well balanced (table S2).

When analyzed by the per protocol population, 3-year recurrence-free (85.5% [80.8-89.7] vs.

77.8% [70.8-83.3]; figure S1A) and overall survival (95.5% [91.5-97.7] vs. 90.6% [85.0-94.1];

figure S1B) in favor of induction chemotherapy were observed.

8
Table S2: Patient baseline characteristics of per-protocol population *
Induction Chemotherapy Standard Therapy
Characteristic
(N = 218) (N = 177)
Sex
Male 164 (75.2%) 123 (69.5%)
Female 54 (24.8%) 54 (30.5%)
Age (years) 46 (18-64) 45 (20-64)
Karnofsky performance status score †
100 79 (4.1%) 10 (4.5%)
90 172 (78.9%) 198 (85.3%)
80 30 (13.8%) 21 (6.8%)
70 7 (3.2%) 9 (3.4%)
T category ‡
T1 2 (0.9%) 3 (1.7%)
T2 13 (6.0%) 10 (5.6%)
T3 104 (47.7%) 87 (49.2%)
T4 99 (45.4%) 77 (43.5%)
N category ‡
N1 104 (47.7%) 81 (45.8%)
N2 90 (41.3%) 79 (44.6%)
N3A 10 (4.6%) 5 (2.8%)
N3B 14 (6.4%) 12 (6.8%)
TNM stage ‡
III 100 (45.9%) 91 (51.4%)
IVA 94 (43.1%) 69 (39.0%)
IVB 24 (11.0%) 17 (9.6%)
Data are n (%) or median (range).
* Patients in the induction chemotherapy group received 3 cycles of gemcitabine plus cisplatin as
well as 2-3 cycles of concurrent cisplatin plus radiotherapy, and patients in the standard-therapy
group received 3 cycles of concurrent cisplatin plus radiotherapy. There were no significant
differences between the treatment groups in the characteristics at baseline.
† Karnofsky performance-status scores are assessed on a scale from 0 to 100, with lower scores
indicating greater disability.
‡ Tumor and node categories and disease stage were assessed according to the 7th edition of
American Joint Committee on Cancer–Union for International Cancer Control stage classification
system.

9
Figure S1: Kaplan-Meier Analysis of Recurrence-free Survival (A), Overall Survival (B),

Distant Recurrence-free Survival (C) and Locoregional Recurrence-free Survival (D) in the

two treatment groups (Per Protocol Population).

Per protocol population was defined as cases that received 3 cycles of induction gemcitabine and

cisplatin and 2-3 cycles of concurrent cisplatin with radiotherapy in the induction chemotherapy

group and those received 3 cycles of concurrent cisplatin with radiotherapy in the standard therapy

group. Hazard ratios and 95% confidence intervals were calculated by an unstratified Cox

proportional-hazards model. Tick marks indicate censored data.

10
Subgroup analysis

We performed an interaction analysis to explore if the effect of the experimental treatment varied

for the following subgroups (sex, age, performance status, T-category, N-category, and TNM-

stage). The subgroup analyses revealed a possible treatment interaction effect in the KPS

(unstratified HR 0.41 [95% CI 0.25-0.66], KPS 90-100 vs. HR 1.08 [95% CI 0.48-2.42], KPS 70-

80) and N-category (unstratified HR 1.22 [95% CI 0.63-2.36], N1 vs. HR 0.25 [95% CI 0.13-

0.49], N2 vs. HR 0.54 [95% CI 0.19-1.55], N3) subgroups (figure S2-5).

11
Figure S2: Forest plots of treatment effects on Recurrence-free Survival within subgroups.

Hazard ratios and 95% confidence intervals were calculated by an unstratified Cox proportional-
hazards model. HR = hazard ratio, CI = confidence interval.

Category No. of patients Hazard Ratio(95 %CI)

Overall 480 0.53(0.36-0.80)
Sex
Male 346 0.50(0.31-0.80)
Female 134 0.63(0.29-1.37)
Age
<45yrs 228 0.47(0.25-0.89)
>45yrs 252 0.58(0.35-0.99)
KPS score
90-100 407 0.41(0.25-0.66)
70-80 73 1.08(0.48-2.42)
T category
T1-2 37 0.16(0.02-1.40)
T3 231 0.74(0.38-1.41)
T4 212 0.47(0.27-0.81)
N category
N1 220 1.22(0.63-2.36)
N2 209 0.25(0.13-0.49)
N3 51 0.54(0.19-1.55)
Stage
III 231 0.56(0.28-1.13)
IVA 198 0.51(0.29-0.89)
IVB 51 0.46(0.15-1.40)
0.062 0.125 0.25 0.50 1.00 2.00

12
Figure S3: Kaplan-Meier Analysis of Recurrence-free Survival in the two treatment groups

stratified by different T classifications: (A) T1-2, (B) T3, (C) T4.

Hazard ratios and 95% confidence intervals were calculated by an unstratified Cox proportional-
hazards model. Tick marks indicate censored data.

13
Figure S4: Kaplan-Meier Analysis of Recurrence-free Survival in the two treatment groups

stratified by different N classifications: (A) N1, (B) N2, (C) N3.

Hazard ratios and 95% confidence intervals were calculated by an unstratified Cox proportional-
hazards model. Tick marks indicate censored data.

14
Figure S5: Kaplan-Meier Analysis of Recurrence-free Survival in the two treatment groups

stratified by KPS: (A) KPS = 90-100, (B) KPS = 70- 80.

Hazard ratios and 95% confidence intervals were calculated by an unstratified Cox proportional-
hazards model. Tick marks indicate censored data. KPS = Karnofsky performance status score.

15
Table S1: List of participating centers
Center Principal investigator
Sun Yat-sen University Cancer Center Jun Ma
Cancer Center, Tongji Hospital Affiliated to Tongji Medical College, Guo-Qing Hu
Huazhong University of Science and Technology
The First People’s Hospital of Foshan Ning Zhang
The Affiliated Cancer Hospital of Guangxi Medical University Xiao-Dong Zhu
Cancer Center, Union Hospital, Tongji Medical College, Huazhong Kun-Yu Yang
University of Science and Technology
Affiliated Hospital of Guizhou Medical University Feng Jin
XiJing Hospital of Forth Military Medical University Mei Shi
The Fifth Affiliated Hospital of Sun Yat-sen University Zhi-Bin Cheng
The Second Affiliated Hospital of Soochow University Ye Tian
The First Affiliated Hospital of Guangdong Pharmaceutical University Xi-Cheng Wang
Peking University Cancer Hospital Yan Sun
Jiangxi Cancer Hospital Jin-Gao Li

16
 Table S2: Compliance to gemcitabine and cisplatin induction chemotherapy
Induction Chemotherapy
Variable
Group
No. of patients randomized 242
Safety population (patients receiving IC) 239
Patients completing at least two cycles of IC, no. (%) 234 (97.9)
Patients completing three cycles of IC, no. (%) 231 (96.7)
Reason for discontinuation, no. (%)
Progressive disease 1 (0.4)
Adverse events 6 (2.5)
Related to treatment 6 (2.5)
Not related to treatment 0
Death 0
Consent withdrawn 1 (0.4)
Other 0 (0)
Patients with dose reductions, no. (%) 31 (13.0)
Reason for dose modification, no. (%)
Hematological 21 (8.8)
Non-hematological 9 (3.8)
Both hematological and non-hematological 1 (0.4)
Patients with at least one cycle delay > 3 days, no. (%) 71 (29.7)
Patients with at least one cycle delay > 7 days, no. (%) 21 (8.8)
Reason for delay, no. (%)
Adverse event 15 (6.3)
Other* 56 (23.4)
Median (interquartile) interval between first day of IC to first day of RT (days) 69 (67-75)
Median (interquartile) interval between day 1 of the last cycle of IC to first day of RT (days) 25 (22-28)
IC = induction chemotherapy; RT = chemoradiotherapy.
* Other reasons for treatment delays included logistics, personal reasons, and vacations.

17
 Table S3: Compliance to concurrent cisplatin chemotherapy and radiotherapy
Induction Standard
Variable
Chemotherapy Therapy
Safety population* 239 237
Patients receiving concurrent cisplatin, no. (%) 234 (97.9) 237 (100)
Patients completing at least two cycles CC, no. (%) 220 (92.1) 233 (98.3)
Patients completing three cycles CC, no. (%) 93 (38.9) 177 (74.7)
Patients receiving concurrent cisplatin ≥ 200 mg/m2, no. (%) 191 (79.9) 227 (95.8)
2
Patients receiving concurrent cisplatin 300 mg/m , no. (%) 63 (26.4) 140 (59.1)
Patients receiving RT, no. (%) 239 (100%) 237 (100%)
Patients completing RT, no. (%) 239 (100%) 235 (99.2%)
Median (IQR) dose of GTVp (Gy) 70 (70-70) 70 (70-70)
Median (IQR) dose per fraction (Gy) 2.12 (2.12-2.19) 2.12 (2.12-2.19)
Median (IQR) dose of CTV1 (Gy) 60 (60-62) 60 (60-62)
Median (IQR) dose of CTV2 (Gy) 54 (54-56) 54 (54-56)
Median (IQR) duration of RT (days) 45 (43-48) 45 (43-48)
CC = concurrent chemotherapy; RT = radiotherapy; IQR = interquartile range; GTVp= gross tumor
volume of the primary tumor; CTV1= high-risk clinical target volume; CTV2= low-risk clinical
target volume.
* The safety population comprised of cases that started induction chemotherapy in the induction
chemotherapy arm and concurrent chemotherapy in the standard-therapy arm.

18
Table S4: Adverse events, according to trial group and grade. *
Induction Standard
Variable Chemotherapy Therapy
(N = 239) (N = 237)
Adverse events during induction chemotherapy
Total Grade 3-4 adverse events† 93 (38.9%)
Neutropenia 49 (20.5%)
Leukopenia 26 (10.9%)
Anemia 4 (1.7%)
Thrombocytopenia 13 (5.4%)
Nausea 22 (9.2%)
Vomiting 26 (10.9%)
Mucosits 2 (0.8%)
Diarrhea 1 (0.4%)
Hepatoxicity 5 (2.1%)
Nephrotoxicity 3 (1.3%)
Allergic reaction 1 (0.4%)
Adverse events during concurrent chemoradiotherapy
Total Grade 3-4 adverse events 156 (65.3%) 131 (55.3%)
Leukopenia 47 (19.7%) 48 (20.3%)
Neutropenia 28 (11.7%) 25 (10.5%)
Febrile neutropenia 1 (0.4%) 0
Anemia 19 (7.9%) 2 (0.8%)
Thrombocytopenia 17 (7.1%) 3 (1.3%)
Stomatitis (mucositis) 67 (28.0%) 76 (32.1%)
Vomiting 42 (17.6%) 33 (13.9%)
Nausea 43 (18.0%) 33 (13.9%)
Dry mouth 12 (5.0%) 6 (2.5%)
Diarrhea 5 (2.1%) 4 (1.7%)
Dermatitis 5 (2.1%) 9 (3.8%)
Weight loss 5 (2.1%) 4 (1.7%)
Nephrotoxicity 3 (1.3%) 1 (0.4%)
Hepatoxicity 1 (0·4%) 0
* This analysis was conducted in the safety population, which included only patients who started
the trial treatment.

19
Table S5: Disease recurrence distribution in the two treatment groups.
Induction Standard
Chemotherapy Therapy
(N = 242) (N = 238)
Disease recurrence 37 (15.3) 63 (26.5)
Distant 23 (9.5) 40 (16.8)
Bone 9 (3.7) 8 (3.4)
Lung 8 (3.3) 10 (4.2)
Liver 4 (1.7) 8 (3.4)
Other 0 2 (0.8)
Multiple 2 (0.8) 12 (5.0)
Locoregional 17 (7.0) 22 (9.2)
Local alone 6 (2.5) 11 (4.6)
Regional alone 5 (2.1) 6 (2.5)
Local + regional 6 (2.5) 5 (2.1)
Distant + Locoregional 6 (2.5) 4 (1.7)
Distant + local 2 (0.8) 0
Distant + regional 1 (0.4) 1 (0.4)
Distant + local + regional 3 (1.3) 3 (1.3)
Death 18 (7.4) 35 (14.7)
Cancer-specific 16 (6.6) 32 (13.4)
Non-cancer-specific 2 (0.8) 3 (1.3)
Nasopharyngeal necrosis 1 (0.4) --
Osteomyelitis of skull base -- 1 (0.4)
Cardiovascular and cerebrovascular diseases -- 1 (0.4)
Car accident 1 (0.4)
Unknown 1 (0.4) --
Data are n (%).

20
Table S6: Salvage treatments after disease recurrence
Induction Standard
Treatment type
Chemotherapy Therapy
Treatment after locoregional recurrence N = 17 N = 22
Surgery 4 4
Radiotherapy 2 2
Chemotherapy 2 4
Multiple 4 6
Supportive care 4 5
Unknown 1 1
Treatment after distant recurrence N = 23 N = 40
Surgery 1 2
Radiotherapy 1 2
Chemotherapy 12 22
Multiple 5 6
Supportive care 4 6
Unknown 0 2
Data are numbers.

21
 Table S7: Comparison of acute adverse events of concurrent chemoradiotherapy with
induction GP versus induction TPF
Maximum grade per GP TPF *
patient during treatment Grade 3 Grade 4 Grade 5 Grade 3 Grade 4 Grade 5
Induction phase
Any 33.5% 5.4% 0 27.6% 15.1% 0.4%
Hematologic
Neutropenia 17.2% 3.3% 0 20.5% 14.6% 0.4%
Febrile neutropenia 0 0 0 1.3% 0.4% 0
Neutropenic infection 0 0 0 0.4% 0 0.4%
Leukopenia 10.0% 0.8% 0 23.0% 4.2% 0
Anemia 1.2% 0.4% 0 0.4% 0 0
Thrombocytopenia 4.6% 0.8% 0 0 0 0
Non-hematologic
Nausea 7.9% 1.3% 0 4.2% 0 0
Vomiting 10.0% 0.8% 0 3.4% 0 0
Diarrhea 0.4 0 0 8.0% 0 0
Stomatitis (mucositis) 0.8 0 0 5.4% 0.8% 0
Hepatoxicity 2.1% 0 0 2.5% 0
Renal toxicity 1.3% 0 0 0 0 0
Allergic reaction 0.4% 0 0 0.8% 0 0
Concurrent Phase
Any 62.3% 2.9% 0 56.5% 2.9% 0
Hematologic
Leukopenia 19.7% 0 0 18.4% 1.3% 0
Neutropenia 11.7% 0 0 11.3% 1.3% 0
Febrile neutropenia 0 0 0 0.8% 0.4% 0
Anemia 7.5% 0.4% 0 1.7% 0 0
Thrombocytopenia 5.9% 1.3% 0 2.1% 0.4% 0
Non-hematological
Mucositis 27.6% 0.4% 0 38.5% 0 0
Vomiting 16.7% 0.8% 0 20.5% 1.7% 0
Nausea 17.2% 0.8% 0 18.8% 1.7% 0
Dry mouth 5.0% 0 0 5.4% 0 0
Diarrhea 2.1% 0 0 0 0 0
Dermatitis 2.1% 0 0 3.3% 0.4% 0
Weight loss 2.1% 0 0 1.3% 0 0
Renal toxicity 1.3% 0 0 0 0 0
Hepatoxicity 0.4% 0 0 0.4% 0 0
GP = gemcitabine + cisplatin; TPF = docetaxel+cisplatin+5-fluorouracil.
*
Sun Y, Li WF, Chen NY, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus
concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a
phase 3, multicentre, randomised controlled trial. Lancet Oncol 2016;17:1509-20.
22