翻譯公司資訊

世聯(lián)翻譯公司完成醫(yī)學(xué)英文翻譯

發(fā)布時(shí)間：2018-04-23 12:56　　點(diǎn)擊：

Phase III, Multicenter, Randomized Trial of Maintenance

Chemotherapy Versus Observation in Patients With

Metastatic Breast Cancer After Achieving Disease Control

With Six Cycles of Gemcitabine Plus Paclitaxel

As First-Line Chemotherapy: KCSG-BR07-02

Yeon Hee Park, Kyung Hae Jung, Seock-Ah Im, Joo Hyuk Sohn, Jungsil Ro, Jin-Hee Ahn, Sung-Bae Kim,

Byung-Ho Nam, Do Youn Oh, Sae-Won Han, Soohyeon Lee, In Hae Park, Keun Seok Lee, Jee Hyun Kim,

Seok Yun Kang, Moon Hee Lee, Hee Sook Park, Jin Seok Ahn, and Young-Hyuck Im

See accompanying editorial doi: 10.1200/JCO.2013.48.6894 Yeon Hee Park, Jin Seok Ahn, and Young-

Hyuck Im, Samsung Medical Center, Sungkyunkwan

University School of Medicine;

Kyung Hae Jung, Jin-Hee Ahn, and Sung-

Bae Kim, Asan Medical Center, University

of Ulsan College of Medicine; Seock-Ah

Im, Do Youn Oh, and Sae-Won Han, Seoul

National University Hospital, Cancer

Research Institute, Seoul National University,

College of Medicine; Joo Hyuk Sohn

and Soohyeon Lee, Yonsei University

College of Medicine; Hee Sook Park, Soonchunhyang

University Hospital, Seoul;

Jungsil Ro, Byung-Ho Nam, In Hae Park,

and Keun Seok Lee, National Cancer

Center, Goyang; Jee Hyun Kim, Seoul

National University Bundang Hospital,

Cancer Research Institute, Seoul National

University College of Medicine, Seongnam;

Seok Yun Kang, Ajou University School of

Medicine, Suwon; Moon Hee Lee, Inha

University School of Medicine, Incheon,

Korea.

Published online ahead of print at

www.jco.org on April 8, 2013.

Written on behalf of the Korean Cancer

Study Group.

Support information appears at the end

of this article.

Both Y.H.P. and K.H.J. contributed equally

to this work.

Authors’ disclosures of potential conflicts

of interest and author contributions are

found at the end of this article.

Clinical trial information: NCT00561119.

Corresponding author: Young-Hyuck Im,

MD, PhD, Division of Hematology/Oncology,

Department of Medicine, Samsung

Medical Center, Sungkyunkwan University

School of Medicine, 50 Irwon-dong

Gangnam-gu, Seoul 135-710, Korea; e-mail:

imyh00@skku.edu.

Oncology

0732-183X/13/3199-1/$20.00

DOI: 10.1200/JCO.2012.45.2490

A B S T R A C T

Purpose

The primary purpose of our study was to evaluate whether maintenance chemotherapy with

paclitaxel/gemcitabine (PG) was superior to observation in improving progression-free survival

(PFS) in patients with metastatic breast cancer (MBC) who achieved disease control with an initial

six cycles of PG as their first-line treatment.

Patients and Methods

The study was a prospective, randomized, multicenter, phase III trial. Patients MBC with who

achieved disease control after six cycles of PG chemotherapy were randomly assigned to

maintenance chemotherapy or observation until progression.

Results

Of 324 patients from 10 centers enrolled, 231 patients with MBC exhibited disease control

(complete response partial response stable disease) with first-line PG and were randomly

assigned to maintenance chemotherapy (n 116) or observation (n 115). The median age

was 48 years (range, 28 to 76 years), median follow-up was 33 months, and median number

of chemotherapy cycles in the maintenance group after random assignment was six. The

median PFS time after random assignment was longer in the maintenance group than in the

observation group (7.5 v 3.8 months, respectively; P .026). The median overall survival (OS)

time was longer in the maintenance group than in the observation group (32.3 v 23.5 months,

respectively; P .047). The rate of grade 3 or higher neutropenia after random assignment

was higher in the maintenance group than in the observation group (61% v 0.9%, respectively;

P .001).

Conclusion

In patients with MBC who achieved disease control with an initial six cycles of PG chemotherapy,

maintenance PG chemotherapy resulted in better PFS and OS compared with observation.

INTRODUCTION

Metastatic breast cancer (MBC) is an incurable disease

with a 2- to 3-year median overall survival (OS)

time.1,2 The therapeutic goals are palliative and include

prolongation of survival with good quality of

life (QoL) and symptom control. Therefore, the

management ofMBCis a clinical challenge for medical

oncologists.

Chemotherapy is generally recommended in

patients with hormone receptor (HR) –negative tumors,

endocrine-resistant disease of the luminal

subtype, and rapidly proliferative and/or symptomatic

disease. However, the optimal duration of firstline

chemotherapy in the treatment ofMBCremains

controversial. Several trials have reported that continuous

chemotherapy prolongs the duration of remission,

but its effect on survival and QoL are less

consistent.3-11Arecent meta-analysis of 11 randomized

trials reported that a longer treatment duration

of first-line chemotherapy was associated with a

substantially longer progression-free survival (PFS)

JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T

The latest version is at http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2012.45.2490

Published Ahead of Print on April 8, 2013 as 10.1200/JCO.2012.45.2490

202.195.183.214

Information downloaded from jco.ascopubs.org and provided by at Nanjing Medical University on April 10, 2013 from

and marginally longer OS in patients with MBC.12 However, this

meta-analysis included only three recent studies incorporating

taxane-based chemotherapeutic regimens, which are the current standard

of care. In addition, most of the studies in the meta-analysis did

not address QoL issues. The relative benefits of tumor regression and

improvement in disease-related symptoms provided by chemotherapy

must be balanced with treatment-induced toxicity and its impact

on QoL, even if prolonged chemotherapy has a survival benefit.

Therefore, it is crucial to choose proper first-line chemotherapeutic

agents for maintenance treatment. Recently, two taxanecontaining

chemotherapy regimens have shown significantly

improved responses and PFS and modestly improved OS compared

with single-agent chemotherapy as the first-line treatment.

Capecitabine and docetaxel (CD) were shown to be superior to

docetaxel alone, and paclitaxel and gemcitabine (PG) were found

to have better efficacy than paclitaxel alone without a clinically

meaningful increase in toxicity.13,14

No differences in response rate, PFS, and OS were observed in a

comparison of gemcitabine and docetaxel with CD.15 However, the

nonhematologic toxicity profile favored gemcitabine and docetaxel

over CD, suggesting that gemcitabine may be a better therapeutic

option than capecitabine when combined with a taxane for the treatment

of MBC. This is notable because combination chemotherapy

with PG is the preferred first-line treatment in patients with MBC.

The question remains whether continuation with PG in the

maintenance period after achieving an initial response is feasible when

toxicity and QoL are taken into account. Although single-agent treatment

with gemcitabine or paclitaxel may be superior in terms of

toxicity, the efficacy of single-agent treatment in patients who responded

to initial PG chemotherapy remains unproven. Furthermore,

PG chemotherapy was well tolerated in a previous study and

showed survival benefits in the treatment of MBC.

On the basis of this rationale, we hypothesized that patients with

MBC who achieve disease control with an initial six cycles of PG

chemotherapy would have a longer PFS with maintenance PG chemotherapy

compared with observation. The primary purpose of the

study was to determine whether maintenance PG chemotherapy is

superior to observation in prolonging PFS in patients withMBCwith

disease control after six cycles of PG chemotherapy.

PATIENTS AND METHODS

Eligibility Criteria

Womenwith histologically confirmed metastatic or recurrent breast cancer

wereeligible for the study.Bothpremenopausalandpostmenopausalwomenwith

measurable and/or nonmeasurable lesion(s)whowere candidates for chemotherapy

and who had no prior history of chemotherapy in the metastatic setting were

eligible. Patients were eligible for the study if it had been at least 12 months since

completion of the prior chemotherapy, even if theyhadreceived an anthracyclineor

taxane-containing regimen as neoadjuvant or adjuvant therapy. Patients who

had received hormonal therapy in the adjuvant and/or metastatic setting were

eligible, but hormonal therapy was terminated before random assignment. Patients

who had received radiation to less than 25% of their bone marrow and had

recovered from the acute toxic effects of the treatment were eligible. Additional

requirements included age 18 years or older with an Eastern Cooperative Oncology

Group performance status of 0 to 2; adequate bone marrow, renal, and liver

function; and absence of other concurrent or previous malignant neoplasms, with

the exception of adequately controlled in situ uterine carcinoma and/or cutaneous

basal cell carcinoma.

The exclusion criteria were prior chemotherapy for MBC, clinically detectable

brain parenchymal and/or leptomeningeal metastases, prior treatment with

gemcitabine, other severe medical conditions, and human epidermal growth factor

receptor 2–positive breast cancer treated with trastuzumab.

Study Design

This study is a multicenter, phase III study of the Korean Cancer Study

Group (KCSG; KCSG-BR07-02) with a randomized discontinuation design. Patients

who achieved disease control (complete response [CR], partial response

[PR], or stable disease) after the initial six cycles of PG chemotherapy were randomly

assigned, in a 1:1 ratio, to either the maintenancePGchemotherapyarmor

the observation arm. Patients were accrued from 10 institutes in Korea. Registration

and random assignment were coordinated centrally at theKCSGdata center.

The random permutation method was used for random assignment. The stratification

factors for random assignment were the presence or absence of visceral

disease, prior adjuvant taxane therapy, response (CR/PR v stable disease) to the

initial six cycles of PG chemotherapy, andHRstatus (positive v negative; Fig 1A).

Chemotherapy was started within 14 days after random assignment. Treatment

comprised paclitaxel175mg/m2 intravenousonday1andevery21days thereafter

and gemcitabine 1,250 mg/m2 administered as a 30-minute intravenous infusion

on days 1 and 8 and every 21 days thereafter.

The patients randomly assigned to the maintenance arm continued with

PG chemotherapy until disease progression, development of unacceptable

toxicity, or withdrawal of consent. The patients randomly assigned to observation

were observed without any treatment until disease progression or

withdrawal of consent. Hormonal therapy was not allowed in either group of

patients after random assignment before disease progression.

The study was conducted in full accordance with the guidelines for Good

Clinical Practice and the Declaration of Helsinki and was approved by the

institutional ethics committees of each hospital and the KCSG Institutional

Review Board (ClinicalTrials.gov identifier: NCT00532857). Written informed

consent was obtained from each participant.

Study Evaluation

The prestudy clinical evaluation included a physical examination; vital

signs with performance status; chest x-ray; computed tomography scans of the

chest, abdomen, and pelvis; and a bone scan. Blood chemistry results and

CBCs were obtained for every treatment cycle. Radiographic studies were

performed every 6 weeks. Toxicity was assessed on the first day of each cycle.

OS was measured from the date of random assignment to the date of

death from any cause, with censoring of the last visit date. PFS was calculated

from the date of random assignment to the documented date of disease

progression or the last visit date. Disease response was assessed according to

RECIST (version 1.0).16,17 The duration of the response was measured from

the time of chemotherapy to the date of disease progression. PFS and the

duration of response were assessed by investigators. Toxicity was assessed at

the end of each cycle using National Cancer Institute Common Terminology

Criteria for Adverse Events (version 3.0).

Dose Modifications

On the planned day of therapy, if the absolute neutrophil count (ANC)

was less than 1.5109/L and/or the platelet count was less than 100109/L,

chemotherapy was delayed 1 week. If the ANC and platelet counts were

satisfactory after 1 week, the full intended dose of chemotherapy was given.

However, if after 1 week, the ANC was still less than 1.5 109/L and/or the

platelet count was less than 100 109/L, chemotherapy was given at 75% of

the original intended dose. Treatment was delayed and the dose was reduced in

patients who experienced a second occurrence of a grade 2 nonhematologic

toxicity (except alopecia or nausea/vomiting) or any grade 3 toxicity. In patients

with grade 2 peripheral neuropathy, the dose of paclitaxel was reduced.

In patients with grade 3 neuropathy, paclitaxel was discontinued. Both drugs

were discontinued if one of the drugs was discontinued.

Statistical Methods

Theprimaryendpoint wasPFSafterrandomassignment. Secondaryend

points included OS, QoL, toxicity, and response duration. We hypothesized

that PFS would be longer in the maintenance chemotherapy group compared

with the observation group. A 20% longer 6-month PFS rate was expected in

Park et al

202.195.183.214

Information downloaded from jco.ascopubs.org and provided by at Nanjing Medical University on April 10, 2013 from

the maintenance group compared with the observation group. With 90%

power and 5% one-sided type I error, and considering a 10% follow-up loss,

we calculated that 244 patients were needed at the time of random assignment

and a total of 326 patients were needed at the time of enrollment.

All randomly assigned patients were included in the efficacy analysis according

to the intent-to-treat principle, and patients who received at least one dose of

study medication were evaluated for safety. Observations were censored at the last

clinical contact if patientswerelost to follow-up or at the cutoff date for the analysis

(October 31, 2011). PFS and OS were estimated using the Kaplan-Meier method

and were compared using the log-rank test. Analyses of treatment effects were

adjusted for covariates selected before the analysis using a multivariate Cox proportional

hazards model with stratification according to the visceral disease, age,

menopausal status, performance status,numberof metastatic sites, prior adjuvant

taxane therapy, disease response, and HR status. Differences were considered

statistically significant at P.05 with a two-tailed test.

RESULTS

Patient Characteristics

A total of 324 patients were enrolled from 10 centers in Korea

from August 2007 to September 2010. Of these, 231 patients who

achieved disease control with an initial six cycles of PG chemotherapy

were randomly assigned to either maintenance PG chemotherapy

(n116) or observation (n115; Fig 1B). The baseline characteristics

of the patients were similar between the two groups (Table 1). The

median ages of patients were 48 and 47 years in the maintenance and

observation groups, respectively, and about half of the patients were

premenopausal women. The number of HR-positive patients was 85

(73.3%) in the maintenance group and 87 (75.7%) in the observation

group. Forty-two patients (36.2%) in the maintenance group and 38

patients (33.0%) in the observation group had received adjuvant taxane

(P.613). Palliative hormonal therapy because of metastasis had

been administered before enrollment in 20 patients (17.2%) in the

maintenance group and 26 patients (22.4%) in the observation group.

Dose Administration

Atotal of 768 cycles ofPGchemotherapy (median, six additional

cycles) were received in the maintenance group after randomization.

Including the six cycles of chemotherapy administered before random

assignment, the median dose-intensity of gemcitabine was 721.9

mg/m2 per week (86.6% of the expected dose; interquartile range

[IQR], 645.3 to 721.9mg/m2 per week) in the maintenance group and

763.9 mg/m2 per week (91.7% of the expected dose; IQR, 694.5 to

763.9 mg/m2 per week) in the observation group. The median doseintensity

of paclitaxel was 55.2mg/m2 per week (94.7% of the expected

dose; IQR, 49.7 to 55.2 mg/m2 per week) in the maintenance group

and 55.9 mg/m2 per week (95.9% of the expected dose; IQR, 53.5 to

55.9 mg/m2 per week) in the observation group.

Patients with MBC

and no previous

chemotherapy

(N = 324)

PD Withdrawn from study

Observation until PD

••••••• Until PD

6 cycles of PG

Stratification

1. Visceral v nonvisceral

2. Previous adjuvant taxane

3. Response (CR/PR v SD)

4. HR positive v HR negative

CR/PR/SD R

Enrollment

(n = 324)

Randomly assigned

(n = 231)

Reason for discontinuation

Progression (n = 50)

Adverse event (n = 12)

Withdrawal (n = 17)

Death as result of disease (n = 2)

Physician/patient discretion (n = 12)

Reasons for stopping the study drugs

Progression (n = 40)

Adverse event (n = 13)

Withdrawal (n = 14)

Death as result of disease (n = 0)

Physician/patient discretion (n = 33)

Other (n = 9)

Reasons for stopping the study drugs

Progression (n = 80)

Adverse event (n = 0)

Withdrawal (n = 13)

Death as result of disease (n = 0)

Physician/patient discretion (n = 6)

Other (n = 6)

Maintenance*

(n = 116)

Observation*

(n = 115)

Fig 1. (A) Treatment scheme. (B) CONSORT

flow diagram. (*) Patients included

in the final analyses of survival and secondary

efficacy variables with intent-totreat

principle. CR, complete response;

HR, hormone receptor; MBC, metastatic

breast cancer; PD, progressive disease;

PG, paclitaxel and gemcitabine; PR, partial

response; R, random assignment; SD, stable

disease.

Maintenance Paclitaxel/Gemcitabine for Metastatic Breast Cancer

202.195.183.214

Information downloaded from jco.ascopubs.org and provided by at Nanjing Medical University on April 10, 2013 from

Efficacy Analysis

The overall response rate and disease control rate of the initial six

cycles of PG chemotherapy in 324 patients were 50.0% and 78.6%,

respectively. The median PFS time from random assignment was

prolonged by 3.7 months in the maintenance group, from 3.8 months

in the observation group to 7.5 months in the maintenance group

(hazard ratio, 0.73; 95% CI, 0.55 to 0.97; P .026; Fig 2A). The

6-month PFS rate after random assignment, which was the primary

end point of this study, was 59.7% in the maintenance arm and 36.0%

in the observation arm—a 66% difference (P .001; Fig 2A). In all

patients, the median OS time from random assignment was 26.3

months (95% CI, 19.6 to 32.9 months). The median OS time from

random assignment was longer in the maintenance group than in the

observation group (32.3 v 23.5 months, respectively; hazard ratio,

0.65; 95% CI, 0.42 to 0.99; P.047; Fig 2B).

The PFS benefits of maintenance chemotherapy were observed

in patients younger than 50 years of age (95% CI, 0.33 to 0.74;

P .001), premenopausal women (95% CI, 0.34 to 0.79; P .002),

patients with a response (CR or PR; 95% CI, 0.46 to 0.95; P .024),

patients with visceral disease (95% CI, 0.49 to 0.98; P.041), patients

with HR-negative disease (95% CI, 0.30 to 0.90; P .019), and

patients with two or more metastases (95% CI, 0.47 to 0.93; P.029;

Fig 2C). The response durations were 9.6 and 7.8 months in the

maintenance and observation groups, respectively.

The reasons for nonadherence to randomly assigned treatment

in the absence of progression differed between the two

groups (Table 2). Eighty (69.6%) of 115 patients in the observation

arm and 40 (34.5%) of 116 patients in the maintenance arm

experienced disease progression. In the maintenance group, 33

patients whose disease had not progressed stopped further chemotherapy

at the physician’s discretion. The median number of

chemotherapy cycles for these patients after random assignment

was 12 (range, nine to 26 cycles). Patients who stopped the study

drugs at the physician’s discretion did not receive further anticancer

treatment, including endocrine therapy, until disease progression

was documented.

Table 1. Patient Characteristics in Maintenance Arm and Observation Arm

Characteristic

Maintenance (n 116) Observation (n 115)

No. of Patients % No. of Patients % P

Age, years .768 (t test)

Median 48 47

Range 30-70 29-76

ECOG PS .980

0 58 50.4 57 49.1

1 55 47.8 57 49.1

2 2 1.7 2 1.7

Menopausal status .643

Premenopausal 56 48.3 53 46.1

Postmenopausal 56 48.3 60 52.2

Unknown 4 3.4 2 1.7

IDC v others 107 92.2 112 97.4 .135

HR status

Positive 85 73.3 87 75.7 .679

Negative 31 26.7 28 24.3

HER2 positive 2 1.7 2 1.7 .950

No. of metastatic sites .342

1 32 27.6 38 33.0

2 37 31.9 44 38.3

3 47 40.5 33 28.7

Metastatic sites

Distant lymph nodes 78 67.2 62 53.9 .320

Lung, hematogenous 37 31.9 19 16.5 .029

Lung, lymphangitic 26 22.4 31 27.0 .218

Liver 41 35.3 34 29.6 .776

Bone 53 45.7 50 43.5 .685

Pleura 21 18.1 12 10.4 .192

Others 2 1.7 1 0.9 .503

Visceral metastases 81 69.8 74 64.3 .375

Prior adjuvant chemotherapy

Anthracycline 67 57.8 57 49.6 .212

Taxane 42 36.2 38 33.0 .613

Prior adjuvant endocrine therapy 53 45.7 42 36.5 .182

Palliative endocrine therapy before PG chemotherapy 26 22.4 20 17.4 .339

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group performance status; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; IDC,

invasive ductal carcinoma; PG, paclitaxel and gemcitabine.

HR positive status indicates estrogen receptor positive and/or progesterone receptor positive; HR negative status indicates estrogen receptor negative and

progesterone receptor negative.

Park et al

202.195.183.214

Information downloaded from jco.ascopubs.org and provided by at Nanjing Medical University on April 10, 2013 from

Systemic Treatments After Progression

The details of the systemic treatment after progression are listed

in Table 3. A total of 165 patients (71.4%) received additional chemotherapy.

Seven hundred seventy-nine cycles of chemotherapy were

given in the maintenance group, and 708 cycles of chemotherapy were

given in the observation group. PG combination chemotherapy was

not given to any patient in the observation group after progression,

whichmeansthat there wasnocross over.Hormonaltherapy was used

in patients with HR-positive disease. A total of 41% of patients received

hormonal therapy. The types of additional hormonal therapy

were similar in the two groups.

Toxicity Analysis

Table4liststhedrug-relatedtoxicities(accordingtoNationalCancer

InstituteCommonTerminology Criteria for Adverse Events) per patient

observed. Hematologic toxicity of all grades was observed more frequently

in the maintenancegroupthan the observationgroup(neutropenia,

87.1% v 30.4%, respectively; P.001; thrombocytopenia, 25.9% v

Hazard ratio, 0.73 (95% CI, 0.55 to 0.97)

P = .026

6-month PFS rate after random assignment

59.7% v 36.0% (P < .001)

PFS

(probability)

Time (months)

1.0

0.8

0.6

0.4

0.2

No. at risk

Maintenance 116 68 25 11 5 2 0 0 0

Observation 115 41 19 11 6 4 1 0 0

Trial Arm Events Median 95% CI

Maintenance 97 7.5 6.2 to 8.9

Observation 96 3.8 2.4 to 5.3

0 6 12 18 24 30 36 42 48

Hazard ratio, 0.65 (95% CI, 0.42 to 0.99)

P = .047

Overall Survival

(probability)

Time (months)

1.0

0.8

0.6

0.4

0.2

No. at risk

Maintenance 116 112 88 57 26 17 5 0 0

Observation 115 110 71 50 26 13 7 1 0

Trial Arm Events Median 95% CI

Maintenance 37 32.3

Observation 49 23.5 18.9 to 28.1

0 24 30 36 42 48

Favors maintenance Favors observation

6 12 18

n Hazard Ratio 95% Cl

Menopausal status

Premenopausal 109 0.52 0.34 to 0.79

Postmenopausal 116 0.98 0.68 to 1.49

Performance status

0 115 0.69 0.46 to 1.03

1-2 116 0.77 0.52 to 1.15

Age group, years

≤ 50 139 0.50 0.33 to 0.74

> 50 92 1.03 0.69 to 1.56

Response to PG #6

CR+ PR 143 0.66 0.46 to 0.95

SD 88 0.82 0.50 to 1.35

Disease type

Visceral 155 0.70 0.49 to 0.98

Nonvisceral 76 0.82 0.50 to 1.35

Tumor subtype

HR positive 172 0.79 0.56 to 1.10

HR negative 59 0.52 0.30 to 0.90

No. of metastases

1 70 0.86 0.50 to 1.47

≥ 2 161 0.66 0.47 to 0.93

Overall 231 0.73 0.55 to 0.97

0.0 0.5 1.0 1.5 2.0

Fig 2. (A) Progression-free survival (PFS) after random assignment in the maintenance and observation groups. (B) Overall survival after random assignment in the maintenance and

observation groups. (C) Forest plots (PFS analysis). CR, complete response; HR, hormone receptor; PG, paclitaxel and gemcitabine; PR, partial response; SD, stable disease.

Maintenance Paclitaxel/Gemcitabine for Metastatic Breast Cancer

202.195.183.214

Information downloaded from jco.ascopubs.org and provided by at Nanjing Medical University on April 10, 2013 from

12.2%, respectively; P.008; and anemia, 87.9% v 64.3%, respectively;

P.001). The rate of grade 3 or higher neutropenia was much higher in

the maintenance group than in the observation group (61% v 0.9%,

respectively; P.001). QoL did not differ between the two groups (data

not shown). Additional data will be reported in a separate article.

DISCUSSION

It is important to realize that patients with MBC are a heterogeneous

group, and thus the strategies for treatment differ depending on the

circumstances of the individual patient.18 For patients with human

epidermal growth factor receptor 2–positive MBC, trastuzumab in

combination with cytotoxic chemotherapy has transformed the prognosis,

and this combination therapy is recommended as the first-line

treatment.19 For patients with HR-positive disease, hormonal therapy

is considered initially. It can be assumed that nearly all patients with

MBCwill eventually require chemotherapy, particularly patients with

HR-negative or hormone-resistant disease.

Several clinical trials have attempted to identify the optimal duration

of first-line chemotherapy in the treatment of MBC.3-7,10-12,20

However, one limitation of these results is that in some of the early

studies, the chemotherapeutic regimens were suboptimal compared

with most recent regimens involving modern drugs. In addition, the

extension of full-dose chemotherapy after disease control may be

considered an outdated concept and may not be feasible because of

excessive toxicity and a negative impact on QoL.

Our study has several major strengths. First,PGchemotherapy is

one of two chemotherapeutic regimens that have shown a definite

survival advantage as a first-line treatment of MBC without clinically

relevant toxicity in randomized trials.14 We selected patients who had

already demonstrated at least disease stabilization to this regimen,

thereby enriching for thosewhomight benefit from maintenance. The

improved PFS in the maintenance group translated to a prolongation

of OS irrespective of HR status.

Second, in the Maintenance Paclitaxel 1 (MANTA1) trial, in

which the concurrent use of endocrine therapy with chemotherapy

was allowed, the concurrent use of antiestrogen with chemotherapy

might be regarded as a confounding factor in the interpretation of the

results. Because hormonal therapy would affect PFS, in our study,

patients with HR-positive disease were not allowed to receive hormonal

therapy until disease progression, which is unique compared

with previous studies.11 Third, our trial highlighted subgroups of

patientswhowould have benefited from maintenancePGchemotherapy,

although this was the result of the subset analyses. These subgroups

are patients with MBC who are younger and premenopausal,

who have HR-negative tumors, who demonstrated a response to PG

chemotherapy, and who had rapidly progressive visceral disease and a

high tumor burden. Although a survival benefit was shown in all

patients, including HR-positive patients, the main role of maintenancePGchemotherapymaybe

in patients with HR-negative tumors.

Interestingly, approximately half of the patients were premenopausal

and young. These findings imply an aggressive tumor behavior,

which necessitates cytotoxic chemotherapy. The treatment regimen,

duration, sequence, and order of palliative chemotherapy are major

challenges yet to be defined for patients withMBCwith triple-negative

disease and HR-positive tumors with visceral metastases after failure

of hormonal treatment. In this regard, our study showed promising

results that can be adapted to current practice. Given the observed OS

Table 2. Reasons for Study Discontinuation

Reason

No. of Patients

Maintenance Arm

(n 116)

Observation Arm

(n 115)

Disease progression 40 80

Patient withdrawal 14 13

Adverse events 13 0

Grade 4 neutropenia 2

Grade 2-3 neuropathy 10

Grade 3 hepatotoxicity 1

Physician’s discretion 33 6

Physician/patient’s shared decision 33

Palliative local treatment 4

Switch to other chemotherapy 2

Other 9 6

Endocrine therapy 2 4

Comorbidity 5 2

Second primary malignancy 2

Median, 12 cycles; range, nine to 26 cycles.

Table 3. Systemic Treatment After Progression

Variable

Maintenance

Arm

(n 116)

Observation

Arm

(n 115)

No. % No. % P

No. of subsequent

chemotherapy regimens .933

Total 82 70.6 83 72.1

1 33 28.4 28 24.3

2 23 19.9 27 23.5

3 26 22.6 28 24.3

Median 2.7 2.6 .588 (t test)

No. of total cycles 779 708

Type of chemotherapy

Fluorouracil 16 13.8 18 15.7

Capecitabine 52 44.8 65 56.5

Cisplatin 14 12.1 18 15.7

Cyclophosphamide 40 34.5 32 27.8

Anthracycline 37 31.9 30 26.1

Docetaxel 19 16.4 22 19.1

Vinorelbine 29 25 29 25.2

Methotrexate 5 4.3 11 9.6

Gemcitabine 11 9.5 16 13.9

Trastuzumab 1 0.8 2 1.7

Other 29 25 20 17.4

No. of subsequent endocrine

therapies .268

Total 49 42.2 45 39.1

1 43 37.0 35 30.4

2 6 5.2 8 7.0

3 0 0 2 1.7

Type of endocrine therapy

Tamoxifen 13 11.2 16 13.9

Letrozole 18 15.5 16 13.9

Anastrozole 8 6.9 8 7.0

Exemestane 6 5.2 5 4.3

Fulvestrant 0 0 1 0.9

Goserelin 6 5.2 12 10.4

Park et al

202.195.183.214

Information downloaded from jco.ascopubs.org and provided by at Nanjing Medical University on April 10, 2013 from

Table 4. Toxicities

Adverse Event

All Grades Grade 3-4

Before Random Assignment After Random Assignment Before Random Assignment After Random Assignment

Maintenance

(n 116)

Observation

(n 115)

Maintenance

(n 116)

Observation

(n 115)

Maintenance

(n 116)

Observation

(n 115)

Maintenance

(n 116)

Observation

(n 115)

No. % No. % No. % No. % No. % No. % No. % No. % P

Neutropenia 102 87.9 99 86.1 .82 101 87.1 35 30.4 .001 80 69.0 78 67.8 .57 71 61.2 1 0.9 .001

Thrombocytopenia 55 47.4 58 50.4 .55 30 25.9 14 12.2 .008 0 0 1 0.9 .50 1 0.9 0 0 .50

Anemia 106 91.4 109 94.8 .29 102 87.9 74 64.3 .001 3 2.6 6 5.2 .33 1 0.9 0 0 .50

Neuropathy 105 90.5 99 86.1 .31 104 89.7 87 75.7 .005 4 3.4 2 1.7 .68 4 3.4 2 1.7 .68

Azotemia 2 1.7 1 0.9 .62 5 4.3 0 0 .06 0 0 0 0 NA 5 4.3 0 0 .06

AST 69 69.5 68 59.1 .96 45 38.8 36 31.3 .23 0 0 0 0 NA 1 0.9 1 0.9 .10

ALT 72 62.1 71 61.7 .96 50 43.1 28 24.3 .003 4 3.4 2 1.7 .68 0 0 0 0 NA

Nausea 71 61.2 69 60.0 .89 51 44.0 22 19.1 .001 0 0 0 0 NA 0 0 0 0 NA

Vomiting 41 35.3 42 36.5 .89 27 23.3 5 4.3 .001 0 0 0 0 NA 0 0 0 0 NA

Constipation 26 22.4 32 27.8 .34 24 20.7 7 6.1 .001 0 0 0 0 NA 0 0 0 0 NA

Diarrhea 19 16.4 24 20.9 .38 19 16.4 1 0.9 .001 0 0 2 1.7 .25 1 0.9 1 0.9 .10

Abbreviation: NA, not assessable.

Before random assignment, all patients received six cycles of paclitaxel and gemcitabine chemotherapy.

Maintenance Paclitaxel/Gemcitabine for Metastatic Breast Cancer

202.195.183.214

Information downloaded from jco.ascopubs.org and provided by at Nanjing Medical University on April 10, 2013 from

benefit and improved PFS, the role of first-line chemotherapy and its

total duration may be critical determinants of OS, particularly in

patients with triple-negative tumors, for whom targeted therapeutic

strategies are urgently needed. Maintenance PG chemotherapy may

be a good therapeutic option in this setting.

In the maintenance group, 33 patients stopped the study drugs

without disease progression, and in this group, the median number of

chemotherapy cycles was 12 (range, nine to 26 cycles) in addition to

the initial six cycles of PG chemotherapy. The optimal number of

maintenance chemotherapy cycles should be individualized according

to each patient’s circumstance, although the median number of PG

chemotherapy cycles was six after random assignment in this study. It

seems unrealistic to subject all patients to 18 or more cycles of chemotherapy

in daily practice, although there was no documentation of

serious toxicity or definitive impairment of QoL. Obviously, the QoL

results should be reported in relation to the results from the primary

end point so that a full view of the risks and benefits of the maintenance

chemotherapy can be presented.

In conclusion, our results strengthen the data from a prior metaanalysis

showing the benefits of maintenance chemotherapy.12 This

study showed a clinically meaningful improvement in PFS and OS in

patients receiving maintenance PG chemotherapy for MBC.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS

OF INTEREST

Although all authors completed the disclosure declaration, the following

author(s) and/or an author’s immediate family member(s) indicated a

financial or other interest that is relevant to the subject matter under

consideration in this article. Certain relationships marked with a “U” are

those for which no compensation was received; those relationships marked

with a “C” were compensated. For a detailed description of the disclosure

categories, or for more information about ASCO’s conflict of interest policy,

please refer to the Author Disclosure Declaration and the Disclosures of

Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory

Role: None Stock Ownership: None Honoraria: Seock-Ah Im, Samyang

Corporation Research Funding: None Expert Testimony: None Other

Remuneration: None

AUTHOR CONTRIBUTIONS

Conception and design: Young-Hyuck Im

Administrative support: Young-Hyuck Im

Provision of study materials or patients: Yeon Hee Park, Joo Hyuk

Sohn, Young-Hyuck Im

Collection and assembly of data: Yeon Hee Park, Joo Hyuk Sohn,

Jungsil Ro, Jin-Hee Ahn, Sung-Bae Kim, Do Youn Oh, Sae-Won Han,

Soohyeon Lee, In Hae Park, Keun Seok Lee, Jee Hyun Kim, Seok Yun

Kang, Moon Hee Lee, Hee Sook Park

Data analysis and interpretation: Yeon Hee Park, Kyung Hae Jung,

Seock-Ah Im, Byung-Ho Nam, Jin Seok Ahn, Young-Hyuck Im

Manuscript writing: All authors

Final approval of manuscript: All authors

REFERENCES

1. Siegel R, Naishadham D, Jemal A: Cancer

statistics, 2012. CA Cancer J Clin 62:10-29, 2012

2. Thun MJ, Jemal A, Ward E: Global cancer incidence

and mortality, in DeVita VT Jr: Cancer: Principles

and Practice of Oncology (ed 9). Philadelphia, PA, Lippincott

Williams & Wilkins, 2011, pp 241-266

3. Ejlertsen B, Pfeiffer P, Pedersen D, et al:

Decreased efficacy of cyclophosphamide, epirubicin

and 5-fluorouracil in metastatic breast cancer when

reducing treatment duration from 18 to 6 months.

Eur J Cancer 29A:527-531, 1993

4. Muss HB, Case LD, Richards F 2nd, et al: Interrupted

versus continuous chemotherapy in patients with

metastatic breast cancer: The Piedmont Oncology Association.

N Engl J Med 325:1342-1348, 1991

5. Falkson G, Gelman RS, Pandya KJ, et al:

Eastern Cooperative Oncology Group randomized

trials of observation versus maintenance therapy for

patients with metastatic breast cancer in complete

remission following induction treatment. J Clin Oncol

16:1669-1676, 1998

6. Coates A, Gebski V, Bishop JF, et al: Improving

the quality of life during chemotherapy for advanced

breast cancer: A comparison of intermittent and continuous

treatment strategies.NEngl JMed317:1490-1495,

1987

7. Harris AL, Cantwell BM, Carmichael J, et al:

Comparison of short-term and continuous chemotherapy

(mitozantrone) for advanced breast cancer.

Lancet 335:186-190, 1990

8. Dixon AR, Jackson L, Chan SY, et al: Continuous

chemotherapy in responsive metastatic breast cancer: A

role for tumour markers? Br J Cancer 68:181-185, 1993

9. Gregory RK, Powles TJ, Chang JC, et al: A

randomised trial of six versus twelve courses of

chemotherapy in metastatic carcinoma of the

breast. Eur J Cancer 33:2194-2197, 1997

10. Nooij MA, de Haes JC, Beex LV, et al: Continuing

chemotherapy or not after the induction

treatment in advanced breast cancer patients: Clinical

outcomes and oncologists’ preferences. Eur J

Cancer 39:614-621, 2003

11. Gennari A, Amadori D, De Lena M, et al: Lack

of benefit of maintenance paclitaxel in first-line

chemotherapy in metastatic breast cancer. J Clin

Oncol 24:3912-3918, 2006

12. Gennari A, Stockler M, Puntoni M, et al: Duration

of chemotherapy for metastatic breast cancer: A systematic

review and meta-analysis of randomized clinical trials.

J Clin Oncol 29:2144-2149, 2011

13. O’Shaughnessy J, Miles D, Vukelja S, et al:

Superior survival with capecitabine plus docetaxel

combination therapy in anthracycline-pretreated patients

with advanced breast cancer: Phase III trial

results. J Clin Oncol 20:2812-2823, 2002

14. Albain KS, Nag SM, Calderillo-Ruiz G, et al:

Gemcitabine plus paclitaxel versus paclitaxel monotherapy

in patients with metastatic breast cancer

and prior anthracycline treatment. J Clin Oncol 26:

3950-3957, 2008

15. Chan S, Romieu G, Huober J, et al: Phase III

study of gemcitabine plus docetaxel compared with

capecitabine plus docetaxel for anthracyclinepretreated

patients with metastatic breast cancer.

J Clin Oncol 27:1753-1760, 2009

16. Therasse P, Le Cesne A, Van Glabbeke M, et

al: RECIST vs. WHO: Prospective comparison of

response criteria in an EORTC phase II clinical trial

investigating ET-743 in advanced soft tissue sarcoma.

Eur J Cancer 41:1426-1430, 2005

17. Eisenhauer EA, Therasse P, Bogaerts J, et al:

New response evaluation criteria in solid tumours:

Revised RECIST guideline (version 1.1). Eur J Cancer

45:228-247, 2009

18. Gennari A, D’Amico M, Corradengo D: Extending

the duration of first-line chemotherapy in

metastatic breast cancer: A perspective review.

Ther Adv Med Oncol 3:229-232, 2011

19. National Comprehensive Cancer Network:

NCCN Clinical Practice Guidelines in Oncology:

Breast Cancer (ed V. 2.2010). http://www.nccn.org/

professionals/physician_gls/f_guidelines.asp#site

20. Alba E, Ruiz-Borrego M, MargelíM, et al:

Maintenance treatment with pegylated liposomal

doxorubicin versus observation following induction

chemotherapy for metastatic breast cancer: GEICAM

2001-01 study. Breast Cancer Res Treat 122:

169-176, 2010

Support

Supported by Eli Lilly (Indianapolis, IN) for study drug (gemcitabine) and CJ Korea (Seoul, Korea) for research funding.

■ ■ ■

Park et al

202.195.183.214

Information downloaded from jco.ascopubs.org and provided by at Nanjing Medical University on April 10, 2013 from

Acknowledgment

Presented in part at the 48th Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2012, Chicago, IL.

We thank Min Young Son of the Korean Cancer Study Group for data management support and the study coordinators from each institute.

Maintenance Paclitaxel/Gemcitabine for Metastatic Breast Cancer

202.195.183.214

Information downloaded from jco.ascopubs.org and provided by at Nanjing Medical University on April 10, 2013 from

Unitrans世聯(lián)翻譯公司在您身邊,離您近的翻譯公司,心貼心的專業(yè)服務(wù),專業(yè)的全球語(yǔ)言翻譯與信息解決方案供應(yīng)商,專業(yè)翻譯機(jī)構(gòu)品牌。無論在本地,國(guó)內(nèi)還是海外,我們的專業(yè)、星級(jí)體貼服務(wù)，為您的事業(yè)加速！世聯(lián)翻譯公司在北京、上海、深圳等國(guó)際交往城市設(shè)有翻譯基地，業(yè)務(wù)覆蓋全國(guó)城市。每天有近百萬字節(jié)的信息和貿(mào)易通過世聯(lián)走向全球！積累了大量政商用戶數(shù)據(jù)，翻譯人才庫(kù)數(shù)據(jù)，多語(yǔ)種語(yǔ)料庫(kù)大數(shù)據(jù)。世聯(lián)品牌和服務(wù)品質(zhì)已得到政務(wù)防務(wù)和國(guó)際組織、跨國(guó)公司和大中型企業(yè)等近萬用戶的認(rèn)可。專業(yè)翻譯公司,北京翻譯公司,上海翻譯公司,英文翻譯,日文翻譯,韓語(yǔ)翻譯,翻譯公司排行榜,翻譯公司收費(fèi)價(jià)格表,翻譯公司收費(fèi)標(biāo)準(zhǔn),翻譯公司北京,翻譯公司上海。

上一篇：世聯(lián)翻譯公司完成技文化交流中心冊(cè)子中文翻譯
下一篇：世聯(lián)翻譯公司完成宣傳頁(yè)中文翻譯

收藏打印

“貴司提交的稿件專業(yè)詞匯用詞準(zhǔn)確，語(yǔ)言表達(dá)流暢，排版規(guī)范，且服務(wù)態(tài)度好。在貴司的幫助下，我司的編制周期得以縮短，稿件語(yǔ)言的表達(dá)質(zhì)量得到很大提升”

華東建筑設(shè)計(jì)研究總院
“我單位是一家總部位于丹麥的高科技企業(yè)，和世聯(lián)翻譯第一次接觸，心中仍有著一定的猶豫，貴司專業(yè)的譯員與高水準(zhǔn)的服務(wù)，得到了國(guó)外合作伙伴的認(rèn)可！”

世萬保制動(dòng)器（上海）有限公司
“我公司是一家荷蘭駐華分公司，主要致力于行為學(xué)研究軟件、儀器和集成系統(tǒng)的開發(fā)和銷售工作，所需翻譯的英文說明書專業(yè)性強(qiáng)，翻譯難度較大，貴司總能提供優(yōu)質(zhì)的服務(wù)。”

諾達(dá)思（北京）信息技術(shù)有限責(zé)任公司
“為我司在東南亞地區(qū)的業(yè)務(wù)開拓提供小語(yǔ)種翻譯服務(wù)中，翻譯稿件格式美觀整潔，能最大程度的還原原文的樣式，同時(shí)翻譯質(zhì)量和速度也得到我司的肯定和好評(píng)！”

上海大眾
“在此之前，我們公司和其他翻譯公司有過合作，但是翻譯質(zhì)量實(shí)在不敢恭維，所以當(dāng)我認(rèn)識(shí)劉穎潔以后，對(duì)她的專業(yè)性和貴公司翻譯的質(zhì)量非常滿意，隨即簽署了長(zhǎng)期合作合同�！�

銀泰資源股份有限公司
“我行自2017年與世聯(lián)翻譯合作，合作過程中十分愉快。特別感謝Jasmine Liu, 態(tài)度熱情親切，有耐心，對(duì)我行提出的要求落實(shí)到位，體現(xiàn)了非常高的專業(yè)性�！�

南洋商業(yè)銀行
“與我公司對(duì)接的世聯(lián)翻譯客服經(jīng)理，可以及時(shí)對(duì)我們的要求進(jìn)行反饋，也會(huì)盡量滿足我們臨時(shí)緊急的文件翻譯要求。熱情周到的服務(wù)給我們留下深刻印象！”

黑龍江飛鶴乳業(yè)有限公司
“翻譯金融行業(yè)文件各式各樣版式復(fù)雜，試譯多家翻譯公司，后經(jīng)過比價(jià)、比服務(wù)、比質(zhì)量等流程下來，最終敲定了世聯(lián)翻譯。非常感謝你們提供的優(yōu)質(zhì)服務(wù)�！�

國(guó)金證券股份有限公司
“我司所需翻譯的資料專業(yè)性強(qiáng)，涉及面廣，翻譯難度大，貴司總能提供優(yōu)質(zhì)的服務(wù)。在一次業(yè)主單位對(duì)完工資料質(zhì)量的抽查中，我司因?yàn)槎砦姆g質(zhì)量過關(guān)而受到了好評(píng)。”

中辰匯通科技有限責(zé)任公司
“我司在2014年與貴公司建立合作關(guān)系，貴公司的翻譯服務(wù)質(zhì)量高、速度快、態(tài)度好，贏得了我司各部門的一致好評(píng)。貴司經(jīng)理工作認(rèn)真踏實(shí)，特此致以誠(chéng)摯的感謝！”

新華聯(lián)國(guó)際置地（馬來西亞）有限公司
“我們需要的翻譯人員，不論是筆譯還是口譯，都需要具有很強(qiáng)的專業(yè)性，貴公司的德文翻譯稿件和現(xiàn)場(chǎng)的同聲傳譯都得到了我公司和合作伙伴的充分肯定�！�

西馬遠(yuǎn)東醫(yī)療投資管理有限公司
“在這5年中，世聯(lián)翻譯公司人員對(duì)工作的認(rèn)真、負(fù)責(zé)、熱情、周到深深的打動(dòng)了我。不僅譯件質(zhì)量好，交稿時(shí)間及時(shí)，還能在我司資金周轉(zhuǎn)緊張時(shí)給予體諒�！�

華潤(rùn)萬東醫(yī)療裝備股份有限公司
“我公司與世聯(lián)翻譯一直保持著長(zhǎng)期合作關(guān)系，這家公司報(bào)價(jià)合理，質(zhì)量可靠，效率又高。他們翻譯的譯文發(fā)到國(guó)外公司，對(duì)方也很認(rèn)可。”

北京世博達(dá)科技發(fā)展有限公司
“貴公司翻譯的譯文質(zhì)量很高，語(yǔ)言表達(dá)流暢、排版格式規(guī)范、專業(yè)術(shù)語(yǔ)翻譯到位、翻譯的速度非�？�、后期服務(wù)熱情。我司翻譯了大量的專業(yè)文件，經(jīng)過長(zhǎng)久合作，名副其實(shí)，值得信賴�！�

北京塞特雷特科技有限公司
“針對(duì)我們農(nóng)業(yè)科研論文寫作要求，盡量尋找專業(yè)對(duì)口的專家為我提供翻譯服務(wù)，最后又按照學(xué)術(shù)期刊的要求，提供潤(rùn)色原稿和相關(guān)的證明文件。非常感謝世聯(lián)翻譯公司！”

中國(guó)農(nóng)科院
“世聯(lián)的客服經(jīng)理態(tài)度熱情親切，對(duì)我們提出的要求都落實(shí)到位，回答我們的問題也非常有耐心。譯員十分專業(yè)，工作盡職盡責(zé)，獲得與其共事的公司總部同事們的一致高度認(rèn)可�！�

格萊姆公司
“我公司與馬來西亞政府有相關(guān)業(yè)務(wù)往來，急需翻譯項(xiàng)目報(bào)備材料。在經(jīng)過對(duì)各個(gè)翻譯公司的服務(wù)水平和質(zhì)量的權(quán)衡下，我們選擇了世聯(lián)翻譯公司。翻譯很成功，公司領(lǐng)導(dǎo)非常滿意�！�

北京韜盛科技發(fā)展有限公司
“客服經(jīng)理能一貫熱情負(fù)責(zé)的完成每一次翻譯工作的組織及溝通。為客戶與譯員之間搭起順暢的溝通橋梁。能協(xié)助我方建立專業(yè)詞庫(kù)，并向譯員準(zhǔn)確傳達(dá)落實(shí)，準(zhǔn)確及高效的完成統(tǒng)一風(fēng)格�！�

HEURTEY PETROCHEM法國(guó)赫銻石化
“貴公司與我社對(duì)翻譯項(xiàng)目進(jìn)行了幾次詳細(xì)的會(huì)談，期間公司負(fù)責(zé)人和廖小姐還親自來我社拜訪，對(duì)待工作熱情，專業(yè)度高，我們雙方達(dá)成了很好的共識(shí)。對(duì)貴公司的服務(wù)給予好評(píng)！”

東華大學(xué)出版社
“非常感謝世聯(lián)翻譯！我們對(duì)此次緬甸語(yǔ)訪談翻譯項(xiàng)目非常滿意，世聯(lián)在充分了解我司項(xiàng)目的翻譯意圖情況下，即高效又保質(zhì)地完成了譯文。”

上海奧美廣告有限公司
“在合作過程中，世聯(lián)翻譯保質(zhì)、保量、及時(shí)的完成我們交給的翻譯工作�？蛻艚�(jīng)理工作積極，服務(wù)熱情、周到，能全面的了解客戶的需求，在此表示特別的感謝�！�

北京中唐電工程咨詢有限公司
“我們通過圖書翻譯項(xiàng)目與你們相識(shí)乃至建立友誼，你們報(bào)價(jià)合理、服務(wù)細(xì)致、翻譯質(zhì)量可靠。請(qǐng)?jiān)试S我們借此機(jī)會(huì)向你們表示衷心的感謝！”

山東教育出版社
“很滿意世聯(lián)的翻譯質(zhì)量，交稿準(zhǔn)時(shí)，中英互譯都比較好，措辭和句式結(jié)構(gòu)都比較地道，譯文忠實(shí)于原文。TNC是一家國(guó)際環(huán)保組織，發(fā)給我們美國(guó)總部的同事后，他們反應(yīng)也不錯(cuò)。”

TNC大自然保護(hù)協(xié)會(huì)
“原英國(guó)首相布萊爾來訪，需要非常專業(yè)的同聲傳譯服務(wù)，因是第一次接觸，心中仍有著一定的猶豫，但是貴司專業(yè)的譯員與高水準(zhǔn)的服務(wù)，給我們留下了非常深刻的印象�！�

北京師范大學(xué)壹基金公益研究院
“在與世聯(lián)翻譯合作期間，世聯(lián)秉承著“上善若水、厚德載物”的文化理念，以上乘的品質(zhì)和質(zhì)量，信守對(duì)客戶的承諾，出色地完成了我公司交予的翻譯工作�！�

國(guó)科創(chuàng)新（北京）信息咨詢中心
“由于項(xiàng)目要求時(shí)間相當(dāng)緊湊，所以世聯(lián)在保證質(zhì)量的前提下，盡力按照時(shí)間完成任務(wù)。使我們?cè)谑啦⿻?huì)俄羅斯館日活動(dòng)中準(zhǔn)備充足，并受到一致好評(píng)�！�

北京華國(guó)之窗咨詢有限公司
“貴公司針對(duì)客戶需要，挑選優(yōu)秀的譯員承接項(xiàng)目，翻譯過程客戶隨時(shí)查看中途稿，并且與客戶溝通術(shù)語(yǔ)方面的知識(shí)，能夠更準(zhǔn)確的了解到客戶的需求，確保稿件高質(zhì)量。”

日工建機(jī)（北京）國(guó)際進(jìn)出口有限公司

日韩亚洲欧美色图,久久亚洲精精品中文字幕,国产，日韩，欧美综合在线,丰满少妇2中文免费观看,国产精品一区二区20P发布,我强进了老师身体在线观看

世聯(lián)翻譯公司完成醫(yī)學(xué)英文翻譯