Original Article · Originalarbeit
Forsch Komplementmed 2011;18:77–83
DOI: 10.1159/000327306
Efficacy and Safety of Rhus verniciflua Stokes
Extracts in Patients with Previously Treated Advanced
Non-Small Cell Lung Cancer
Seong Ha Cheona Kyung Seok Kimb Sehyun Kimc Hyun Sik Jungb Won Cheol Choib
Wan Kyu Eoa
a
Department of Internal Medicine, M=+ Integrative Cancer Center, East West Neo Medical Center, Kyung Hee University College of Medicine,
b
Department of Oriental Oncology, M=+ Integrative Cancer Center, East West Neo Medical Center, Kyung Hee University College
of Oriental Medicine,
c
Graduate School of East West Medical Science, Kyung Hee University, Seoul, Korea
Keywords
Allergen-removed Rhus verniciflua Stokes extract ·
Advanced non-small cell lung cancer ·
Previously treated · Herbal medicine · Lacquer tree
Summary
Background: Systemic treatments for advanced non-small cell
lung cancer (NSCLC) have modest survival benefits but high
toxicity. Rhus verniciflua Stokes (RVS), the lacquer tree, is an
ancient traditional medicine being used for the treatment of
cancer. We investigated the efficacy and safety of allergen-
removed RVS extract (aRVS) for the prolongation of survival in
NSCLC after the failure of first-line or second-line chemo-
therapy. Patients and Methods: We reviewed the medical
records of 40 patients who were treated with aRVS for previ-
ously treated, advanced NSCLC at the M=μ Integrative Cancer
Center, Korea, between June 2006 and June 2009. The primary
objective of this study was to assess overall survival. Second-
ary objectives included assessments of disease control rates,
progression-free survival, and the safety of aRVS treatment.
Results: The median survival time was 8.4 months with a 1-year
survival of 40%. The disease control rate was 63.6%, and the
median progression-free survival interval was 3.9 months. Pa-
tients who had better performance status and adenocarcinoma
experienced more favorable outcomes in terms of overall sur-
vival. Toxicities in aRVS treatment were negligible, with the
most common drug-related adverse events being mild epi-
gastric pain and itching skin. Hematologic toxicity was absent.
Conclusions: Survival data and favorable levels of tolerability
suggest the potential of aRVS treatment in previously treated
patients with advanced NSCLC. Treatment with aRVS might be
a viable alternative in patients for whom chemotherapy is not
feasible, or who refuse chemotherapy.
© 2011 S. Karger GmbH, Freiburg
1661-4119/11/0182-0077$38.00/0
Fax +49 761 4 52 07 14
Information@Karger.de Accessible online at:
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Published online: April 4, 2011
Schlüsselwörter
Allergenbereinigter Rhus verniciflua-Stokes-Extrakt ·
Fortgeschrittenes nichtkleinzelliges Lungenkarzinom ·
Vorbehandelt · Phytomedizin · Lackbaum
Zusammenfassung
Hintergrund: Die systemische Behandlung des fortgeschritte-
nen nichtkleinzelligen Lungenkarzinoms (NSCLC) ist mit einem
geringfügigen Überlebensvorteil und starker Toxizität verbun-
den. Rhus verniciflua-Stokes (RVS), der Lackbaum, ist eine alte
traditionelle Medizin, die zur Krebsbehandlung eingesetzt wird.
Wir haben die Effizienz und Sicherheit von allergenbereinigtem
RVS-Extrakt (aRVS) hinsichtlich der Verlängerung des Über-
lebens von NSCLC-Patienten nach Versagen der Erst- oder
Zweitlinienchemotherapie untersucht. Patienten und Metho-
den: Die Unterlagen von 40 Patienten mit vorbehandeltem fort-
geschrittenen NSCLC, die im M=μ Integrative Cancer Center,
Korea, zwischen Juni 2006 und Juni 2009 mit aRVS behandelt
worden waren, wurden untersucht. Das primäre Ziel dieser Stu-
die war es, das Gesamtüberleben zu bewerten. Sekundäre Ziele
waren die Beurteilung der Krankheitskontrollrate, des progres-
sionsfreien Überlebens und der Sicherheit der Behandlung mit
aRVS. Ergebnisse: Das mittlere Überleben war 8,4 Monate und
die 1-Jahres-Überlebensrate 40%. Die Krankheitskontrollrate
betrug 63,6% und das mittlere progressionsfreie Überlebens-
intervall 3,9 Monate. Patienten mit einem besseren Perfor-
mance-Status und einer Adenokarzinomdiagnose hatten ein
besseres Outcome in Hinsicht auf das Gesamtüberleben. Die
mit der aRVS-Behandlung verbundenen Toxizitäten waren ver-
nachlässigbar; am häufigsten wurden milde epigastrische
Schmerzen und Hautjucken beobachtet. Hämatologische Toxi-
zitäten traten nicht auf. Schlussfolgerungen: Die Überlebensda-
ten und die gute Toleranz der aRVS-Behandlung deuten auf
deren Potential bei vorbehandelten Patienten mit fortgeschritte-
nem NSCLC hin. Die aRVS-Behandlung könnte eine realistische
Alternative für diejenigen Patienten sein, die keine Kandidaten
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Wan Kyu Eo, MD, PhD
Division of Hemato-Oncology
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Department of Internal Medicine, M×μ Integrative Cancer Center
East West Neo Medical Center, Kyung Hee University College of Medicine
149 Sangil-dong, Gangdong-gu, 130–090 Seoul, Republic of Korea
Tel. +82 2 440 62-76, Fax -96, zzidol@khnmc.or.kr
Introduction
Advanced non-small cell lung cancer (NSCLC) is an incurable
disease with treatment being primarily palliative [1]. The cur-
rent standard first-line treatment for NSCLC consists of plati-
num-based combination chemotherapy, with a 7–12-month me-
dian survival [2–7]. If patients fail first-line chemotherapy, the
options available for salvage therapy are limited. In the second-
line setting, docetaxel, erlotinib, and pemetrexed are approved
with equivalent efficacy, but with different safety parameters
[8–10]. Despite improvements in chemotherapy regimens over
the last decade, previously treated NSCLC consistently has a
poor prognosis with a median survival of 5–8 months, and a
1-year survival of 30–40%. These patients inevitably experi-
ence tumor progression [8–15]. Moreover, there exists no de-
fined role for chemotherapy in NSCLC patients who have
failed 2 or more prior chemotherapy regimens [16]. Since most
patients in this group have poor performance status, they may
not be amenable to further chemotherapy. Therefore, a novel
therapeutic drug with less toxicity is required to improve sur-
vival and quality of life for previously treated NSCLC patients.
In Korea, herbal medicine is sometimes combined with
chemotherapy for the treatment of cancer. Some herbal medi-
cines have been reported to increase the efficacy of chemo-
therapy and to reduce toxicity [17, 18]. However, the putative
benefits of herbal medicine for advanced NSCLC have not yet
been adequately tested. Most studies suffer from poor quality
of reporting, undefined characteristics of patients, as well as
an inaccurate cancer status for each patient [17]. Rhus vernici-
flua Stokes (RVS), the lacquer tree, is an indigenous East
Asian plant that has been used as an anti-cancer treatment in
traditional Korean medicine since the 15th century [19–22].
Preclinical studies demonstrated that RVS extract exhibits
anti-proliferative and apoptotic activities in human cancer cell
lines via activation of caspase-9 and inhibition of the PI3K-
Akt/PKB pathway, as well as anti-oxidant effects [23–26].
Furthermore, RVS extracts have been shown to inhibit the
expression of vascular endothelial growth factor (VEGF) [27].
These and other accumulated clinical data indicate that RVS
extracts may have clinical applications in cancer patients [21,
28]. However, there are no reports on single agent RVS ex-
tracts as possible treatment option for NSCLC except 1 anec-
dotal case study [22]. Therefore, the aim of our study was to
Fig. 1. Study
schedule. CTx =
Chemotherapy;
NSCLC = non-small
cell lung cancer;
PD = progressive
disease.
78 Forsch Komplementmed 2011;18:77–83
assess the safety of allergen-removed RVS extract (aRVS)
and to determine its efficacy with respect to overall survival
and progression-free survival in patients with previously
treated NSCLC. We also investigated the prognostic factors
associated with survival.
Patients and Methods
This retrospective study was approved by the East-West Neo Medical
Center, Kyung Hee University (KHNMC) Institutional Review Board.
All patients signed a written informed consent for participation in the
study.
Patients
Between June 2006 and June 2009, we assessed 40 patients who met the
following inclusion criteria among the patients treated for NSCLC at the
M=+ Integrative Cancer Center (M=+ ICC), KHNMC, Korea. This study
included patients with locally advanced or metastatic NSCLC, who had
progressed after 1 or 2 prior chemotherapy regimen (fig. 1). Patients were
eligible if they were 18 years or older, and if they had histologically or
cytologically confirmed locally advanced or metastatic NSCLC (inopera-
ble stage IIIB or stage IV). Additionally, these patients were eligible if
they had Eastern Cooperative Oncology Group (ECOG) performance
status 0–2, if they had measurable or evaluable disease by Response Eval-
uation Criteria in Solid Tumors (RECIST), and if they had adequate
bone marrow, hepatic, and renal function. Patients who had central nerv-
ous system (CNS) metastasis were also eligible. We excluded those pa-
tients who visited the hospital simply for counseling without taking aRVS.
We also excluded those patients with coexisting malignancies.
Evaluation of Clinical and Tumor Characteristics
The following demographic and clinicopathological information was
retrospectively obtained from reviews of the medical records in the M=+
ICC, KHNMC, Korea: age, gender, performance status, smoking history,
tumor histology, treatment regimens (aRVS alone or aRVS with chemo-
therapy), status of primary NSCLC and metastatic site, history of previ-
ous therapy including time and response. We defined refractory as tumor
progression during treatment or within 3 months of chemotherapy com-
pletion. NSCLC staging was determined according to American Joint
Committee on Cancer criteria (6th edition, 2002).
Study Drug, Allergen-Removed Rhus verniciflua Stokes Extract
Because the urushiol in RVS causes contact sensitivity, urushiol-free RVS
extract is used in the M=+ ICC. The extract was manufactured as follows
(manufactured by Kyung Hee University Medical Center according to
the method described in Korean Patent No. 0504160): Rhus verniciflua
Stokes stalk, which was 10 years old and grown in Wonju, Republic of
Korea, was dried without direct sunlight contact, and chopped. The
chopped pieces were roasted in an iron pot at 240 °C for 50 min to re-
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Table 1. Patient baseline characteristics Table 1. Continued

Patients, n (%) Patients, n (%)

Gender Metastatic site

Male 21 (52.5) Brain 12 (40.0)
Female 19 (47.5) Lung to lung 19 (47.5)
Age (median age (range) = 58 (35–74) years) Bone 10 (25.0)
< 65 years 29 (72.5) Liver 3 (7.5)
* 65 years 11 (27.5) Adrenal gland 2 (5.0)
Performance status Pleural effusion 11 (27.5)
ECOG 0 0
ECOG = Eastern Cooperative Oncology Group; aRVS = allergen-
ECOG 1 23 (57.5)
removed Rhus verniciflua Stokes extracts; PD = progressive disease;
ECOG 2 17 (42.5)
PR = partial response; SD = stable disease.
Smoking status
Current smoker or ever smoked 17 (42.5)
Never smoked 23 (57.5)
move allergens, and extracted 2 times with 10-fold volume of water at
Tumor histology 90–95 °C for 6 h. The extracts were filtered with Whatman Grade GF/B
Adenocarcinoma 26 (65.0) Glass Microfiber filter paper and concentrated under vacuum to remove
Non-adenocarcinoma 7 (17.5) water. The concentrate was lyophilized to a brownish powder. The ex-
Not recorded 7 (17.5) traction yield from 100 g of chopped stalks was 3.3 g. The quality of the
Treatment modality extract was tested and controlled according to the guidelines of the
aRVS alone 23 (57.5) Korean Food and Drug Administration (KFDA), and high performance
aRVS with chemotherapy 17 (42.5) liquid chromatography showed that the RVS extract contained fustin,
Disease stage at initial diagnosis fisetin, sulfuretin, butein, and other compounds. The content of fustin and
I 1 (2.5) fisetin was more than 13% (w/w) and 2% (w/w), respectively.
II 1 (2.5)
IIIa 1 (2.5) Treatment
IIIb 11 (27.5) All patients received an initial dose of aRVS 1,350 mg/day (450 mg 3 times
daily) orally. The recommended dose for aRVS for this study is based on
IV 24 (60.0)
the 11 ancient medical books approved by The Korean Food and Drug
Not recorded 2 (5.0)
Administration (KFDA) and data from preclinical observations [29].
Time from diagnosis to RVS treatment
aRVS was administered daily unless there was evidence of disease pro-
< 6 months 13 (32.5) gression or intolerance to the study treatment. Patients who wanted to
6–12 months 19 (47.5) continue aRVS despite progressive disease (PD) were maintained on
> 12 months 8 (20.0) aRVS. Concurrent combined chemotherapy went ahead as planned until
Current disease status disease progression, unacceptable toxicity, or the patient’s withdrawal.
Recurrent 6 (15.0) Patients were allowed to receive temporary concomitant supportive care
Locally advanced or metastatic 34 (85.0) therapies including acupuncture, moxibustion, and intermittent use of
Time since last chemotherapy other herbal medicine for symptom palliation during aRVS treatment.
< 3 months 31 (77.5)
* 3 months 9 (22.5) Assessment of Toxicity and Tumor Response
Prior chemotherapy Toxicity was analyzed according to the Common Terminology Criteria
1 regimen 23 (57.5) for Adverse Events (CTCAE) version 3.0. only for patients treated with
2 regimens 17 (42.5) aRVS alone to avoid confounders such as toxic effects of chemotherapy.
Tumor responses were measured by using the RECIST criteria version
Platinum-based therapy 23 (57.5)
1.0 every 6–8 weeks [30].
Refractory to first-line chemotherapy
Refractory 33 (82.5)
Endpoints and Statistics
Received (not refractory) 7 (17.5) The primary endpoint of this study was overall survival (OS) with second-
Best response to first-line chemotherapy ary endpoints that included disease control rate, progression-free sur-
PR/SD 25 (62.5) vival, and safety. OS time (in months) was defined as time from the first
PD 15 (37.5) day of treatment with aRVS to time of death from any cause. When death
Prior radiation 19 (47.5) was not observed for a patient either because the patient was known to be
Prior radiation organ (n = 19) alive at the end of the study or the patient was lost to follow-up, the sur-
Brain 10 (52.6) vival time of this patient is said to be censored. Censored survival time (in
Bone 5 (26.3) months) was defined as time from the start of aRVS to the end of the
Lung 4 (21.1) study or the last day of follow-up.
Number of metastatic site Progression-free survival time (in months) was the time from the first
0 8 (20.0) day of treatment with aRVS to the date of first documentation of disease
1 16 (40.0) progression, or death from any cause, whichever came first. Documenta-
tion of progression must be by objective disease assessment. Patients last
2 14 (35.0)
known to be alive and to be progression-free, and who had a baseline and
3 or more 2 (5.0)
at least 1 on-study disease assessment, are censored at the date of the last
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Cell Lung Cancer

Fig. 2. Overall survival and progression-free
survival curves of all patients. aRVS = Allergen-
removed Rhus verniciflua stokes extract.
objective disease assessment that verified lack of disease progression. Pa-
tients with no on-study disease assessments were censored at the first day
of treatment with aRVS unless death occurred prior to the first planned
assessment (in which case death is an event). Patients with documentation
of progression or death after an unacceptably long interval (> 9 weeks)
since the last tumor assessment were censored at the time of the last ob-
jective assessment prior to the event. OS and progression-free survival
were calculated with the Kaplan-Meier method, and statistically com-
pared between treatment modalities (aRVS alone vs. aRVS plus chemo-
therapy) using the log-rank test. Descriptive statistics were reported as
proportions and medians. Exploratory forward stepwise regression analy-
ses with the use of the Cox model were performed to adjust for treatment
effect and to identify prognostic factors for survival. Candidate covariates
included age (65 years or less vs. more than 65 years), sex, performance
status (ECOG 0 or 1 vs. ECOG 2), tumor histology (adenocarcinoma vs.
others), number of previous chemotherapy regimens (1 vs. 2), treatment
modality (aRVS alone vs. aRVS plus chemotherapy). All statistical analy-
ses were conducted using SPSS 16.0 statistical software (SPSS Inc., Chi-
cago, IL, USA). A p value of less than 0.05 was considered statistically
significant.
Results
Clinicopathologic Characteristics of Patients
Patient demographics and clinicopathologic characteristics are
summarized in table 1. The median age was 58 years (range
35–74). 28% of the patients were over 65 years. 43% had an
ECOG performance status of 2, and 65% were diagnosed with
adenocarcinoma. 43% received combined aRVS and chemo-
therapy. 43% had received 2 prior chemotherapy regimens.
83% of patients were refractory to first-line chemotherapy
regimen, and 40% had brain metastases.
80 Forsch Komplementmed 2011;18:77–83
Treatment Administered
aRVS was given for a median duration of 75 (range 7–714)
days, at a median dose of 1,270 (range 450–2,576) mg/day.
Patients with aRVS alone and aRVS in combination with
chemotherapy received aRVS for a median duration of 75
(range 7–415) days and 107 (range 19–714) days, respectively.
Eleven (27.5%) patients continued aRVS in spite of progres-
sion of disease.
Toxic Effects
Toxicities were evaluated only in 23 patients who received
aRVS alone. Most patients treated with aRVS alone tolerated
it well with no grade 3 or 4 adverse events. The most common
grade 1 or 2 adverse event was anorexia (4 patients, 18.2%)
followed by nausea, constipation, insomnia, febrile sensation
(1 patient each, 4.5%). There were no abnormal laboratory
values such as aspartate transaminase (AST), alanine
transaminase (ALT), and creatinine except one grade 1 AST/
ALT elevation. Neutropenia and thrombocytopenia were all
absent in these patients. There were no withdrawals or deaths
due to drug-related adverse events with aRVS.
Response and Survival
Of the 40 patients who received aRVS, 18 (45%) patients did
not have a scan for response evaluation. Eleven patients
dropped out before response evaluation. Among these early
drop-out patients, 2 patients died early, and 9 patients discon-
tinued study treatment without an apparent reason. The re-
maining 7 patients did not want regular scans for tumor
response although they received aRVS. Of the 22 who did
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Table 2. Cox’s proportional hazard analysis of prognostic factors for overall survival
Variable
Sex (female vs. male)
Age (<65 years vs. *65 years)
ECOG (0.1 vs. 2)
Tumor histology (adenocarcinoma vs. non-adenocarcinoma)
Previous regimens treated (1 vs. 2)
Treatment modality (aRVS alone vs. aRVS + chemotherapy)
ECOG = Eastern Cooperative Oncology Group; aRVS = allergen-removed Rhus verniciflua Stokes extract.
undergo response evaluation, 1 (4.5%) had partial response
(PR), 13 (59.1%) had stable disease (SD), and 8 (36.4%) had
PD. The disease control rate (DCR) was therefore 63.6%. In
the aRVS alone group, the rates of PR and SD were 0 and
66.7%, respectively. In the group with aRVS in combination
with chemotherapy, the rates of PR and SD were 7.7 and
53.8%, respectively, but these responses were not externally
validated. At the time of analysis, 38 deaths had occurred.
Figure 2 shows Kaplan-Meier curves for OS and progression-
free survival for the total 40 patients treated with aRVS. The
median OS was 8.4 months, and median progression-free sur-
vival was 3.9 months. Median OS in patients who had been
treated with 1 prior regimen was 7.8 months, and with 2 prior
regimens 8.9 months (p = 0.987). Median OS in aRVS alone
was 7.0 months and in aRVS plus chemotherapy it was 13.5
months. No statistically significant difference in OS was de-
tected between the aRVS alone group and aRVS in combina-
tion with chemotherapy (p = 0.622, 95% confidence interval
(CI) 0.367–1.821) using the stratified long-rank test. In the
Cox model, performance status ECOG 0 or 1 (p = 0.003, 95%
CI 0.093–0.609) and adenocarcinoma (p = 0.024, 95% CI
0.154–0.879) were associated with longer survival (table 2).
Discussion
The majority of patients with NSCLC are diagnosed at an ad-
vanced stage (IIIB/IV) [31]. Unfortunately, the progression of
this cancer is inevitable and therapeutic options in the second-
line setting and beyond are quite limited. These cases with ad-
vanced stages (IIIB or IV) cannot be cured with current ther-
apies. Thus, prolongation of survival and symptom palliation
are the main goals of treatment for these patients [1].
Docetaxel, pemetrexed, and erlotinib are agents known to
prolong survival among patients with disease progression
after cisplatin-based chemotherapy for NSCLC [8–10, 15].
Response rate, progression-free survival, and median survival
time of each agent are presented in table 3. However, few op-
tions are available, and the efficacy of salvage chemotherapy
still remains controversial for the treatment of patients with
disease progression after second-line chemotherapy. Also,
those patients who are not eligible for second-line chemother-
Rhus verniciflua Stokes Extracts in Non-Small
Cell Lung Cancer
Coefficient Standard error Hazard ratio 95% CI p value
0.101 0.381 1.107 0.524–2.336 0.790
0.264 0.440 1.302 0.550–3.081 0.549
–1.435 0.479 0.238 0.093–0.609 0.003
–1.000 0.445 0.368 0.154–0.879 0.024
–0.066 0.395 0.936 0.431–2.032 0.867
0.201 0.409 0.818 0.367–1.821 0.622
apy due to comorbidity, poor performance status, old age,
toxicity of previous chemotherapy, or patient’s refusal of
chemotherapy have limited treatment options. These patients
have been historically excluded from large randomized clini-
cal trials, and thus limited evidence-based data are available
to guide the treatment of these patients. As a result, the
search for new therapeutic strategies is motivated not only by
the need to improve survival rates, but also by the desire to
reduce toxicity, decrease symptoms, and improve the quality
of life of this patient population. There have been several per-
vious reports evaluating the efficacy of herbal medicine, but
most were tested in vitro only and only poorly defined the
characteristics of patients and primary cancers [17, 18, 32–35].
The drug assessed in this study is a standardized, quality-con-
trolled herbal medicine. However, the medical application of
RVS itself used to be limited because it contains a toxic allergen,
urushiol. Therefore, urushiol-removed RVS extract was devel-
oped. Based on the traditional medical literature, preclinical and
abundant clinical observations, aRVS has been prescribed pri-
marily for cancer patients who are refractory, or ineligible to
systemic chemotherapy due to comorbidity, poor performance
status, old age, or patient preference for our integrative cancer
center. aRVS is attractive in that it has little, if any, toxicity.
Specifically, no hematologic toxicity was encountered.
Though interaction of aRVS and chemotherapy has not been
unknown, combined aRVS and chemotherapy showed a median
survival time of 13.5 months, in spite of 23.5% of patients hav-
ing an ECOG performance status of 2 and 35.3% having had
previous second-line chemotherapy. aRVS rarely inhibited cy-
tochrome (CYP) P3A4 and CYP2D6 which are major human
CYP enzymes metabolizing a large majority of currently known
drugs [36]. Some preclinical and clinical studies have shown syn-
ergy between herbal medicine and chemotherapy in the treat-
ment of locally advanced or metastatic NSCLC, with a favora-
ble tolerability profile [17, 18]. However, because the synergistic
mechanism and the true positive interaction have not been
identified, it is possible that herbal medicine could produce det-
rimental drug-herb interactions when combined with chemo-
therapy. Further research regarding the interaction of aRVS
with a variety of chemotherapy regimens is warranted [37–39].
In this study, we evaluated the efficacy and safety of aRVS
in previously treated patients with NSCLC. The OS of 8.4
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 1-year survival
months was comparable to that of previously reported studies
that used second-line treatment regimens for NSCLC (table
3) [8–11, 13–15]. Additionally, this study drug was extremely
rate,%

well tolerated. It should be noted that our enrolled patients

22.5
37
19
32
19
30
30

35
31

40
27
21
32
had been extensively previously treated, and had poor per-
formance status. 43% of patients were receiving aRVS as a
Median survival

aRVS = Allergen-removed Rhus verniciflua Stokes extracts; Adeno = adenocarcinoma; BSC = best supportive care; CR = complete response; NSCLC = non-small cell lung cancer;
third-line treatment, and 43% had an ECOG performance
time, months

status of 2. Therefore, the results of this report support the

safety and efficacy of aRVS with or without chemotherapy for
7.5
4.6
5.7
5.6
8.3
7.9

8.0
6.7
4.7

8.4
5.6
5.1
7.6
the treatment of patients who have been extensively previ-
3.0 (TTTF) ously treated with chemotherapy.
2.6 (TTTF) Exploratory multivariate analyses showed that perform-
PFS/TTP,

2.0 (TTP)
1.8 (TTP)
2.9 (PFS)
1.6 (PFS)

2.9 (PFS)
2.9 (PFS)

2.7 (PFS)
2.2 (PFS)
1.8 (PFS)

3.9 (PFS)
2.2 (PFS)
months

ance status ECOG 0 or 1 and adenocarcinoma were signifi-

cant independent predictors of survival. Schiller et al. [4] and
Hanna et al. [10] also reported that performance status was an
important prognostic factor for survival. Although chemo-
9.1 (RR)
8.8 (RR)

7.6 (RR)
9.1 (RR)
DCR,%

therapy in combination with aRVS did not affect patient sur-

52.8

42.7
31.8

0.9

63.6

vival in the Cox model, aRVS in combination with chemo-

–

45

40
32

therapy showed better trends of survival. However, this result

Number of previous

does not mean much because of the small sample size. We

chemoregimens, %

1:80, 2:12.7, * 3:7.3

1:84.4, 2:15.3, 3:0.3

1:81.1, 2:15, * 3:9

1:80.2, 2:16.8, 3:0

1:49, 2:50, * 3 :1

rarely encountered toxic effects of aRVS. Moreover, there are

1:49, 2:50, * 3:1
1:50.6, * 2:49.4
1:50.2, * 2:49.8

1:46.9, 2 :53.1

no hematologic, renal and liver toxicities.

1:74, 2:26
1:71, 2:29
1:100, 2:0
1:100, 2:0

This study has several limitations. Most notably, the study

PFS = progression-free survival; RR = response rate; TTTF = time to treatment failure; TTP = time to progression.

was designed to be descriptive and exploratory. As a result,

there was no direct comparison condition and no obvious his-
torical control for evaluation of response rate or survival.
65.6 / 25.8 / 8.6
68.4 / 23.0 / 8.6
74.5 / 25.5 / 0

88.6 / 11.4 / 0
87.6 / 12.4 / 0

88.5 / 11.5 / 0
57.5 / 42.5 / 0
88.3 / 11.7 / 0
ECOG 0 or

Moreover, enrolled patients’ characteristics were somewhat

75 / 25.0 / 0
82 / 18 / 0
85 / 15 / 0

66 / 29 / 5
69 / 26 / 5
1/2/3, %

heterogeneous with respect to combination of chemotherapy.

There were too many patients who did not receive response
Table 3. Comparison of reports regarding variable treatment regimen for pretreated NSCLC

evaluation for NSCLC. This might overestimate the disease

Adeno,%

control rate. This lack of response evaluation occurred be-

cause some patients desired herbal medicine but did not want
54.4
49.3

57.0
50.4
49.0

65.0
56.2
NA
NA
56
52

48
48

to undergo examinations for evaluating the cancer status. De-

spite these limitations, aRVS was well tolerated as salvage
Median age,

therapy for extensively previously treated or poor perform-

ance status patients with NSCLC. This approach provides a
years

61
61
59
60
59
57

60
62
59

58
62
61
61

reasonable alternative for previously treated or less fit pa-

tients with NSCLC. Although further investigation will be
Patients, n

required to determine whether this therapy can be applied

1,129

safely and effectively to extensively previously treated pa-

55
100
125
123
283
288

733
488
243

40
563
733

tients with NSCLC, the availability of aRVS in the NSCLC

setting may help to prolong survival. In conclusion, this study
vinorelbine or ifosfamide

aRVS + chemotherapy

indicates that this regimen is a feasible treatment for exten-

docetaxel 75 mg/m2

docetaxel 75 mg/m2

docetaxel 75 mg/m2

sively previously treated patients with advanced NSCLC.

However, with the limited number of patients treated in this
pemetrexed

study, firm conclusions cannot be made and further ran-

docetaxel
Regimen

erlotinib

gefitinib

gefitinib

domized phase II and III studies need to be performed to

BSC

BSC

BSC

weigh the risks and benefits of aRVS especially for previously

treated patients with NSCLC.
INTEREST [13]

Current study
TAX320 [15]
TAX317 [9]

JEMI [10]

ISEL [12]
BR.21 [8]

Disclosure Statement
Study

The authors declared no conflict of interest.

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82 Forsch Komplementmed 2011;18:77–83 Cheon/Kim/Kim/Jung/Choi/Eo

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