Shinshu M ed J, 59 ⑸ :321〜325, 2011

Complete Response to S‑1 Monotherapy Over 3 Years in
an Elderly Patient with Advanced Non‑Small‑Cell Lung Cancer
Kazuhisa URUSHIHATA ＊, Toshihiko AGATSUMA , Toshiki YOKOYAMAMichiko ITOU , Keishi KUBO , Tomonobu KOIZUMI and Hisashi SHIMOJO
1） First Department of Internal Medicine, Shinshu University School of Medicine
2） Comprehensive Cancer Center, Shinshu University School of Medicine
3） Department of Laboratory Medicine, Shinshu University School of Medicine

The number of elderly patients with cancer continues to increase.The optimal chemotherapeutic regimenfor inoperable non‑small‑cell lung cancer (NSCLC)in elderly patients, especially over 80 years old, remains
controversial.S‑1,a newly developed oral ﬂuorouracil antitumor drug,has been reported to be eﬀective in thetreatment of gastrointestinal and pancreatic tumors and/or NSCLC. We experienced a case of an elderly
patient with advanced‑stage NSCLC who responded well to S‑1 monotherapywith tolerable toxicities and has
had three years of disease‑free survival. S‑1 appears to have signiﬁcant activity with mild toxicities forselected elderly NSCLC patients and in our view warrants further clinical study. Shinshu Med J 59 : 321―
325, 2011(Received for publication March 28, 2011;accepted in revised form June 6, 2011)
Key words:chemotherapy, elderly, lung cancer

elderly population, especially the patients over 80

Introduction

years old.

Lung cancer is the leading cause of cancer‑

S‑1 (Taiho Pharmaceutical Co.,Tokyo,Japan)isrelated deaths in Japan and throughout the Westerna novel oral ﬂuoropyrimidine derivative consistingworld .Approximately 50% of patients diagnosedof tegaful and two modulators, 5‑choloro2, 4‑dihy-with or dying from non‑small‑cell lung cancer

droxypyridine and potassium oxonate, in a molar(NSCLC)are 70 years or older around the world.

ratio of 1:0.4:1.S‑1 has been available for several

In general, doublet combinations of platinum com-solid malignancies including gastric cancer,pancre-

pounds are standard regimens as ﬁrst‑line treat-

atic cancer and NSCLC.In this report,we describe

ment in advanced‑stage NSCLC. There are aa case of advanced NSCLC aged 80 years, who

number of platinum‑based clinical trials;however,showed complete response to S‑1 monotherapy andonly 13‑17% of patients over 70 years old wereprolonged disease‑free survival for 3 years.

enrolled in these studies . In addition, it has notbeen demonstrated that platinum‑containing regi-

Case reportmens could actually increase the survival in elderly

An 80‑year‑old man presented with a two‑monthpatients with advanced NSCLC.Thus,the eﬀective

history of exertional dyspnea and anterior chest

treatment options for elderlypatients are extremely

pain during sleeping for the previous two months.

limited because of the lack of clinical trials for theHe visited our hospital in January 2008. His bodyheight and weight were 155 cm and 45.5 kg, respec-

Corresponding author:Kazuhisa Urushihata
First Department of Internal M edicine, Shinshu Univer-tively. There was no weight loss and perform-sity School of M edicine, 3‑1‑1 Asahi, M atsumoto‑city,

ance status was good. Physical examinations

Nagano‑prefecture 390‑8621, Japan

were unremarkable. Laboratory data including

No. 5, 2011321

Urushihata.Agatsuma.Yokoyama et al.

hematology, chemistry, and tumor markers weredose of 80 mg/m everytwo weeks with a two‑week

within normal limits, although the inﬂammatory

drug‑free interval.During S‑1 administration,appe-parameter (CRP) was positive (Table 1). Chest

tite loss (grade 1) and leukocytopenia (grade 1)

computed tomography (CT)revealed a mass in thewere sometimes observed, but neither severe

right upper lobe and the swelling of hilar

hematological nor non‑hematological toxicities,

lymphadenopathy (Fig.1A). Bronchoﬁberscopy was

requiring cessation or postponing of the agent were

performed and the cytological ﬁndings revealed

observed for about three years. In regard to themalignant cells suggesting large‑cell carcinoma ortumor responses, the tumor in the right upper lobe

poorly diﬀerentiated adenocarcinoma (Fig 2).

and hilar lymphadenopathy disappeared from theEpidermal growth factor receptor mutation was notchest CT (Fig.1B). S‑1 therapy has been continued

found in the specimens.Systemic evaluations includ-and the patient remains well with complete

ing F‑ﬂuorodeoxyglucose positron emission tomo-response status.

graphy were performed, and the clinical stage wasDiscussion

estimated as the locally advanced and inoperable
stage (III B). The present case was treated with S‑We reported our clinical experience with a

1 monotherapy after written informed consent.Thepatient of 80 years who showed a complete responseschedule of administration of S‑1 was orally at ato S‑1 monotherapy over 3 years. Clinically, weinevitably encounter diﬃculty in the treatment ofTable 1 Laboratory data on admission

advanced NSCLC in elderly patients. Whereas thepopulation of such patients had been increasing,theHematology
WBCRBC
HbHt
PlateletChemistry
Total protein
Albumin
BUN
Creatinine
AST
ALT
LDH
ALP
γ‑GTP
T.BilNaK
ClCa
GlucoseCRP
Tumor markers
CEA
CA19 ‑9SCC
322

inadequacy of a consistent approach to treatment is6680/μL
399 ×10 /μL
11.6 g/dL
36.1%
28.2×10 /μL

becoming increasingly apparent.Thus,the questionof how best to treat elderly NSCLC patients is
becoming increasingly important.
There have been some clinical studies focusing on
the eﬀectiveness of chemotherapy in the over‑

6.8 g/dL
3.0 g/dL
15 mg/dL
0.70 mg/dL
17 IU/L
11 IU/L
188 IU/L

sevententies population. Initially, the Elderly Lung
Cancer Vinorelbine Italian Study Group reported
signiﬁcantly superior survival and quality of life(QOL) with single‑agent vinorelbine over best
supportive care . Subsequently, a Japanese groupconducted a randomized phase III study evaluating

250 IU/L
12 IU/L
0.66 mg/dL
140 mEq/L
4.2 mEq/L
108 mEq/L
7.9 mg/dL

the eﬃcacy and safety of docetaxel vesus vinorel-136 mg/dL
1.10 mg/dL

therapy has been recommended for elderly patientsbine in elderly NSCLC patients .Although docetaxel monotherapy failed to show overall survival
beneﬁt in that study,it did improve progression‑freesurvival, response rate and disease‑related symptoms versus vinorelbine. Thus, single agent chemowith NSCLC. However, since the frequencies ofenrolled patients over 80 years in these studies were

1.5 ng/mL (＜3.5)
25.0 U/mL (＜37.0)
1.3 ng/mL (＜2.0)

too small (10‑15%) , the optimal agent or theindications for chemotherapy in patients over 80
remain unclear.
Shinshu Med J Vol.59

S‑1 chemotherapy in elderly NSCLC

ＡＢ

Chest computed tomography before (A) and after (B) S‑1 mono‑chemotherapy. A ; before chemotherapy,

Fig. 1swelling of right hilar lymphadenopathy and mass in right upper lung ﬁelds.B ;three years after S‑1 monotherapy. The lymphadenopathy and mass have disappeared after S‑1 mono‑chemotherapy over three years (B).

Fig. 2

Cytological ﬁndings taken from bronchoﬁberscopy revealed large‑sized tumor cells with hyperchromaticnucleoli and emperipolesis, suggesting a large‑cell carcinoma or poorly diﬀerentiated adenocarcinoma.

No. 5, 2011323

Urushihata.Agatsuma.Yokoyama et al.

In the ﬁeld of NSCLC,in a phase II trial of S‑1and thymidylate synthase. Unfortunately, his-59 advanced NSCLC patients without a previous

tological analysis is unavailable in the present study

history of chemotherapy were orally administeredbecause of the small sample.However,the complete

S‑1 at approximately 40 mg/m twice a day for 28

response to S‑1 and prolonged disease‑free survivaldays, followed by a 2‑week drug‑free period. Theover 3 years in the present case is an extremelyrare

response rate (RR)and median survival time(MST)and encouraging experience. Based on our experi-

were 22% and 10.2 months,respectively.As expect-ence, we would like to emphasize that S‑1 may be

ed, the incidence of severe gastrointestinal tox-

useful as an alternative chemotherapy agent for

icities was low, and in regard to the hematologic

elderly patients with advanced NSCLC.There havetoxicities, there were few severe events. M ajor

been no prospective studies for evaluating the clini-

adverse events with S‑1 were gastrointestinal tox-

cal usefulness of S‑1 in elderly patients withicity and myelosuppression,and both were reported

NSCLC. Further clinical experiences and studies

to be mild in a phase II study conducted in patientsare required to fully determine the therapeuticwith chemo‑naı
ve advanced NSCLC :grade 3 or 4

beneﬁt of S‑1 in unresectable NSCLC in elderly

neutropenia, 6.8% ; diarrhea, 8.5% ; stomatitis,patients.

1.7% (1/59). Thus, S‑1 was consdered to be active

In summary, based on the clinical results in sev-. Although theeral trials including our case,S‑1 monotherapymay

study was done in patients under 75 years old, S‑1

be considered as an option in the treatment ofmight be a novel therapy especially in elderly

advanced NSCLC in the elderly. This novel agent

patients with NSCLC because of the fewer tox-

merits further clinical investigation for the treat-icities.

ment of elderly patients with NSCLC.The informa-for NSCLC with fewer toxicities

It has been demonstrated that the anticancer

tion obtained from this case might provide a newactivity of S‑1 is closely related to the intratumoral

direction for clinical trials on the treatment ofexpression of dihydropyrimidine dehydrogenase

inoperable NSCLC in the elderly.

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