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IRUCAA@TDC : Complete response achieved with TS-1 in tongue squamous cell carcinoma ; Report of a case

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Posted at the Institutional Resources for Unique Collection and Academic Archives at Tokyo Dental College,

Author(s)

Kosuke, Takahashi; Takashi, Eda; Mai, Tajima;

Yusuke, Suzuki; Shun, Watanabe; Ko, Ito; Naomi,

Ogura; Kazutoshi, Kamei; Toshirou, Kondoh

Journal

日本口腔検査学会雑誌, 13(1): 61-64

URL

http://doi.org/10.15041/jsedp.13.61

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Description

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Complete response achieved with TS-1

in tongue squamous cell carcinoma; Report of a case

Kosuke Takahashi

1)*

, Takashi Eda

2)

, Mai Tajima

1)

,

Yusuke Suzuki

1)

, Shun Watanabe

1)

, Ko Ito

3)

,

Naomi Ogura

4)

, Kazutoshi Kamei

1)

, Toshirou Kondoh

5)

1)Department of Dentistry and Oral Surgery, Yokohama Rosai Hospital 2)Department of Oral and Maxillofacial Radiology and Diagnosis,

Tsurumi University School of Dental Medicine

3)Department of Oral and Maxillofacial Surgery, Saitama Medical University 4)Department of Maxillofacial Surgery, Nihon University School of Dentistry at Matsudo 5)Department of Education for Dental Medicine, Tsurumi University School of Dental Medicine

Abstract

A 74-year-old woman was referred to our hospital for treatment of discomfort on the left side of her tongue. On examination, a 15×8 mm cauliflower like tumor was observed on the left side of the tongue. Cytological examination showed a Papanicolaouʼs Class Ⅴ tu-mor. The clinical diagnosis was squamous cell carcinoma. Radiographic examination in-dicated no cervical lymph node metastasis. We performed preoperative chemotherapy with TS-1 prior to conservative surgical excision. After one course of treatment, the tongue lesion had markedly reduced. She received a total of three courses of TS-1 fol-lowed by surgery, which resulted in a complete response. At follow-up evaluation 5 years after the chemotherapy, there was no evidence of recurrence.

Key words:TS-1, Complete response, oral cancer, SCC Received: November 2nd 2020 Accepted: December 1st 2020

Introduction

 Early stage squamous cell carcinoma (SCC) of the tongue has a good survival rate and ex-cellent outcomes1). The primary treatment for tongue cancer that is still in the early stages is surgical resection. TS-1 that contain Tegafur, Gimeracil, Oteracil Potassium is a useful antican-cer agent approved for use in Japan since 2001. Here, we report a case in which administration of TS-1 as the single agent for preoperative che-motherapy resulted in complete response of tongue cancer eliminating the need for surgery.

Case report

 A 74-year-old woman was referred to our hos-pital for discomfort on the left side of her tongue. Examination revealed a 15

×

8 mm cau-liflower like tumor on the left side of her tongue, with induration around the tumor, but with no associated pain, swelling or paresthesia (Fig. 1). Her medical and family histories were only posi-tive for hypertension. Cervical examination re-vealed no abnormal findings related to the sub-mandibular and upper internal cervical lymph nodes. Contrast enhanced CT imaging and Case report

 

*:3211 Kozukue-cho, Kouhoku-ku, Yokohama 222︲0036, JAPAN TEL:+81︲45︲474︲8111 FAX:+81︲45︲474︲8323

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chest radiography showed no abnormal findings indicative of metastasis (Fig. 2). Blood tests were normal at the first visit. Cytological exam-ination revealed the presence of a keratinized pearl-like structure with a large number of atypical squamous epithelial cells, suggestive of Class Ⅴ SCC (Fig. 3). A provisional diagnosis of SCC (T1N0M0) was made and incisional bi-opsy was scheduled. In the interim period till biopsy, we commenced administration of TS-1 100 mg/day as preoperative chemotherapy. This resulted in obvious decrease in the size of the tumor to 10 mm 17 days after the oral ad-ministration. Cytological examination at this time indicated that the tumor had downgraded to Papanicolaouʼs Class Ⅲ. Although we had ini-tially planned to biopsy the tumor, we decide to continue the chemotherapy and the second TS-1 course was continued under strict follow up. The tumor subsequently decreased in size and completely disappeared by 57 days (third

course) after administration of TS-1, at which time cytological examination indicated Papanico-laouʼs Class Ⅰ cells (Fig. 4). Blood tests per-formed every week during administration of TS-1 indicated that there were no serious side effects of therapy. A total of three courses of TS-1 were administered. There was clinically no recurrence at the 5-year follow-up evaluation, and cytological examination (Fig. 5) and contact macroscopy examination were negative.

Discussion

 Recent studies have reported 5-year disease-free survival and overall survival rates of 75% and 89%, respectively, in patients with early stage SCC of the tongue1︲4). Head and neck pri-mary SCC reportedly have a high sensitivity to

Fig. 1  At the first visit, a 15×8 mm cauliflower-like tumor with surrounding induration was observed on the left side of the tongue.

Fig. 2  Contrast enhanced CT image. The arrow indicates a soft tissue mass lesion with uneven contrast effect on the left side of the tongue.

Fig. 3  Cytology examination showed a keratinized pearl-like structure with a large number of atypical squamous epithelial cells, based on which the tumor was classified as Class Ⅴ disease.

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multiple drug chemotherapy, such as CDDP, with a 70︲90% response rate5, 6).

 TS-1 is an oral anticancer drug that combines two types of modulators, otastat potassium and tegafur7). It inhibits the activity of dihydropy-rimidine dehydrogenase (DPD), which is the degrading enzyme of 5-fluorouracil (5-FU), and contains otastat potassium, which reduces the gastrointestinal toxicity of 5-FU. According to the results of a preclinical phase Ⅱ trial of TS-1, the response rate for primary head and neck cancers is 48.1%, and a very high effect is re-ported using TS-1 as a single agent8). However, as with conventional anticancer agents, marrow suppression, which is one of the adverse effects of 5-FU, with TS-1 therapy has not been allevi-ated. Hence, we performed weekly blood tests from the first course of chemotherapy in our pa-tient. Our patient showed leukopenia during

the TS-1 administration period, although there were no severe adverse events, such as marrow suppression or gastrointestinal toxicity.

 Surgical resection is one of the best treatment modalities in cases of stage 1 SCC of the tongue9). However, surgical resection is accompanied by considerable functional impairment. On the oth-er hand, radiation thoth-erapy and anticancoth-er drug treatment are alternative therapeutic options for oral cancer9). Both treatments also carry the risk of xerostomia and radiation osteoarthri-tis10). In this case, the outcomes in terms of pa-tient satisfaction and quality of life were ex-tremely high. Our experience suggests that TS-1 is a good choice as single-agent cancer treatment that can potentially lead to a com-plete response. Depending on the case, TS-1 could be a new option for the treatment of ma-lignant tumors by oral drug therapy alone. It might suggest that to choose the TS-1 is useful treatment when surgical treatment is difficult especially in elderly people or patients with poor general condition. Further study is needed to confirm our observation.

Acknowledgments

 We would like to thank Dr. Suemitsu for his invaluable as-sistance with the pathological diagnosis of this case.

Reference

1) Hiroyuki S, Toshirou K, Yoshito T, Yuya Y, Toshio N, Makiko T, Ko I : Development of Contact Mucoscopy for Oral Mucosal Diseases: A Preliminary Report, J Jpn Oral Muco Member, 13:8︲15, 2007

Fig. 5  There were sporadic clumps of superficial lineage showing nuclear thickening against a mild inflammatory background, and atypical squamous epithelium showing nuclear enlargement. The tissue was classified cytologically as Papanicolaouʼs Class Ⅰ.

Fig. 4  After 57 days of administration of TS-1, the tumor had disappeared and there was no residual induration. The dotted line indicates where the tumor disappeared.

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2) Ian G, Snehal P, Jatin S: Early stage squamous cell can-cer of the oral tongue-clinicopathologic features affect-ing outcome, Cancer, 118:101︲111, 2012

3) Shim S, Cha J, Koom WS : Clinical outcomes for T1-2N0-1 oral tongue cancer patients underwent surgery with and without postoperative radiotherapy, Radiat Oncol, 43:5, 2010 doi: 10. 1186/1748-717X-5-43

4) Yuen AP, Ho CM, Chow TL, Tang LC, Cheung WY, Ng RW, Wei WI, Kong CK, Book KS, Yuen WC, Lam AK, Yuen NW, Trendell-Smith NJ, Chan YW, Wong BY, Li GK, Ho AC, Ho WK, Wong SY, Yao TJ : Prospective randomized study of selective neck dissection versus observation for N0 neck of early tongue carcinoma, Head Neck, 31:765︲772, 2009

5) Cullen KJ, Newkirk K: Future directions in chemother-apy for head and neck cancer, Head and neck cancer multidisciplinary approach, 1015︲1027, Lippincott-Ra-ven, Philadelphia, 1999

6) Homma A, Suzuki F, Oridate N, Furuta Y, Inuyama Y,

Fukuda S: Long-term complete response to treatment with TS-a in a patient with oropharyngeal squamous cell carcinoma, Gan To Kagaku Ryoho, 29:1475︲1478, 2002

7) Shirasaka T, Taguchi T : Timeline from Discovery of 5-FU to Development of an Oral Anticancer Agent S-1 and lts Drug Concept, Jpm J cancer chemother, 33: 4︲18, 2006

8) Inuyama Y, Kida A, Tsukada M, Kohno N, Satake B: Early phase 2 study of s-a in patients with advanced head and neck cancer, Jpn j cancer chemother, 25: 1151︲1158, 1998

9) Ikeda H, Takebe Y, Irie A, Mizoguchi Y, Yamada K, Shibahara K, Iguchi T: A case report of tongue squa-mous cell carcinoma showing a complete response to TS-1, Jpn J Chemother, 30:677︲679, 2003

10) Okada Y, Ohsaka F, Asanami S : Mandibular osteora-dionecrosis induced by radiation therapy of intraoral cancer, Jpn J Oral Maxillofac Surg, 30:679︲685, 1984

Fig. 1  At the first visit, a 15 × 8 mm cauliflower-like  tumor with surrounding induration was observed  on the left side of the tongue.
Fig. 4  After 57 days of administration of TS-1, the tumor  had  disappeared  and  there  was  no  residual  induration

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