Faculty Profiles - HOTTA Katsuyuki

A phase II study of amrubicin and topotecan combination therapy in patients with relapsed or extensive-disease small-cell lung cancer: Okayama Lung Cancer Study Group Trial 0401. International journal

Naoyuki Nogami, Katsuyuki Hotta, Shoichi Kuyama, Katsuyuki Kiura, Nagio Takigawa, Kenichi Chikamori, Takuo Shibayama, Daizo Kishino, Shinobu Hosokawa, Akihiko Tamaoki, Shingo Harita, Masahiro Tabata, Hiroshi Ueoka, Tetsu Shinkai, Mitsune Tanimoto

Lung cancer (Amsterdam, Netherlands) 74 ( 1 ) 80 - 4 2011.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUNDS: Chemotherapy is a mainstay in the treatment of extensive-disease small-cell lung cancer (ED-SCLC), although the survival benefit remains modest. We conducted a phase II trial of amrubicin (a topoisomerase II inhibitor) and topotecan (a topoisomerase I inhibitor) in chemotherapy-naïve and relapsed SCLC patients. METHODS: Amrubicin (35 mg/m(2)) and topotecan (0.75 mg/m(2)) were administered on days 3-5 and 1-5, respectively. The objective response rate (ORR) was set as the primary endpoint, which was assessed separately in chemotherapy-naïve and relapsed cases. RESULTS: Fifty-nine patients were enrolled (chemotherapy-naïve 31, relapsed 28). The ORRs were 74% and 43% in the chemotherapy-naïve and relapsed cases, respectively. Survival data were also promising, with a median progression-free survival time and median survival time of 5.3 and 14.9 months and 4.7 and 10.2 months in the chemotherapy-naïve and relapsed cases, respectively. Even refractory-relapsed cases responded to the treatment favorably (27% ORR). The primary toxicity was myelosuppression with grades 3 or 4 neutropenia in 97% of the patients, which led to grades 3 or 4 febrile neutropenia in 41% of the patients and two toxic deaths. CONCLUSION: This phase II study showed the favorable efficacy and moderate safety profiles of a topotecan and amrubicin two-drug combination especially in relapsed patients with ED-SCLC.

DOI： 10.1016/j.lungcan.2011.01.018

[A relapse of small-cell lung cancer ten years after concomitant chemoradiotherapy followed by high-dose chemotherapy with autologous peripheral blood stem cell transfusion].

Akihiko Taniguchi, Nagio Takigawa, Katsuyuki Hotta, Tadashi Matsumura, Mitsune Tanimoto, Katsuyuki Kiura

Nihon Kokyuki Gakkai zasshi = the journal of the Japanese Respiratory Society 49 ( 9 ) 697 - 701 2011.9

Language：Japanese Publishing type：Research paper (scientific journal)

A 57-year-old man had limited-disease small cell lung cancer in the left lower lobe of the lung. He was treated with chemotherapy with concurrent accelerated hyperfractionated thoracic radiation, followed by high-dose chemotherapy with autologous peripheral blood stem cell transplantation. He had obtained a complete response for 10 years until the tumor in the left lower lobe was detected by positron emission tomography. Bronchoscopic brushing cytology revealed small cell cancer, which was considered to be local relapse by staging work-up. He achieved a partial response with chemotherapy consisting of cisplatin and irinotecan. The progression-free survival rate at 5 years in limited-disease small cell lung cancer ranges from 10% to 25%. Although it was difficult to distinguish the relapse of lung cancer from second primary lung cancer, we considered this case as relapse because the tumor had the same cytology in the same lobe as the previous primary tumor. The residual cells refractory to concomitant chemoradiotherapy followed by high-dose chemotherapy with stem cell transplantation had survived and proliferated after 10 years.

Benefits and Adverse Events Among Elderly Patients Receiving Concurrent Chemoradiotherapy for Locally Advanced Non-small Cell Lung Cancer Analysis of the Okayama Lung Cancer Study Group Trial 0007 Reviewed

進行非小細胞肺癌に対する抗癌剤治療の第III相試験におけるPFSとOSとの関連に関する検討

堀田勝幸, 木浦勝行, 藤原義朗, 瀧川奈義夫, 久本晃子, 田端雅弘, 谷本光音

日本癌治療学会誌 46 ( 2 ) 469 - 469 2011.9

Nagio Takigawa, Katsuyuki Kiura, Yoshihiko Segawa, Katsuyuki Hotta, Akihiko Tamaoki, Yoshiyuki Tokuda, Takuya Nagata, Kazuhiko Watanabe, Kenichi Gemba, Tomonori Moritaka, Naokatsu Horita, Hiromasa Takeda, Niro Okimoto, Mitsuhiro Takemoto, Keitaro Matsuo, Tetsu Shinkai, Masahiro Tabata, Hiroshi Ueoka, Susumu Kanazawa, Mitsune Tanimoto

JOURNAL OF THORACIC ONCOLOGY 6 ( 6 ) 1087 - 1091 2011.6

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Introduction: Thoracic radiotherapy (RT) with concurrent chemotherapy may be offered to selected elderly patients with locally advanced non-small cell lung cancer. The Okayama Lung Cancer Study Group (OLCSG) 0007 trial with patients up to 75 years showed that with concurrent RT, docetaxel and cisplatin (DP) chemotherapy was an alternative to mitomycin C, vindesine, and cisplatin (MVP) chemotherapy.
Methods: Of the 99 patients in the DP arm, 73 were younger than 70 years and 26 were 70 years or older. Of the 101 patients in the MVP arm, 75 were younger than 70 years and 26 were 70 years or older. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method and were compared using an early period weighted log-rank test. Toxicities and treatment intensities were compared by chi(2) and t tests, respectively.
Results: OS and PFS tended to be longer in the DP arm versus MVP arm: median OS (months), 27.5 versus 22.9 (p = 0.109) and 25.6 versus 23.4 (p = 0.064) in the >= 70-year and <70-year groups, respectively; median PFS (months), 19.0 versus 11.5 (p = 0.175) and 12.0 versus 9.3 (p = 0.132) in the >= 70-year and less than 70-year groups, respectively. Severe toxicity (neutropenia, esophagitis, and pneumonitis) rates did not differ between age groups. Nevertheless, the absence of statistically significant differences in this retrospective analysis might be due to the small number of patients. Radiation intensity was similar between the groups, but chemotherapy intensity was lower in the >= 70-year group.
Conclusion: Chemotherapy with concurrent RT may be effective and tolerable in elderly patients with locally advanced non-small cell lung cancer.

DOI： 10.1097/JTO.0b013e318213f86a

Other Link： http://orcid.org/0000-0003-1761-6314

Cure- or Care-Oriented Regimen for Stage III Non-Small-Cell Lung Cancer? Reviewed

Katsuyuki Hotta, Nagio Takigawa, Keitaro Matsuo, Katsuyuki Kiura

JOURNAL OF CLINICAL ONCOLOGY 29 ( 11 ) E320 - E320 2011.4

A phase I study of S-1 with concurrent thoracic radiotherapy in elderly patients with localized advanced non-small cell lung cancer. International journal

Nagio Takigawa, Katsuyuki Kiura, Katsuyuki Hotta, Shinobu Hosokawa, Naoyuki Nogami, Keisuke Aoe, Kenichi Gemba, Keiichi Fujiwara, Shingo Harita, Mitsuhiro Takemoto, Kengo Himei, Tetsu Shinkai, Yoshirou Fujiwara, Saburo Takata, Masahiro Tabata, Susumu Kanazawa, Mitsune Tanimoto

Lung cancer (Amsterdam, Netherlands) 71 ( 1 ) 60 - 4 2011.1

Language：English Publishing type：Research paper (scientific journal)

S-1, an oral 5-fluorouracil derivative, is effective against advanced non-small cell lung cancer (NSCLC) with mild toxicity and synergistic effects with radiation in preclinical trials. In this phase I study, we evaluated the dose-limiting toxicity and recommended dose of S-1 for a future phase II study when administered concurrently with thoracic radiation (total dose of 60 Gy at 2 Gy per daily fraction) in elderly patients (>75 years old) with localized advanced NSCLC. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day. Twenty-two previously untreated patients were enrolled in this study. Dose-limiting toxicity included febrile neutropenia, thrombocytopenia, stomatitis, and pneumonitis. One patient had grade 5 radiation pneumonitis. No other patient experienced radiation pneumonitis or esophagitis exceeding grade 2. The recommended dose for S-1 was determined to be 80 mg/m(2)/day, which produced an overall response rate of 75% (n=12). The median progression-free survival time was 11.5 months (95% confidence interval: 7.1-15.8 months) with a median follow-up time of 27.9 months. These results indicate that concurrent treatment with S-1 and thoracic radiation is a feasible option for NSCLC in the elderly. A phase II study is currently under way.

DOI： 10.1016/j.lungcan.2010.04.012

P2-1 再燃の診断に気管支鏡検査が有用であった慢性好酸球性肺炎の1例(IgG4関連肺疾患/びまん性,ポスター2,第34回日本呼吸器内視鏡学会学術集会)

能島大輔, 谷本安, 栗本悦子, 村上斗司, 二宮崇, 堀田勝幸, 瀧川奈義夫, 宮原信明, 金廣有彦, 田端雅弘, 木浦勝行, 片岡幹男, 久本晃子, 丸川将臣, 谷本光音

気管支学 33 S229 2011

Association between poor performance status and risk for toxicity during erlotinib monotherapy in Japanese patients with non-small cell lung cancer: Okayama Lung Cancer Study Group experience Reviewed International journal

Katsuyuki Hotta, Katsuyuki Kiura, Nagio Takigawa, Etsuji Suzuki, Hiroshige Yoshioka, Toshiaki Okada, Daizo Kishino, Hiroshi Ueoka, Koji Inoue, Masahiro Tabata, Mitsune Tanimoto

Lung Cancer 70 ( 3 ) 308 - 312 2010.12

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

Background: The relationship between poor performance status (PS) and toxicity during chemotherapy is controversial. We examined this for erlotinib monotherapy in non-small cell lung cancer (NSCLC) patients.
Patients and methods: Toxicity during the first month of therapy was recorded in 209 patients receiving erlotinib for NSCLC, and its association with PS was assessed.
Results: Of 209 patients, 52, 115, 30 and 12 had a PS of 0, 1, 2 and 3-4, respectively. Treatment was discontinued in 26% of patients within 1 month, with a higher rate in poorer PS patients (17%, 25%, 37% and 42%). Discontinuation was predominantly due to disease progression, rather than adverse events, in both the whole cohort (82% vs. 18%) and the poorest PS subgroup (100% vs. 0%). Three, two, and four patients with a PS of 1,2 and 3-4, respectively, died within 1 month; all six deaths of PS 2-4 patients were attributed to disease progression. Treatment interruption and dose reduction rates were similar among the subgroups. The principal adverse event was skin rash, with identical incidence in all PS subgroups.
Conclusions: Poor PS is unlikely to increase the risk for toxicity during erlotinib monotherapy, but was related to low compliance, probably because of disease progression rather than treatment-related toxicity. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.lungcan.2010.03.008

Desire for Information and Involvement in Treatment Decisions Lung Cancer Patients' Preferences and Their Physicians' Perceptions: Results from Okayama Lung Cancer Study Group Trial 0705 Reviewed

Katsuyuki Hotta, Katsuyuki Kiura, Nagio Takigawa, Hiroshige Yoshioka, Hidetoshi Hayashi, Hajime Fukuyama, Akihiro Nishiyama, Toshihide Yokoyama, Shoichi Kuyama, Shigeki Umemura, Yuka Kato, Naoyuki Nogami, Yoshihiko Segawa, Masayuki Yasugi, Masahiro Tabata, Mitsune Tanimoto

JOURNAL OF THORACIC ONCOLOGY 5 ( 10 ) 1668 - 1672 2010.10

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Introduction: This study explores patient preferences for involvement in lung cancer treatment decisions and the extent of concordance between the views of patients and physicians on decisional roles. The impact of demographic and psychosocial characteristics on the decisional role of patients is also examined.
Methods: Patients with relapsed non-small cell lung cancer who were candidates for a phase II trial of erlotinib monotherapy were recruited. Patients were interviewed after they had learned of their relapse and the treatment decision had been made but before pharmacologic intervention.
Results: Most of the 28 participants were married, had a smoking history, and were well educated. They reported moderate levels of depression and anxiety. Initially, 14% of the patients reported a preference for active decision making; later, 29% believed that the primary responsibility for the treatment decision had been theirs. Only 54% of the patients agreed with the physician's assessment of how the treatment decision was made (kappa = 0.31; test of symmetry, p = 0.23). The depression score was significantly associated with a patient's preferred level of control (p < 0.01).
Conclusions: The limited concordance between patient preference and perception and between patient and physician perceptions regarding how the treatment decision was made suggests that physicians should more accurately identify patient preferences by directly asking patients at the beginning of each clinical encounter.

DOI： 10.1097/JTO.0b013e3181f1c8cb

Phase III Trial Comparing Docetaxel and Cisplatin Combination Chemotherapy With Mitomycin, Vindesine, and Cisplatin Combination Chemotherapy With Concurrent Thoracic Radiotherapy in Locally Advanced Non-Small-Cell Lung Cancer: OLCSG 0007 Reviewed

Yoshihiko Segawa, Katsuyuki Kiura, Nagio Takigawa, Haruhito Kamei, Shingo Harita, Shunkichi Hiraki, Yoichi Watanabe, Keisuke Sugimoto, Takuo Shibayama, Toshiro Yonei, Hiroshi Ueoka, Mitsuhiro Takemoto, Susumu Kanazawa, Ichiro Takata, Naoyuki Nogami, Katsuyuki Hotta, Akio Hiraki, Masahiro Tabata, Keitaro Matsuo, Mitsune Tanimoto

JOURNAL OF CLINICAL ONCOLOGY 28 ( 20 ) 3299 - 3306 2010.7

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC CLINICAL ONCOLOGY

Purpose To demonstrate the efficacy of docetaxel and cisplatin (DP) chemotherapy with concurrent thoracic radiotherapy (TRT) for patients with locally advanced non-small-cell lung cancer (LA-NSCLC).
Patients and Methods Patients age 75 years or younger with LA-NSCLC, stratified by performance status, stage, and institution, were randomly assigned to two arms consisting of DP (docetaxel 40 mg/m(2) and cisplatin 40 mg/m(2) on days 1, 8, 29, and 36) or mitomycin, vindesine, and cisplatin (MVP) chemotherapy with concurrent TRT.
Results Between July 2000 and July 2005, 200 patients were allocated into either the DP or MVP arm. The survival time at 2 years, a primary end point, was favorable to the DP arm (P = .059 by a stratified log-rank test as a planned analysis and P = .044 by an early-period, weighted log-rank as an unplanned analysis). There was a trend toward improved response rate, 2-year survival rate, median progression-free time, and median survival in the DP arm (78.8%, 60.3%, 13.4 months, and 26.8 months, respectively) compared with the MVP arm (70.3%, 48.1%, 10.5 months, and 23.7 months, respectively), which was not statistically significant (P > .05). Grade 3 febrile neutropenia occurred more often in the MVP arm than in the DP arm (39% v 22%, respectively; P = .012), and grade 3 to 4 radiation esophagitis was likely to be more common in the DP arm than in the MVP arm (14% v 6%, P = .056).
Conclusion DP chemotherapy combined with concurrent TRT is an alternative to MVP chemotherapy for patients with LA-NSCLC.

DOI： 10.1200/JCO.2009.24.7577

Other Link： http://orcid.org/0000-0003-1761-6314

A Phase II Trial of Erlotinib Monotherapy in Pretreated Patients with Advanced Non-small Cell Lung Cancer Who Do Not Possess Active EGFR Mutations Okayama Lung Cancer Study Group Trial 0705 Reviewed

Hiroshige Yoshioka, Katsuyuki Hotta, Katsuyuki Kiura, Nagio Takigawa, Hidetoshi Hayashi, Shingo Harita, Shoichi Kuyama, Yoshihiko Segawa, Haruhito Kamei, Shigeki Umemura, Akihiro Bessho, Masahiro Tabata, Mitsune Tanimoto

JOURNAL OF THORACIC ONCOLOGY 5 ( 1 ) 99 - 104 2010.1

Language：English Publishing type：Research paper (scientific journal) Publisher：LIPPINCOTT WILLIAMS & WILKINS

Backgrounds: Efficacy of gefitinib therapy strongly depends on epidermal growth factor receptor (EGFR)-mutation status in Asian patients with non-small cell lung cancer. Recently, the survival advantage of erlotinib, another tyrosine kinase inhibitor, was not affected by EGFR mutation status in a phase III trial, indicating that patients with EGFR-wild-type (EGFR-wt) tumors might also benefit from this tyrosine kinase inhibitor. The aim of this trial was to evaluate the efficacy and toxicity of erlotinib in Japanese patients with EGFR-wt tumors.
Methods: The primary end point was an objective response. Patients with EGFR-wt tumors previously receiving one to three chemotherapy regimens were enrolled in this trial. The mutation status was assessed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. Erlotinib was administered (150 mg/d) until disease progression or unacceptable toxicities occurred.
Results: Thirty patients were enrolled between January and December 2008. Objective response was observed in one patient (3.3%), and the disease became stable in 18 patients (60.0%). Skin rash was the most common side effect. Grades 3-4 adverse events included pulmonary embolism, keratitis, and anemia. Two other patients developed interstitial lung disease (grades 1 and 2). Nevertheless, all these events were reversible, resulting in no treatment-related deaths. With a median follow-Lip time of 10.7 months, the median survival time and median progression-free survival times were 9.2 and 2.1 months, respectively.
Conclusion: This is the first prospective biomarker study showing that erlotinib therapy for pretreated patients with EGFR-wt tumors seems to have a modest activity with no irreversible toxicity.

P8-8 血性の気管支肺胞洗浄液所見のために診断が遅れた肺胞蛋白症の1例(感染・びまん性肺疾患,ポスター8,第33回日本呼吸器内視鏡学会学術集会)

谷口暁彦, 谷本安, 能島大輔, 小崎佐恵子, 南大輔, 田中寿明, 高田三郎, 堀田勝幸, 宮原信明, 瀧川奈義夫, 金廣有彦, 田端雅弘, 木浦勝行, 片岡幹男, 谷本光音

気管支学 32 S200 2010

Comprehensive analysis of EGFR signaling pathways in Japanese patients with non-small cell lung cancer. Reviewed International journal

Shinobu Hosokawa, Shinichi Toyooka, Yoshiro Fujiwara, Masaki Tokumo, Junichi Soh, Nagio Takigawa, Katsuyuki Hotta, Tadashi Yoshino, Hiroshi Date, Mitsune Tanimoto, Katsuyuki Kiura

Lung cancer (Amsterdam, Netherlands) 66 ( 1 ) 107 - 13 2009.10

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

PURPOSE: Translational approach is essentially needed to return the achievement of basic researches to oncological practice. The molecular associations among EGFR mutation and the components of EGFR signaling pathways have been extensively studied in laboratory experiments, although were still controversial. Moreover, the impact of downstream signaling of EGFR on clinical features in patients with non-small cell lung cancer (NSCLC) remains undetermined. PATIENTS AND METHODS: A total of 93 surgically resected NSCLC patients were recruited the study. EGFR mutation status was analyzed by direct sequence method. The protein expression levels of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Akt (pAkt), and phosphorylated MAPK (pMAPK) were determined by immunohistochemistry. RESULTS: There were 37 (40%) patients whose tumor harboring EGFR mutations (1 in exon 18, 22 in exon 19, and 14 in exon 21). Protein expression of EGFR, pEGFR, pAkt, and pMAPK was detected in 61 (66%), 27 (29%), 58 (62%), and 41 (44%) patients, respectively. The expression of pAkt was significantly associated with female gender and never-smoking history, and it was frequently upregulated in tumors harboring EGFR mutations (p<0.05, each). Phosphorylation of EGFR was closely correlated with the EGFR protein expression (p<0.05), but not with the EGFR mutations. In regard to patient survival, none of the molecular biomarkers was predictive for survival after surgical resection, but pMAPK expression was predictive for poor prognosis after gefitinib treatment in patients with postoperative recurrence (p<0.05), suggesting the strong linkage between pMAPK expression and survival benefit from gefitinib. CONCLUSION: Our result could provide new insight into MAP kinase signaling when we treat NSCLC patients with gefitinib.

DOI： 10.1016/j.lungcan.2009.01.005

EGFR mutation, but not sex and smoking, is independently associated with favorable prognosis of gefitinib-treated patients with lung adenocarcinoma Reviewed

Shinichi Toyooka, Toshimi Takano, Takayuki Kosaka, Katsuyuki Hotta, Keitaro Matsuo, Shuji Ichihara, Yoshiro Fujiwara, Junichi Soh, Hiroki Otani, Katsuyuki Kiura, Keisuke Aoe, Yasushi Yatabe, Yuichiro Ohe, Tetsuya Mitsudomi, Hiroshi Date

Japanese Journal of Lung Cancer 49 ( 4 ) 409 - 415 2009.8

Language：Japanese

Objective. Intensive research has been conducted to identify factors associated with favorable clinical outcomes of gefitinib-treated patients with non-small-cell lung cancer. Epidermal growth factor receptor (EGFR) mutations have been reported as a predictive factor for favorable prognosis of gefitinib-treated patients with lung adenocarcinoma. However, its confounding with sex and smoking makes EGFR mutations' unique effect on patient survival. In this study, we analyzed a large-scale database to determine the survival impact of EGFR mutation against those of sex and smoking after gefitinib therapy. Materials and Methods. EGFR mutations in exon19 and exon21 defined as drug-sensitive EGFR mutations were examined to investigate the impact of EGFR mutation, sex, and smoking status on survival of 362 gefitinib-treated patients with lung adenocarcinoma. Results. Drug-sensitive EGFR mutations were detected in 169 patients (46.7%). The multivariate analysis including EGFR, sex and smoking status showed that drug-sensitive EGFR mutations were significantly related to prolonged overall survival (OS) (Hazard ratio = 0.48, 95% confidence interval = 0.36-0.63, P &lt
0.001) (PFS: Hazard ratio, 0.29, 95% confidence interval = 0.22-0.37, P &lt
0.001) and progression-free survival (PFS) (P &lt
0.001). In addition, we investigated 1) the impact of sex and smoking status according to EGFR status and 2) the impact of EGFR status according to sex and smoking status on survival. Sex and smoking status were not significantly associated with prolonged OS and PFS according to EGFR status. Drug-sensitive EGFR mutations were significantly associated with prolonged OS and PFS according to sex or smoking status. Conclusion. Our results indicated that drug-sensitive EGFR mutations were the only factor for prolonged survival of patients treated with gefitinib, suggesting that patient selection based on EGFR status for gefitinib therapy will lead to better understanding the effect of gefitinib as well as a better outcome for patients with lung adenocarcinoma. © 2009 The Japan Lung Cancer Society.

DOI： 10.2482/haigan.49.409

Scopus

Other Link： http://orcid.org/0000-0003-1761-6314

A phase I study of combination S-1 plus cisplatin chemotherapy with concurrent thoracic radiation for locally advanced non-small cell lung cancer. International journal

Kenichi Chikamori, Daizo Kishino, Nagio Takigawa, Katsuyuki Hotta, Naoyuki Nogami, Haruhito Kamei, Shoichi Kuyama, Kenichi Gemba, Mitsuhiro Takemoto, Susumu Kanazawa, Hiroshi Ueoka, Yoshihiko Segawa, Saburo Takata, Masahiro Tabata, Katsuyuki Kiura, Mitsune Tanimoto

Lung cancer (Amsterdam, Netherlands) 65 ( 1 ) 74 - 9 2009.7

Language：English Publishing type：Research paper (scientific journal)

A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.

DOI： 10.1016/j.lungcan.2008.10.019

慢性閉塞性肺疾患(COPD)を合併した進行肺非小細胞癌(NSCLC)の予後

原田大二郎, 瀧川奈義夫, 木浦勝行, 谷本安, 堀田勝幸, 平木章夫, 宮原信明, 田端雅弘, 金廣有彦, 谷本光音

日本呼吸器学会雑誌 47 ( 増刊 ) 300 - 300 2009.5

Sex difference in the influence of smoking status on the responsiveness to gefitinib monotherapy in adenocarcinoma of the lung: Okayama Lung Cancer Study Group experience Reviewed

Katsuyuki Hotta, Katsuyuki Kiura, Nagio Takigawa, Shoichi Kuyama, Yoshihiko Segawa, Toshiro Yonei, Kenichi Gemba, Keisuke Aoe, Takuo Shibayama, Keisuke Matsuo, Haruhito Kamei, Yoshiro Fujiwara, Akihiko Bessho, Tomonori Moritaka, Keisuke Sugimoto, Masahiro Tabata, Hiroshi Ueoka, Mitsune Tanimoto

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY 135 ( 1 ) 117 - 123 2009.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER

Background Gefitinib is effective in patients with lung adenocarcinoma. Smoking status also affects the responsiveness to gefitinib, but it has not been fully evaluated whether a sex difference exists in the influence of smoking on the efficacy of gefitinib in patients with lung adenocarcinoma.
Methods We reviewed the clinical records of 260 Japanese patients with lung adenocarcinoma who received gefitinib therapy ( 250 mg/day), and whose smoking status was known. Tumour response and survival were evaluated and stratified by smoking status and gender.
Results Among the 260 patients, 157 were male (60%). Median pack-years was 40 ( range 8 - 160) and 23 ( range 1 74) in male and female smokers, respectively. Objective response was observed in 62 (23.8%) of the 260 patients, and 1-year overall survival and progression-free survival were 45.1 and 24.3%, respectively. Multivariate analysis revealed that smoking status (pack-years) was an independent predictive factor for response to gefitinib [ odds ratio ( OR) = 0.971, 95% confidence interval (CI) = 0.947 - 0.995; P = 0.0159] in male patients, but not in female patients ( OR = 0.999, 95% CI = 0.957 - 1.042). Additionally, pack-years significantly influenced the overall survival in males ( hazard ratio = 1.010; 95% CI = 1.002 - 1018, P = 0.0169), while differential survival of females was not significantly predicted by this factor ( P = 0.7639).
Conclusions In male patients with lung adenocarcinoma, cumulative smoking significantly affected response and survival following gefitinib treatment, while in female patients, responsiveness to gefitinib was independent of smoking status. These results suggest that the influence of smoking habit on responsiveness to gefitinib is gender specific.

DOI： 10.1007/s00432-008-0431-1