Faculty Profiles - HOTTA Katsuyuki

Chemoradiotherapy for locally advanced lung cancer patients with interstitial lung abnormalities. International journal

Hisao Higo, Toshio Kubo, Satoko Makimoto, Go Makimoto, Hiroki Ihara, Yoshihisa Masaoka, Takashi Ninomiya, Eiki Ichihara, Kadoaki Ohashi, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Nagio Takigawa, Yoshinobu Maeda, Katsuyuki Kiura

Japanese journal of clinical oncology 49 ( 5 ) 458 - 464 2019.5

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

INTRODUCTION: Although chemoradiotherapy for locally advanced lung cancer has the potential for cure, treatment is avoided in patients with interstitial lung disease because of the risk for severe radiation pneumonitis. Interstitial lung abnormalities (ILA) can be evaluated using high-resolution computed tomography (HRCT) to assess interstitial changes. In this study, we retrospectively examined the feasibility and efficacy of chemoradiotherapy for locally advanced lung cancer patients with ILA. METHODS: Patients who underwent chemoradiotherapy for locally advanced lung cancer at Okayama University Hospital between 2012 and 2015 were reviewed retrospectively. HRCT prior to treatment was evaluated by one pulmonologist and two radiologists using a sequential reading method. RESULTS: Of the 77 patients enrolled in this study, ILA was present in 25 (32.5%) and indeterminate ILA in 24 patients; 28 patients did not have ILA. Desaturation at rest (SpO2 < 95%) and honeycombing on HRCT were not observed in ILA patients. Only one patient with ILA had a low vital capacity (%VC < 80%). Severe radiation pneumonitis (≥Grade 2) occurred in 36.0% of the patients with ILA, but it was controllable; Grade 4 or 5 was not observed. Multivariate analysis showed that >25% of the lung volume receiving >20 Gy was risk factors of severe radiation pneumonitis, but ILA was not. The 2-year survival rates of patients with and without ILA were 56.8% and 74.1%, respectively, but the difference was not significant (P = 0.33). CONCLUSIONS: Chemoradiotherapy was feasible and effective in some patient population with ILA without desaturation, low VC and honeycombing on HRCT.

DOI： 10.1093/jjco/hyz016

Recent treatment strategy for advanced squamous cell carcinoma of the lung in Japan.

Satoru Senoo, Kiichiro Ninomiya, Katsuyuki Hotta, Katsuyuki Kiura

International journal of clinical oncology 24 ( 5 ) 461 - 467 2019.5

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

Squamous cell carcinoma of the lung is associated with smoking in its development and comprises about 20-30% of all lung cancers. Its treatment strategy had been limited for the past decades, inevitably resulting in the poor outcome. However in the 2010s, it has dramatically changed mainly with the recent clinical introduction of immune checkpoint inhibitors. In this review, we will introduce various clinical studies involving squamous cell carcinoma of the lung.

DOI： 10.1007/s10147-019-01424-y

Rapid and Long-term Response of Pulmonary Pleomorphic Carcinoma to Nivolumab.

Satoru Senoo, Takashi Ninomiya, Go Makimoto, Kazuya Nishii, Hirohisa Kano, Hiromi Watanabe, Yusuke Hata, Toshio Kubo, Takehiro Tanaka, Katsuyuki Hotta, Yoshinobu Maeda, Katsuyuki Kiura

Internal medicine (Tokyo, Japan) 58 ( 7 ) 985 - 989 2019.4

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

Pulmonary pleomorphic carcinoma (PPC) is a rare very aggressive subtype of non-small cell lung cancer. We herein report a case of PPC that showed a rapid response to nivolumab. The patient, whose multiple tumors had progressed very aggressively, was treated with nivolumab, an anti-programmed cell death-1 (PD-1) antibody. The tumors dramatically shrank after one cycle of nivolumab. The tumors were positive for programmed cell death ligand 1 (PD-L1). An immunohistochemical analysis revealed numerous PD-1+, CD68+ and CD206+ macrophages. This PD-1 antibody may be a good treatment option, especially in tumors that express PD-L1 and which show PD-1+ macrophage infiltration.

DOI： 10.2169/internalmedicine.0890-18

Phase 2 Study of Afatinib Alone or Combined With Bevacizumab in Chemonaive Patients With Advanced Non-Small-Cell Lung Cancer Harboring EGFR Mutations: AfaBev-CS Study Protocol. International journal

Takashi Ninomiya, Nobuhisa Ishikawa, Koji Inoue, Toshio Kubo, Masayuki Yasugi, Takuo Shibayama, Tadashi Maeda, Kazunori Fujitaka, Masahiro Kodani, Toshihide Yokoyama, Shoichi Kuyama, Nobuaki Ochi, Yutaka Ueda, Seigo Miyoshi, Toshiyuki Kozuki, Yoshihiro Amano, Tetsuya Kubota, Keisuke Sugimoto, Akihiro Bessho, Tomoya Ishii, Kazuhiko Watanabe, Isao Oze, Katsuyuki Hotta, Katsuyuki Kiura

Clinical lung cancer 20 ( 2 ) 134 - 138 2019.3

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

Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has demonstrated a significant survival benefit over platinum-based chemotherapy in a first-line setting in advanced non-small-cell lung cancer (NSCLC) harboring EGFR exon 19 deletion. In addition, we and other groups have shown there to be favorable progression-free survival (PFS) outcomes, with acceptable toxicity profiles, with bevacizumab and first-generation EGFR-TKI combination therapy. On the basis of the above, we hypothesized that a combination of bevacizumab and afatinib could potentially improve efficacy. In our phase 1 study, a daily 30 mg dose of afatinib and 15 mg/kg intravenous bevacizumab every 3 weeks was well tolerated and was defined as the recommended dose. We have initiated a randomized phase 2 trial comparing afatinib (30 mg daily) and bevacizumab (15 mg/kg every 3 weeks) with afatinib (40 mg daily) alone for nonsquamous NSCLC harboring EGFR common mutations as a first-line therapy. A total of 100 patients will be enrolled onto this study and randomized in a 1:1 ratio. Patients will continue to receive treatment until disease progression or unacceptable toxicity. The primary end point is PFS, and the secondary end points are overall survival, tumor response, and time to treatment failure. The power is greater than 50% under the assumptions of a median PFS of 12 months for the afatinib group and a hazard ratio of 0.6 for the combination group (2-sided α = 0.05). We hypothesize that the combination therapy will be more efficacious than standard therapies for EGFR-mutant NSCLC patients.

DOI： 10.1016/j.cllc.2018.10.008

Significance of re-biopsy of histological tumor samples in advanced non-small-cell lung cancer in clinical practice.

Katsuyuki Hotta, Kiichiro Ninomiya, Eiki Ichihara, Katsuyuki Kiura

International journal of clinical oncology 24 ( 1 ) 41 - 45 2019.1

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

The significance of evaluating oncogenes, including EGFR mutations, ALK abnormalities, and PD-L1 expression has become broadly recognized with recent advances in molecular biology. It is now extremely important to investigate tumor oncogene status in each patient at the initial diagnosis. By contrast, the significance of conducting a re-biopsy in the salvage setting has not been systematically reviewed. This review reports that the significance of a re-biopsy varies depending on the clinical situation.

DOI： 10.1007/s10147-018-1344-x

A Phase II Trial of First-Line Combination Chemotherapy With Cisplatin, Pemetrexed, and Nivolumab for Unresectable Malignant Pleural Mesothelioma: A Study Protocol. International journal

Nobukazu Fujimoto, Keisuke Aoe, Toshiyuki Kozuki, Isao Oze, Katsuya Kato, Takumi Kishimoto, Katsuyuki Hotta

Clinical lung cancer 19 ( 5 ) e705-e707 2018.9

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

BACKGROUND: The purpose of this study is to assess the efficacy and safety of combination chemotherapy with cisplatin, pemetrexed, and nivolumab for unresectable malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Patients with untreated, advanced, or metastatic MPM who meet the inclusion and exclusion criteria will be included. A total of 18 patients will be enrolled from 4 Japanese institutions within 1 year. Combination chemotherapy with cisplatin (75 mg/m2), pemetrexed (500 mg/m2), and nivolumab (360 mg/person) is administered every 3 weeks for a total of 4 to 6 cycles. Then, maintenance therapy with nivolumab will be administered until disease progression, unacceptable toxicities, or the patient's condition meets the withdrawal criteria. The primary end point is the centrally reviewed overall response rate. The secondary end points include the disease control rate, overall survival, progression-free survival, and adverse events. CONCLUSION: This phase II trial evaluating first-line combination chemotherapy for unresectable MPM commenced in January 2018. This is the first prospective trial to evaluate the effect of an anti-programmed death-1 antibody combined with cisplatin and pemetrexed for unresectable MPM.

DOI： 10.1016/j.cllc.2018.05.001

Is Surgery after Chemoradiotherapy Feasible in Lung Cancer Patients with Superior Vena Cava Invasion? Reviewed

Hiroki Sato, Junichi Soh, Katsuyuki Hotta, Kuniaki Katsui, Susumu Kanazawa, Katsuyuki Kiura, Shinichi Toyooka

Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia 24 ( 3 ) 131 - 138 2018.6

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

PURPOSE: The purpose of this study is to explore the possibility of surgery after chemoradiotherapy (CRT) for locally advanced-non-small-cell lung cancer (LA-NSCLC) with superior vena cava (SVC) resection in terms of prognosis and early and late postoperative course. METHODS: The medical records of NSCLC patients who underwent surgery after CRT at our institution between January 2001 and March 2016 were reviewed. We evaluated the feasibility of surgery with SVC resection after CRT. RESULTS: A total of 8 LA-NSCLC patients were enrolled in this study. The SVC management included a graft replacement in two patients, pericardial patch repair in two, and direct suture closure in four. A complete resection was achieved in seven of the eight patients (87.5%). Postoperative early and late complication rate (Clavien-Dindo classification ≥ grade III) was 25%. All the complications were manageable, and no treatment-related deaths occurred in this series. Although seven out of eight patients showed good patency of reconstructed SVC, one patient exhibited the SVC occlusion during long-term follow-up period. Regarding the prognosis, the 5-year overall survival (OS) rate was 60.0%, and the 2-year recurrence-free survival (RFS) rate was 75.0%. CONCLUSION: Our results suggest that surgery with SVC resection after CRT is a feasible procedure in terms of clinical outcomes and postoperative course.

DOI： 10.5761/atcs.oa.18-00027

Quality of life of survivors of malignant pleural mesothelioma in Japan: A cross sectional study Reviewed

Yasuko Nagamatsu, Isao Oze, Keisuke Aoe, Katsuyuki Hotta, Katsuya Kato, Junko Nakagawa, Keiko Hara, Takumi Kishimoto, Nobukazu Fujimoto

BMC Cancer 18 ( 1 ) 350 2018.3

Language：English Publishing type：Research paper (scientific journal) Publisher：BioMed Central Ltd.

Background: Previous studies have indicated that people with malignant pleural mesothelioma (MPM) have a poor quality of life (QOL)
however, information about the QOL of people with MPM in Japan is anecdotal. The aims of this study were to investigate the QOL of survivors of MPM in Japan and to determine the factors that correlate with their QOL. Methods: This was a cross sectional study. The included patients were those diagnosed with MPM in Japan. We created a self-administered questionnaire consisting of 64 questions. The questionnaires were sent to hospitals and patient advocacy groups, distributed to the patients, completed, and sent back to the researchers by postal mail. QOL was assessed with the European Organization for Research and Treatment of Cancer 16 questionnaire (QLQ) and the short version of the core domains of the Comprehensive Quality of Life Outcome questionnaire (CoQoLo). Results: In total, 133 questionnaires were collected. The QLQ assessments demonstrated that the survivors of MPM most frequently complained of fatigue, pain, sleep disturbances, and dyspnea. The symptom scales were acceptable, but the functional scales were significantly poorer for the patients with poor performance statuses (PSs). The short CoQoLo assessment was very unfavorable for 'Being free from physical pain.' Being a long-term survivor and a survivor with a poor PS were significantly correlated with poor global health status. Conclusions: Survivors of MPM have impaired function, a variety of symptoms, and lower QOL. Survivors of MPM, even those in good physical condition, need broad support.

DOI： 10.1186/s12885-018-4293-x

A phase I trial of afatinib and bevacizumab in chemo-naïve patients with advanced non-small-cell lung cancer harboring EGFR mutations: Okayama Lung Cancer Study Group Trial 1404. International journal

Takashi Ninomiya, Naoyuki Nogami, Toshiyuki Kozuki, Daijiro Harada, Toshio Kubo, Kadoaki Ohashi, Shoichi Kuyama, Kenichiro Kudo, Akihiro Bessho, Nobuaki Fukamatsu, Nobukazu Fujimoto, Keisuke Aoe, Takuo Shibayama, Keisuke Sugimoto, Nagio Takigawa, Katsuyuki Hotta, Katsuyuki Kiura

Lung cancer (Amsterdam, Netherlands) 115 103 - 108 2018.1

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

OBJECTIVE: In advanced epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC), treatment with afatinib, a second-generation EGFR-tyrosine kinase inhibitor (TKI), confers a significant survival benefit over platinum-based chemotherapy. The first-generation EGFR-TKIs gefitinib and erlotinib in combination with bevacizumab have improved progression-free survival. We hypothesized that the combination of afatinib with bevacizumab would further improve efficacy, and conducted a phase I trial to test this hypothesis. MATERIALS AND METHODS: Untreated patients with advanced EGFR-mutant NSCLC were enrolled. The primary endpoint was safety. Two doses of afatinib, 40mg/day (level 0) and 30mg/day (level -1), were evaluated in combination with 15mg/kg bevacizumab every 3 weeks. Optimal dosing was determined by dose-limiting toxicity (DLT), with the concentration at which ≤4 of 12 patients experienced toxicity considered the recommended dose. RESULTS: Nineteen patients were enrolled (level 0:5, level -1:14). Three of the five patients at level 0 experienced a DLT, which indicated that this dose was unfeasible. Three patients at level -1 developed a DLT of grade 3 non-hematological toxicity, which was soon resolved. Grade 3 or worse adverse events were experienced by all five patients at dose level 0 (diarrhea in 2, skin rash in 1, hypoxia in 1, and paronychia in 1), and by three patients at level -1 (diarrhea in 2 and anorexia in 1). Among 16 evaluable patients, 1 had a complete response, 12 had partial responses, and 0 had progressive disease. CONCLUSION: Afatinib plus bevacizumab (level -1) was well tolerated and showed evidence of favorable disease control. This combination therapy may represent a potent therapeutic option for patients with EGFR-mutant NSCLC.

DOI： 10.1016/j.lungcan.2017.11.025

Discomfort during bronchoscopy performed after endobronchial intubation with fentanyl and midazolam: a prospective study. International journal

Daisuke Minami, Nagio Takigawa, Hirohisa Kano, Takashi Ninomiya, Toshio Kubo, Eiki Ichihara, Kadoaki Ohashi, Akiko Sato, Katsuyuki Hotta, Masahiro Tabata, Mitsune Tanimoto, Katsuyuki Kiura

Japanese journal of clinical oncology 47 ( 5 ) 434 - 437 2017.5

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

Objective: Although endobronchial intubation during a bronchoscopic examination is useful for invasive procedures, it is not routine practice in Japan. The present study evaluated discomfort due to endobronchial intubation using fentanyl and midazolam sedation during bronchoscopy. Methods: Thirty-nine patients were enrolled prospectively from November 2014 to September 2015 at Okayama University Hospital. Fentanyl (20 µg) was administered to the patients just before endobronchial intubation, and fentanyl (10 µg) and midazolam (1 mg) were added as needed during the procedure. A questionnaire survey was administered 2 h after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: excellent (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question ('Do you remember the bronchoscopic examination?') was also asked. Predefined parameters (blood pressure, heart rate, oxygen saturation and complications) were recorded. Results: The enrolled patients included 22 males and 17 females; their median age was 70 (range: 28-88) years. The patients received a mean dose of 47.9 µg of fentanyl (range: 30-90 µg) and 2.79 mg of midazolam (range: 1-7 mg). In total, 28 patients (71.7%) agreed to undergo a second bronchoscopic examination; the mean levels of discomfort and for the re-examination were 2.07 points each. About 41% of the patients remembered the bronchoscopic examination. No severe complications were reported. Conclusion: Endobronchial intubation using fentanyl and midazolam sedation during an invasive bronchoscopic procedure might be recommended. Clinical Trial Registration: UMIN000015578 in the UMIN Clinical Trials Registry.

DOI： 10.1093/jjco/hyx022

同時化学放射線療法後の手術により治療した局所進行性NSCLCの生存者における第二原発性癌(Second primary cancer in survivors of locally advanced NSCLC treated with concurrent chemoradiation followed by surgery)

Makimoto Go, Kubo Toshio, Oze Isao, Ohashi Kadoaki, Hotta Katsuyuki, Takigawa Nagio, Toyooka Shinichi, Katsui Kuniaki, Tanimoto Mitsune, Kiura Katsuyuki

日本呼吸器学会誌 6 ( 増刊 ) 345 - 345 2017.3

野生型EGFR遺伝子を有する高齢者未治療進行非小細胞肺癌に対するカルボプラチンとS-1併用療法の第2相試験(OLCSG1202)

西井和也, 二宮貴一朗, 久保寿夫, 久山彰一, 別所昭宏, 越智宣敬, 堀田勝幸, 瀧川奈義夫, 谷本光音, 木浦勝行

日本内科学会雑誌 106 ( Suppl. ) 257 - 257 2017.2

Randomized feasibility study of S-1 for adjuvant chemotherapy in completely resected Stage IA non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 0701 Reviewed

Junichi Soh, Norihito Okumura, Masao Nakata, Hiroshige Nakamura, Minoru Fukuda, Masafumi Kataoka, Shinsuke Kajiwara, Yoshifumi Sano, Motoi Aoe, Kazuhiko Kataoka, Katsuyuki Hotta, Keitaro Matsuo, Shinichi Toyooka, Hiroshi Date

JAPANESE JOURNAL OF CLINICAL ONCOLOGY 46 ( 8 ) 741 - 747 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

Objective: The aim of this multicenter study was to determine the appropriate administration schedule for S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely resected pathological-Stage IA ( tumor diameter, 2-3 cm) non-small-cell lung cancer.
Methods: Patients were randomly assigned to receive adjuvant chemotherapy consisting of either the 4-week oral administration of S-1 ( 80-120 mg/body/day) followed by a 2-week rest ( Group A), or the 2-week oral administration of S-1 ( 80-120mg/body/day) followed by a 1-week rest ( Group B). The duration of adjuvant chemotherapy was 1 year in both arms. The primary endpoint was compliance, namely drug discontinuation-free survival, which was calculated using the Kaplan-Meier method with log-rank test.
Results: Eighty patients were enrolled in this study, and 76 patients actually received S-1 treatment. The drug discontinuation-free survival rates at 1 year were 49.1% in Group A and 52.7% in Group B ( P = 0.373). The means of the relative dose intensities were 55.3% in Group A and 64.6% in Group B ( P = 0.237). There were no treatment-related deaths. Patients with grade 3/ 4 toxicities were significantly more frequent in Group A ( 40.5%) than in Group B ( 15.4%, P = 0.021). The 2-year relapse-free survival rates were 97.5% in Group A and 92.5% in Group B, and the 2-year overall survival rates were 100% in both groups.
Conclusions: The feasibility showed no significant difference between the two groups among patients with completely resected Stage IA ( tumor diameter, 2-3 cm) non-small-cell lung cancer.

DOI： 10.1093/jjco/hyw062

Development of a skin rash within the first week and the therapeutic effect in afatinib monotherapy for EGFR-mutant non-small cell lung cancer (NSCLC): Okayama Lung Cancer Study Group experience. International journal

Kenichiro Kudo, Katsuyuki Hotta, Akihiro Bessho, Naoyuki Nogami, Toshiyuki Kozuki, Shoichi Kuyama, Koji Inoue, Shingo Harita, Toshiaki Okada, Kenichi Gemba, Masanori Fujii, Nagio Takigawa, Naohiro Oda, Mitsune Tanimoto, Katsuyuki Kiura

Cancer chemotherapy and pharmacology 77 ( 5 ) 1005 - 9 2016.5

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

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are now key agents in treating EGFR-mutant non-small cell lung cancer (NSCLC). The efficacy of gefitinib or erlotinib monotherapy can be predicted by the development of a skin rash. However, it has not been fully evaluated if this is the case with afatinib monotherapy. METHODS: We retrospectively studied 49 consecutive patients with EGFR-mutant NSCLC who received afatinib therapy between 2009 and 2015. The relationship of several toxicities with tumor response was examined. RESULTS: Grade 2, or more severe, common adverse events (AEs) included skin rash in 17 patients (35 %), diarrhea in 19 (39 %) and mucositis in 15 (31 %). Of these, the number of patients who developed ≥Grade 2 AEs during the first week after the initiation of afatinib therapy was: five patients had skin rash (10 %), 12 patients had diarrhea (25 %) and four patients had mucositis (8 %). As for an objective response, 21 (43 %) of the 49 had a partial response. Associating the AEs with the antitumor effect, those who had a ≥Grade 2 skin rash within the first week tended to have a greater tumor response compared with those without a rash (80 vs. 39 %; p = 0.077). CONCLUSION: Our small study demonstrated that the early development of a skin rash might be associated with the response to afatinib monotherapy.

DOI： 10.1007/s00280-015-2910-9

インターロイキン-6はEGFRに変異を有する進行性のNSCLC患者におけるゲフィチニブの治療効果に関する価値のある予測マーカである(Interleukin6 is a Valuable Predictive Marker for Therapeutic Effect of Gefitinib in Patients with Advanced NSCLC Harboring EGFR mutations)

Tamura Tomoki, Hotta Katsuyuki, Kato Yuka, Gotoda Hiroko, Tanaka Takehiro, Ichimura Koichi, Kubo Toshio, Ohashi Kadoaki, Ichihara Eiki, Kiura Katsuyuki

日本呼吸器学会誌 5 ( 増刊 ) 373 - 373 2016.3

EGFR変異型の非小細胞肺がんの移植モデルに対するエルロチニブと併用した抗VEGFR-2抗体の有効性(Efficacy of an Anti-VEGFR-2 Antibody in Combination with Erlotinib on EGFR Mutant Non-Small Cell Lung Cancer Xenograft Models)

Kayatani Hiroe, Ohashi Kadoaki, Kubo Toshio, Kudo Kenichiro, Imao Takeshi, Kato Yuka, Ninomiya Takashi, Hotta Katsuyuki, Tanimoto Mitsune, Kiura Katsuyuki

日本呼吸器学会誌 5 ( 増刊 ) 364 - 364 2016.3

Gefitinib Combined With Standard Chemoradiotherapy in EGFR-Mutant Locally Advanced Non-Small-Cell Lung Cancer: The LOGIK0902/OLCSG0905 Intergroup Study Protocol. International journal

Katsuyuki Hotta, Jiichiro Sasaki, Sho Saeki, Nagio Takigawa, Kuniaki Katsui, Koichi Takayama, Naoyuki Nogami, Yoshiyuki Shioyama, Akihiro Bessho, Junji Kishimoto, Mitsune Tanimoto, Katsuyuki Kiura, Yukito Ichinose

Clinical lung cancer 17 ( 1 ) 75 - 9 2016.1

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

Herein, we describe an ongoing phase II trial in patients with locally advanced non-small-cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR). Patients with chemotherapy-naive locally advanced disease with active EGFR mutations will receive the induction treatment, specified as gefitinib monotherapy (250 mg/body) for 8 weeks. Patients whose disease has not progressed during the induction therapy will receive cisplatin and docetaxel (40 mg/m(2)) on days 1, 8, 29, and 36, and concurrent 3-dimensional conformal thoracic radiotherapy with a single daily fraction of 2 Gy, for 5 consecutive days each week to provide a total dose of 60 Gy. The primary end point is overall survival at 24 months. A target sample size of 21 evaluable patients is considered sufficient to validate an expected rate of 85%, and 60% would be the lower limit of interest, with 80% power and a 1-sided α of 5%. Secondary end points include toxicity, response rate, and overall survival. This study will clarify whether tyrosine kinase inhibitors targeted to EGFR can produce a maximal effect in selected NSCLC patients with the relevant driver mutation, even in the locally advanced setting.

DOI： 10.1016/j.cllc.2015.08.004