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3. Dose Escalation Study of Concurrent Chemoradiotherapy With the Use of Involved-field Conformal Radiotherapy and Accelerated Hyperfractionation in Combination With Cisplatin and Vinorelbine Chemotherapy for Stage III Non–small Cell Lung Cancer: The Final Report

Author

Yoshimura, Naruo, Tada, Takuhito, Matsumoto, Yoshiya, Sawa, Kenji, Yoshimoto, Naoki, Suzumura, Tomohiro, Tanaka, Hidenori, Mitsuoka, Shigeki, Kimura, Tatsuo, Tamiya, Tomohiro, Hirashima, Tomonori, Kawaguchi, Tomoya, Kudoh, Shinzoh, Hosono, Masako, and Hirata, Kazuto

Published
2018
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6. Randomized phase II study of first-line carboplatin-paclitaxel with or without bevacizumab in Japanese patients with advanced non-squamous non-small-cell lung cancer

Author

Niho, Seiji, Kunitoh, Hideo, Nokihara, Hiroshi, Horai, Takeshi, Ichinose, Yukito, Hida, Toyoaki, Yamamoto, Nobuyuki, Kawahara, Masaaki, Shinkai, Tetsu, Nakagawa, Kazuhiko, Matsui, Kaoru, Negoro, Shunichi, Yokoyama, Akira, Kudoh, Shinzoh, Kiura, Katsuyuki, Mori, Kiyoshi, Okamoto, Hiroaki, Sakai, Hiroshi, Takeda, Koji, Yokota, Soichiro, Saijo, Nagahiro, and Fukuoka, Masahiro

Published
2012
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8. Hepatocyte Growth Factor Expression in EGFR Mutant Lung Cancer with Intrinsic and Acquired Resistance to Tyrosine Kinase Inhibitors in a Japanese Cohort

Author

Yano, Seiji, Yamada, Tadaaki, Takeuchi, Shinji, Tachibana, Keisei, Minami, Yuko, Yatabe, Yasushi, Mitsudomi, Tetsuya, Tanaka, Hidenori, Kimura, Tatsuo, Kudoh, Shinzoh, Nokihara, Hiroshi, Ohe, Yuichiro, Yokota, Jun, Uramoto, Hidetaka, Yasumoto, Kosei, Kiura, Katsuyuki, Higashiyama, Masahiko, Oda, Makoto, Saito, Haruhiro, Yoshida, Junji, Kondoh, Kazuya, and Noguchi, Masayuki

Published
2011
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10. Phase II Trial of Amrubicin for Second-Line Treatment of Advanced Non-small Cell Lung Cancer: Results of the West Japan Thoracic Oncology Group Trial (WJTOG0401)

Author

Kaneda, Hiroyasu, Okamoto, Isamu, Hayashi, Hidetoshi, Yoshioka, Hiroshige, Miyazaki, Masaki, Kudoh, Shinzoh, Kimura, Tatsuo, Sugiura, Takamune, Sawa, Toshiyuki, Takeda, Koji, Iwamoto, Yasuo, Satouchi, Miyako, Akita, Kenji, Saito, Hiroshi, Goto, Isao, Shibata, Kazuhiko, Fukuoka, Masahiro, and Nakagawa, Kazuhiko

Published
2010
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11. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial

Author

Mitsudomi, Tetsuya, Morita, Satoshi, Yatabe, Yasushi, Negoro, Shunichi, Okamoto, Isamu, Tsurutani, Junji, Seto, Takashi, Satouchi, Miyako, Tada, Hirohito, Hirashima, Tomonori, Asami, Kazuhiro, Katakami, Nobuyuki, Takada, Minoru, Yoshioka, Hiroshige, Shibata, Kazuhiko, Kudoh, Shinzoh, Shimizu, Eiji, Saito, Hiroshi, Toyooka, Shinichi, Nakagawa, Kazuhiko, and Fukuoka, Masahiro

Published
2010
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13. Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer.

Author

Fukuoka, Masahiro, Yano, Seiji, Giaccone, Giuseppe, Tamura, Tomohide, Nakagawa, Kazuhiko, Douillard, Jean-Yves, Nishiwaki, Yutaka, Vansteenkiste, Johan, Kudoh, Shinzoh, Rischin, Danny, Eek, Richard, Horai, Takeshi, Noda, Kazumasa, Takata, Ichiro, Smit, Egbert, Averbuch, Steven, Macleod, Angela, Feyereislova, Andrea, Dong, Rui-Ping, and Baselga, José

Published
2023
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26. Phase I and pharmacologic study of oral (E)-2 -deoxy-2 -(fluoromethylene) cytidine: on a daily x 5-day schedule

Author

Masuda, Noriyuki, Negoro, Shunichi, Takeda, Kouji, Takifuji, Nobuhide, Hirashima, Tomonori, Yana, Takashi, Kurata, Noriaki, Kuwabara, Takashi, Kobayashi, Satoshi, Kudoh, Shinzoh, Matsui, Kaoru, Takada, Minoru, and Fukuoka, Masahiro

Subjects
Fluorometholone -- Research, Pyrimidine nucleotides -- Dosage and administration, Pyrimidine nucleotides -- Research, Cancer -- Drug therapy, Pharmaceuticals and cosmetics industries
Abstract

Byline: Noriyuki Masuda (1), Shunichi Negoro (2), Kouji Takeda (2), Nobuhide Takifuji (2), Tomonori Hirashima (2), Takashi Yana (1), Noriaki Kurata (3), Takashi Kuwabara (3), Satoshi Kobayashi (3), Shinzoh Kudoh (1), Kaoru Matsui (1), Minoru Takada (1), Masahiro Fukuoka (4) Keywords: phase I trial; ribonucleoside diphosphate reductase inhibitor; deoxytidine analog; FMdC Abstract: (E)-2 -deoxy-2 -(fluoromethylene)cytidine (FMdC), one of the most potent inhibitors of ribonucleoside diphosphate reductase, was selected for clinical development because of its novel mechanisms of action, and strong antitumor activity against experimental tumor models. This study was designed to determine the toxicities, maximum-tolerated dose (MTD), and pharmacokinetic profile of FMdC. FMdC was given orally for 5 consecutive days every 3 or 4 weeks in patients with advanced solid tumors. The starting dose was 8 mg/m2/day. Pharmacokinetic studies were carried out on days 1 through 5 of the first cycle. Ten patients with non-small cell lung cancer received 15 courses of FMdC at doses which were de-escalated from 8 mg/m2/day to 2 mg/m2/day because of unexpected severe toxicities at the starting dose level. Neutropenia was the dose-limiting toxicity. Thrombocytopenia and anemia were mild. Flu-like symptoms and fever were the common non-hematologic toxicities. The MTD was 4 mg/m2/day, since four of six patients developed grade 3--4 neutropenia. At the 4 mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), plasma clearance, and mean residence time on day 1 were 3.20 h, 15.8 ng/ml, 2.91 l/h/kg, and 4.03 h, respectively. The recommended dose for phase II studies with this schedule is also 4 mg/m2/day for 5 days. Further investigations are necessary to establish optimal dosing schedules and routes for the administration of FMdC. Author Affiliation: (1) Department of Internal Medicine, Osaka Prefectural Habikino Hospital, Habikino, Osaka, Japan (2) Department of Respiratory Disease, Osaka City General Hospital, Miyakojima, Osaka, Japan (3) Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan (4) Department of Internal Medicine, Kinki, University School of Medicine, Osaka, Japan Article History: Registration Date: 29/09/2004

Published
1998

27. Phase II Study of Etoposide and Cisplatin With Concurrent Twice-Daily Thoracic Radiotherapy Followed by Irinotecan and Cisplatin in Patients With Limited-Disease Small-Cell Lung Cancer: West Japan Thoracic Oncology Group 9902

Author

Saito, Hiroshi, Takada, Yoshiki, Ichinose, Yukito, Eguchi, Kenji, Kudoh, Shinzoh, Matsui, Kaoru, Nakagawa, Kazuhiko, Takada, Minoru, Negoro, Shunichi, Tamura, Kenji, Ando, Masahiko, Tada, Takuhito, and Fukuoka, Masahiro

Published
2006
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28. Phase III Study of Docetaxel Compared With Vinorelbine in Elderly Patients With Advanced Non–Small-Cell Lung Cancer: Results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904)

Author

Kudoh, Shinzoh, Takeda, Koji, Nakagawa, Kazuhiko, Takada, Minoru, Katakami, Nobuyuki, Matsui, Kaoru, Shinkai, Tetsu, Sawa, Toshiyuki, Goto, Isao, Semba, Hiroshi, Seto, Takashi, Ando, Masahiko, Satoh, Taroh, Yoshimura, Naruo, Negoro, Shunichi, and Fukuoka, Masahiro

Published
2006
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32. Multi-Institutional Randomized Phase II Trial of Gefitinib for Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer

Author

Fukuoka, Masahiro, Yano, Seiji, Giaccone, Giuseppe, Tamura, Tomohide, Nakagawa, Kazuhiko, Douillard, Jean-Yves, Nishiwaki, Yutaka, Vansteenkiste, Johan, Kudoh, Shinzoh, Rischin, Danny, Eek, Richard, Horai, Takeshi, Noda, Kazumasa, Takata, Ichiro, Smit, Egbert, Averbuch, Steven, Macleod, Angela, Feyereislova, Andrea, Dong, Rui-Ping, and Baselga, José

Published
2003

34. Molecular Epidemiological Study on Passive Smoking and Estrogen Receptor Expression in Never-smokers with Non-small Cell Lung Cancer

Author

Yoshimoto, Naoki, Kawaguchi, Tomoya, Isa, Shun-ichi, Shimizu, Shigeki, Tamiya, Akihiro, Asai, Kazuhisa, Kudoh, Shinzoh, and Hirata, Kazuto

Subjects
Epidermal growth factor receptor mutations, 肺がん, 受動喫煙, Passive smoking, Never-smokers, Lung cancer, Estrogen, respiratory tract diseases
Abstract

Background : Although sex hormones are thought to play an important role in the carcinogenesis of non-small cell lung cancer (NSCLC) in never-smokers, the causative mechanism remains unknown. Passive smoking (PS) is common among East Asian women and has been suggested to be a potential cause of the disease. / Methods : We systematically evaluated the expression of estrogen receptor (ER), the prevalence of PS, and genetic mutations using tumor samples from a prospectively registered cohort of never-smokers with lung cancer. The study enrolled 92 never-smokers with NSCLC. Expression of ERα, ERβ, and progesterone receptor (PR) was examined via immunohistochemical staining (IHC). Detailed PS information was obtained through a standardized questionnaire. The cumulative dose of PS (CPS) was evaluated as a sum of the number of exposure years at home and/or in the work place....

Published
2016

37. Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer

Author

Suzumura Tomohiro, Kimura Tatsuo, Kudoh Shinzoh, Umekawa Kanako, Nagata Misato, Matsuura Kuniomi, Tanaka Hidenori, Mitsuoka Shigeki, Yoshimura Naruo, Kira Yukimi, Nakai Toshiyuki, and Hirata Kazuto

Subjects
CYP2D6, Non-small cell lung cancer, Gefitinib, Erlotinib, Adverse events, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Rash, liver dysfunction, and diarrhea are known major adverse events associated with erlotinib and gefitinib. However, clinical trials with gefitinib have reported different proportions of adverse events compared to trials with erlotinib. In an in vitro study, cytochrome P450 (CYP) 2D6 was shown to be involved in the metabolism of gefitinib but not erlotinib. It has been hypothesized that CYP2D6 phenotypes may be implicated in different adverse events associated with gefitinib and erlotinib therapies. Methods The frequency of each adverse event was evaluated during the period in which the patients received gefitinib or erlotinib therapy. CYP2D6 phenotypes were determined by analysis of CYP2D6 genotypes using real-time polymerase chain reaction techniques, which can detect single-nucleotide polymorphisms. The CYP2D6 phenotypes were categorized into 2 groups according to functional or reduced metabolic levels. In addition, we evaluated the odds ratio (OR) of the adverse events associated with each factor, including CYP2D6 activities and treatment types. Results A total of 232 patients received gefitinib therapy, and 86 received erlotinib therapy. Reduced function of CYP2D6 was associated with an increased risk of rash of grade 2 or more (OR, 0.44; 95% confidence interval [CI], 0.21–0.94; *p = 0.03), but not diarrhea ≥ grade 2 (OR, 0.49; 95% CI, 0.17–1.51; *p = 0.20) or liver dysfunction ≥ grade 2 (OR, 1.08; 95% CI, 0.52–2.34; *p = 0.84) in the gefitinib cohort. No associations were observed between any adverse events in the erlotinib cohort and CYP2D6 phenotypes (rash: OR, 1.77; 95% CI, 0.54–6.41; *p = 0.35/diarrhea: OR, 1.08; 95% CI, 0.21–7.43; *p = 0.93/liver dysfunction: OR, 0.93; 95% CI, 0.20–5.07; *p = 0.93). Conclusions The frequency of rash was significantly higher in patients with reduced CYP2D6 activity who treated with gefitinib compared to patients with functional CYP2D6. CYP2D6 phenotypes are a risk factor for the development of rash in response to gefitinib therapy.

Published
2012
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40. The Macroscopic Appearance of Computed Tomography-guided Needle Biopsy Specimens Correlates with Tumor Metastasis in Non-small Cell Lung Cancer

Author

Nakai, Toshiyuki, Kimura, Tatsuo, Suzumura, Tomohiro, Yoshimoto, Naoki, Oka, Takako, Yamamoto, Norio, Matsuura, Kuniomi, Mitsuoka, Shigeki, Asai, Kazuhisa, Tochino, Yoshihiro, Yoshimura, Naruo, Kawaguchi, Tomoya, Kudoh, Shinzoh, Matsuoka, Toshiyuki, Ohsawa, Masahiko, and Hirata, Kazuto

Subjects
Non-small cell lung cancer, Computed tomography (CT)-guided needle biopsy, Tumor metastasis
Abstract

Background : Computed tomography (CT)-guided needle biopsy is a well-established and dependable procedure for the diagnosis of pulmonary lesions. Some tissue biopsy samples have loose cohesion and disintegrate into tiny pieces before formalin fixation. The purpose of this study was to assess the association between the fresh macroscopic appearance of samples obtained using CT-guided needle biopsy and the clinicopathological features of non-small cell lung cancer (NSCLC). / Methods : A total of 111 patients who underwent CT-guided lung needle biopsy at Osaka City University Hospital between May 2009 and May 2013 were enrolled. Macroscopic appearance was categorized as either loose or tight cohesion. Samples were evaluated using Azan staining to detect collagen fibers. The staining intensity was multiplied by the percentage of positive cells, and the specimen was categorized as having either low (

Published
2015

42. Reaction of Plasma Adiponectin Level in Non-small Cell Lung Cancer Patients Treated with EGFR-TKIs

Author

Umekawa, Kanako, Kimura, Tatsuo, Kudoh, Shinzoh, Suzumura, Tomohiro, Nagata, Misato, Mitsuoka, Shigeki, Matsuura, Kuniomi, Oka, Takako, Yoshimura, Naruo, Kira, Yukimi, and Hirata, Kazuto

Subjects
Adipokines, Adiponectin, NSCLC, EGFR-TKIs, respiratory tract diseases
Abstract

Background : Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are routinely used to treat advanced non-small cell lung cancer (NSCLC) patients with activated EGFR mutations, and are associated with excellent response and improvement of performance status. Adipose tissue produces and releases substances called adipokines, which include adiponectin, leptin, resistin, and hepatocyte growth factor (HGF), etc. Previously, we reported that high levels of plasma HGF at diagnosis indicated intrinsic resistance to EGFR-TKIs. EGFR-TKIs have been hypothesized to affect these adipokines. / Methods : This prospective study, to evaluate the correlation between plasma adiponectin and insulin levels and non-hematological adverse effects in advanced NSCLC following EGFR-TKIs administration, was conducted at the Osaka City University Hospital. Plasma adiponectin and insulin levels were determined at diagnosis and on treatment day 30....

Published
2013

43. Skeletal-related Events in Advanced Lung Adenocarcinoma Patients Evaluated EGFR Mutations

Author

Nagata, Misato, Kudoh, Shinzoh, Mitsuoka, Shigeki, Suzumura, Tomohiro, Umekawa, Kanako, Tanaka, Hidenori, Matsuura, Kuniomi, Kimura, Tatsuo, Yoshimura, Naruo, and Hirata, Kazuto

Subjects
Non-small cell lung cancer, Skeletal-related event, Bone metastasis, EGFR mutation, Adenocarcinoma, respiratory tract diseases
Abstract

Background : The rate of lung cancer metastasis to the bone is high and skeletal-related events (SREs) decrease the quality of life in many patients. Recently, it was found that a subgroup of patients with non-small cell lung cancer (NSCLC) have specific mutations in the EGFR (epidermal growth factor receptor) gene. We assessed the SREs in advanced lung adenocarcinoma patients that evaluated EGFR mutations in whom bone metastasis was present. / Methods : We retrospectively investigated the clinical records of 377 patients with advanced NSCLC. Patients were evaluated for the presence of EGFR mutations, bone metastases, the incidence of SREs, and treatment history before the first SRE....

Published
2013

44. Comparison of Adverse Events of Erlotinib with those of Gefitinib in Patients with Non-small Cell Lung Cancer : A Case-control Study in a Japanese Population

Author

Suzumura, Tomohiro, Kimura, Tatsuo, Kudoh, Shinzoh, Umekawa, Kanako, Nagata, Misato, Tanaka, Hidenori, Mitsuoka, Shigeki, Yoshimura, Naruo, Kira, Yukimi, and Hirata, Kazuto

Subjects
Non-small cell lung cancer, Erlotinib, Adverse events, heterocyclic compounds, Gefitinib, skin and connective tissue diseases, neoplasms, respiratory tract diseases
Abstract

Background : Rash, liver dysfunction, and diarrhea are known as adverse events of erlotinib and gefitinib. However, clinical trials with gefitinib have reported different adverse events compared to those with erlotinib. In an in vitro study, cytochrome P450 (CYP) 2D6 was shown to be involved in the metabolism of gefitinib and not of erlotinib. It has been hypothesized that gefitinib therapy results in different adverse events compared to erlotinib therapy. / Methods : The frequency of each adverse event was evaluated in a case-control study on Japanese patients who were treated with gefitinib or erlotinib. The CYP2D6 phenotype was categorized into 2 groups according to functional or reduced metabolic levels. In addition, we evaluated the odds ratio (OR) of adverse events with each factor, including CYP2D6 activities as well as treatment types....

Published
2012

45. Clinical Outcome of Amrubicin Therapy According to the Prior Chemotherapy Sensitivities of Extensive Small Cell Lung Cancer

Author

Mitsuoka, Shigeki, Kudoh, Shinzoh, Kimura, Tatsuo, Yoshimura, Naruo, Tanaka, Hidenori, Suzumura, Tomohiro, Umekawa, Kanako, Nagata, Misato, Ueda, Takako, and Hirata, Kazuto

Subjects
Refractory, 肺がん, Lung cancer, Second-line chemotherapy, Amrubicin, Topoisomerase II inhibitor
Abstract

Background : Amrubicin (AMR) is an active agent for relapsed small cell lung cancer (SCLC). However, the activity of AMR in refractory relapsed patients is controversial. The objective of this retrospective analysis was to evaluate the efficacy and safety of AMR as second-line chemotherapy in SCLC, especially refractory relapsed SCLC. / Methods : Between July 2003 and February 2009, a total of 27 patients were treated with AMR at a dosage of 40 mg・m^-2・day^-1 on days 1-3 every 3 weeks. Safety was assessable for all patients. Efficacy was evaluated in 26 patients (one patient was not assessable for response), in 12 patients with chemotherapy-sensitive relapse and 14 patients with chemotherapy-refractory relapse. Sensitive relapse means that a first-line response lasted more than 90 days. Refractory relapse means that either did not respond to first-line chemotherapy or responded initially but relapsed within 90 days....

Published
2011

46. Effects of Tiotropium or Combined Therapy with Salmeterol on Hyperinflation in COPD

Author

Eguchi, Yohsuke, Tateishi, Yoshitaka, Umeda, Nobuaki, Yoshikawa, Takahiro, Kamoi, Hiroshi, Kanazawa, Hiroshi, Kudoh, Shinzoh, Hirata, Kazuto, and Fujimoto, Shigeo

Subjects
Inspiratory capacity, Tiotropium, Hyperinflation, Airflow obstruction, Salmeterol, respiratory tract diseases
Abstract

Background : Hyperinflation is widely accepted as an abnormal state affecting clinical symptoms, activities of daily living and exercise tolerance in chronic obstructive pulmonary disease (COPD). Reducing hyperinflation is an essential theme in COPD treatment. In this study, we let patients with COPD hyperventilate to evoke hyperinflation, and evaluated the effects of tiotropium alone or in combination with salmeterol on hyperventilation-evoked hyperinflation. / Methods : Thirty-eight patients with COPD received pulmonary function tests including hyperventilation-evoked hyperinflation testing and the St. George's Respiratory Questionnaire (SGRQ) before treatment, after tiotropium administration for 8 weeks, and after combined therapy with salmeterol for 8 weeks....

Published
2007

47. Smoking History and Prior Surgical Resection Predict Sensitivity to Gefitinib in Advanced Non-Small-Cell Lung Cancer

Author

Matsuura, Kuniomi, Kudoh, Shinzoh, Yoshimura, Naruo, Kimura, Tatsuo, Mitsuoka, Shigeki, Hirata, Kazuto, Yoshikawa, Junichi, and Iwao, Hiroshi

Subjects
Non-small cell lung cancer, Gefitinib, Prognostic factors, Predictive factors, respiratory tract diseases
Abstract

Background : Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase, and induces radiographic regression and symptomatic improvement in patients with non-small cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response, never smoking history and adenocarcinoma were associated with survival. We attempted to identify additional clinical features associated with response and survival. / Methods : We reviewed medical records and imaging studies of all 68 NSCLC patients treated by gefitinib monotherapy in our institution. We identified patients experiencing disease control and compared their clinical features with those of other patients....

Published
2006

48. A phase II, multicenter, single-arm trial of eribulin as first-line chemotherapy for HER2-negative locally advanced or metastatic breast cancer.

Author

Takashima, Tsutomu, Tokunaga, Shinya, Tei, Seika, Nishimura, Shigehiko, Kawajiri, Hidemi, Kashiwagi, Shinichiro, Yamagata, Shigehito, Noda, Satoru, Nishimori, Takeo, Mizuyama, Yoko, Sunami, Takeshi, Tezuka, Kenji, Ikeda, Katsumi, Ogawa, Yoshinari, Onoda, Naoyoshi, Ishikawa, Tetsuro, Kudoh, Shinzoh, Takada, Minoru, and Hirakawa, Kosei

Published
2016
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50. Plasma RANTES, IL-10, and IL-8 levels in non-small-cell lung cancer patients treated with EGFR-TKIs.

Author

Umekawa, Kanako, Kimura, Tatsuo, Kudoh, Shinzoh, Suzumura, Tomohiro, Oka, Takako, Nagata, Misato, Mitsuoka, Shigeki, Matsuura, Kuniomi, Nakai, Toshiyuki, Yoshimura, Naruo, Kira, Yukimi, and Hirata, Kazuto

Subjects
EPIDERMAL growth factor receptors, PROTEIN-tyrosine kinase inhibitors, LUNG cancer, T cells, INFLAMMATION, CANCER patients, HEALTH outcome assessment
Abstract

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), routinely used to treat advanced non-small-cell lung cancer (NSCLC) patients with activated EGFR mutations, are associated with excellent response and improved performance status. Recently, pro-inflammatory cytokines, such as regulated upon activation normal T cell expressed and secreted (RANTES), interleukin (IL)-10 and IL-8 have been proposed as mediators of cancer development. EGFR-TKIs have been found to affect this network of pro-inflammatory cytokines. Methods: EGFR-TKIs (erlotinib, 150 mg/day; and gefitinib, 250 mg/day) were administered once per day. Treatment was continued until disease progressed or the patient developed intolerable symptoms of toxicity, or withdrew his/her consent for study participation. The treatment was a part of standard care. We investigated the correlation between plasma pro-inflammatory cytokines (including plasma RANTES, IL-10, and IL-8) levels and clinical outcomes following EGFR-TKI treatment in lung cancer patients. Pro-inflammatory cytokine levels were evaluated at diagnosis and on treatment day 30 after the first administration of EGFR-TKIs. Results: Overall, 33 patients were enrolled. Plasma pro-inflammatory cytokine levels were determined for all patients at diagnosis. Plasma samples from 26 patients were obtained on treatment day 30. High level of RANTES at diagnosis was associated with severe general fatigue (P = .026). Low level of RANTES at diagnosis was significantly associated with long-term survival (P = .0032). Percent decrease change of IL-10 was associated with severity of rash (P = .037). The plasma IL-8 level on treatment day 30 (median, 5.48 pg/mL; range, 0.49-26.13 pg/mL) was significantly lower than the level at diagnosis (median 10.45 pg/mL; 3.04-54.86 pg/mL; P = .021). Conclusions: These results suggest that EGFR-TKIs may suppress systemic inflammation and promote tumor shrinkage. The network of pro-inflammatory cytokines was affected by EGFR-TKI treatment for NSCLC. In addition, the clinical outcomes of EGFR-TKI treatment were influenced by the status of the plasma pro-inflammatory cytokines at diagnosis. [ABSTRACT FROM AUTHOR]

Published
2013
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