Phase I study of irinotecan and gemcitabine in previously untreated patients with advanced non-small cell lung cancer.
Hiroshi Takatani, Hiroshi Soda, Yoichi Nakamura, Akitoshi Kinoshita, Masaaki Fukuda, Seiji Nagashima, Minoru Fukuda, Yoshifumi Soejima, Hirofumi Nakano, Mikio Oka, Shigeru Kohno
(Department of Internal Medicine, Nagasaki Municipal Hospital, Nagasaki, Japan.)
Jpn. J. Clin. Oncol.
irinotecan and gemcitabine are effective against non-small_cell lung cancer we_conducted phase study of the combined use of irinotecan and gemcitabine in previously_untreated patients with advanced_non-small cell lung cancer to determine dose-limiting_toxicities and maximum_tolerated dose patients were treated with irinotecan followed_by gemcitabine on days and every_weeks gemcitabine dose was fixed at mg/m2 and irinotecan dose was increased from mg/m2 total of patients was enrolled maximum_tolerated dose of irinotecan was determined up to level irinotecan_mg/m2 in japan the maximum approved weekly dose of irinotecan is mg/m2 so this was the dose that was used only very mild hematological and non-hematological_toxicities were noted use of mg/m2 irinotecan followed_by mg/m2 gemcitabine on days and every_weeks warrants phase_ii study
High EGFR copy number predicts benefits from tyrosine kinase inhibitor treatment for non-small cell lung cancer patients with wild-type EGFR.
Fang Wang, Sha Fu, Qiong Shao, Yan-Bin Zhou, Xiao Zhang, Xu Zhang, Cong Xue, Jian-Guang Lin, Li-Xia Huang, Li Zhang, Wei-Min Zhang, Jian-Yong Shao
()
J Transl Med
this_study was designed to determine_whether advanced_non-small-cell lung cancer nsclc patients with high copy_number of epidermal_growth factor_receptor egfr can benefit_from treatment with egfr-tyrosine_kinase inhibitors_tkis egfr gene_copy number was assessed by fluorescence in situ_hybridization fish and egfr_mutations was tested using luminex xtag technology in tki-treated nsclc patients the association_between both biomarkers and clinical_benefit from egfr-tki were analyzed egfr fish+and egfr_mutations were significantly associated with higher response_rates and respectively superior progression-free_survival pfs fish+ months hazard_ratio hr_ci to mutation+ months hr_ci to and overall_survival os fish+ months hr_ci to mutation+ months hr_ci to in patients with wild-type_egfr egfr fish+correlated with longer_pfs than egfr fish status months vs months hr_ci to so did amplification months vs months hr_ci to however fish+had no association with improved pfs in egfr-mutated patients hr_ci to combined analysis of egfr fish and mutation is an effective predictor of egfr-tki therapy specifically high egfr copy_number may predict benefit_from tkis
Different efficacies of erlotinib and gefitinib in taiwanese patients with advanced non-small cell lung cancer: a retrospective multicenter study.
Wen-Chien Fan, Chong-Jen Yu, Chun-Ming Tsai, Ming-Shyan Huang, Chun-Liang Lai, Te-Chun Hsia, Yin-Jing Tien, Shiang-Fen Huang, Chieh-Hung Wu, Kun-Ta Chou, Yu-Chin Lee, Reury-Perng Perng, Yuh-Min Chen
(Department of Medicine, Chutung Veterans Hospital, Chutung, Taiwan.)
J Thorac Oncol
epidermal_growth factor_receptor-tyrosine kinase_inhibitors are used as effective first-line and salvage_therapy in the treatment of advanced_non-small cell lung cancer nsclc patients in east_asia the objective of this_study was to compare the efficacy of gefitinib and erlotinib in taiwanese patients with advanced_nsclc clinical data of nsclc patients treated with gefitinib or erlotinib from_january to december were collected retrospectively five tertiary_referral centers in taiwan participated in the study of the patients enrolled were female were never_smokers or former light_smokers and were diagnosed with adenocarcinoma epidermal_growth factor_receptor-tyrosine kinase_inhibitors were prescribed as first-line_treatment in patients and as second-line or salvage_therapy in patients the objective_response rate was similar between the gefitinib and erlotinib treatment groups while disease control rate was and respectively median_progression-free survival of gefitinib and erlotinib groups was and months respectively median overall_survival of gefitinib and erlotinib groups was and months respectively taiwanese patients with advanced_nsclc treated with erlotinib reported higher disease control rate longer_progression-free survival and overall_survival compared with patients treated with gefitinib
Excision repair cross-complementation group 1 predicts progression-free and overall survival in non-small cell lung cancer patients treated with platinum-based chemotherapy.
Koichi Azuma, Yoshihiro Komohara, Tetsuro Sasada, Yasuhiro Terazaki, Jiro Ikeda, Tomoaki Hoshino, Kyogo Itoh, Akira Yamada, Hisamichi Aizawa
(Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. azuma@med.kurume-u.ac.jp)
Cancer Sci.
expression of excision_repair cross-complementation_group ercc1 p53 or thioredoxin_trx is reported to be correlated with resistance to platinum-based drugs the authors evaluated whether ercc1 p53 or trx expression could predict progression-free and/or overall_survival in relapsed non-small_cell lung cancer nsclc patients treated with platinum-based_chemotherapy immunohistochemistry was used to examine the expression of these three proteins in resected lung tumor samples obtained_from patients treated with platinum-based_chemotherapy against recurrent tumors after curative_resection immunostaining for ercc1 p53 and trx was positive in and patients respectively patients negative for ercc1 had significantly_longer median_progression-free vs weeks and overall vs weeks survival than_those positive for ercc1 patients negative for p53 expression had significantly_longer median overall vs weeks but_not progression-free vs weeks survival than_those positive for p53 expression from multivariate_analysis negative ercc1 expression hazard_ratio hr was significantly favorable factor for progression-free_survival and negative ercc1 expression hr and better performance_status hr were significantly favorable factors for overall_survival this retrospective_study indicates_that immunostaining for ercc1 may_be useful for predicting survival in nsclc patients receiving_platinum-based chemotherapy against recurrent tumors after curative_resection and can provide critical information for planning personalized chemotherapy
De novo resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in EGFR mutation-positive patients with non-small cell lung cancer.
Masayuki Takeda, Isamu Okamoto, Yoshihiko Fujita, Tokuzo Arao, Hiroyuki Ito, Masahiro Fukuoka, Kazuto Nishio, Kazuhiko Nakagawa
(Department of Medical Oncology, Kinki University School of Medicine, Osaka-Sayama, Osaka, Japan.)
J Thorac Oncol
somatic_mutations in the epidermal_growth factor_receptor egfr gene are predictor of response to treatment with egfr_tyrosine kinase_inhibitors tkis in patients with non-small_cell lung cancer nsclc however mechanisms of de_novo resistance to these drugs in patients harboring_egfr mutations have remained_unclear we_examined whether the mutational_status of kras might_be associated with primary resistance to egfr-tkis in egfr_mutation-positive patients with nsclc forty patients with nsclc with egfr_mutations who were treated with gefitinib or erlotinib and had archival_tissue specimens available were enrolled in the study kras_mutations were analyzed by direct_sequencing three of the patients had progressive_disease and two of these three individuals had both kras and egfr_mutations our_results suggest_that kras_mutation is negative predictor of response to egfr-tkis in egfr_mutation-positive patients with nsclc
Comparative analysis of epidermal growth factor receptor mutations and gene amplification as predictors of gefitinib efficacy in Japanese patients with nonsmall cell lung cancer.
Takashi Sone, Kazuo Kasahara, Hideharu Kimura, Kazuto Nishio, Masayuki Mizuguchi, Yasuto Nakatsumi, Kazuhiko Shibata, Yuko Waseda, Masaki Fujimura, Shinji Nakao
(Respiratory Medicine, School of Medicine, Kanazawa University, Kanazawa, and Shien-Lab, National Cancer Center Hospital, Tokyo, Japan.)
Cancer
because the investigation of epidermal_growth factor_receptor gene egfr status as predictor of gefitinib efficacy in japanese patients has shown_promise the authors evaluated egfr_mutations and gene_amplification in biopsy_specimens from japanese patients with nonsmall_cell lung cancer nsclc who_received treatment with gefitinib to analyze the correlation_between egfr gene status and clinical_outcome fifty-nine patients were enrolled in this_study egfr gene_amplification was evaluated by fluorescence in situ_hybridization fish and egfr_mutations in exons and were analyzed by polymerase_chain reaction and direct_sequencing egfr_mutations were detected in patients fish-positive results were observed in patients the response_rate was significantly_higher in the patients with egfr_mutations than in the patients without mutations vs no_significant difference in the response_rate was observed between fish-positive patients and fish-negative patients vs egfr_mutation was correlated with both longer time to progression_ttp months vs months and longer overall_survival os months vs months no_significant differences in ttp or os were observed between fish-positive patients andfish-negative patients the results from multivariate_analysis indicated_that egfr_mutations maintained significant_association with longer_ttp and longer os the results of this_study suggested_that egfr_mutations may_serve as predictors of response and survival and that the role of egfr gene_amplification is not predictor of gefitinib efficacy in japanese patients with
Multicenter, randomized trial for stage IIIB or IV non-small-cell lung cancer using weekly paclitaxel and carboplatin followed by maintenance weekly paclitaxel or observation.
Chandra P Belani, John Barstis, Michael C Perry, Renato V La Rocca, Sreenivasa R Nattam, David Rinaldi, Ray Clark, Glenn M Mills
(University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA. belanicp@msx.upmc.edu.)
J. Clin. Oncol.
to explore the efficacy and safety of three regimens of weekly_paclitaxel plus_carboplatin as initial therapy and the feasibility of subsequent maintenance_therapy versus observation in patients with advanced_non-small-cell lung cancer nsclc four_hundred one patients were randomly_assigned to one of the following arms arm paclitaxel_mg/m2 weekly for of weeks with carboplatin_area under the curve_auc on_day arm paclitaxel_mg/m2 and carboplatin_auc weekly for of weeks or arm paclitaxel_mg/m2 cycle and mg/m2 cycle and carboplatin_auc weekly for of weeks patients who_responded at week were randomly_assigned to either weekly_paclitaxel therapy mg/m2 of weeks or observation for the assessable patients the objective_response rates observed with initial therapy were for arm for arm and for arm the median time to progression and median_survival times were and weeks for arm and weeks for arm and and weeks for arm respectively the 1-year_survival rates were for arm for arm and for arm arm paclitaxel_mg/m2 weekly for of weeks with carboplatin_auc administered on_day demonstrates the most favorable therapeutic_index in patients with advanced_nsclc
[Feasibility of erlotinib after gefitinib failure in patients with advanced pulmonary adenocarcinoma previously responding to gefitinib].
Zi-jin Zhang, Ping Zhang, Xiao-nan Wu, Lin Li, Gang Cheng
(Department of Medical Oncology, Beijing Hospital, Beijing 100730, China.)
Zhongguo Yi Xue Ke Xue Yuan Xue Bao
to evaluate the efficacy and progression-free_survival of erlotinib after progression of disease to gefitinib in patients with advanced pulmonary adenocarcinoma who previously obtained disease control with gefitinib in this retrospective_study patients with advanced or metastatic pulmonary adenocarcinoma who were previously obtained partial_response or stable_disease with gefitinib were treated with erlotinib after gefitinib failure erlotinib efficiency progression-free_survival and overall_survival were analyzed nice achieved stable_disease and three achieved progression disease with erlotinib treatment after gefitinib failure no complete_response or partial_response was observed the disease control rate was the median_progression-free survival and overall_survival of erlotinib were days and days erlotinib seems to be an optional treatment after gefitinib failure for advanced pulmonary adenocarcinoma patients who previously responded to gefitinib
Salvage treatment of advanced non-small-cell lung cancer previously treated with docetaxel-based front-line chemotherapy with irinotecan (CPT-11) in combination with cisplatin.
S Kakolyris, C Kouroussis, K Kalbakis, D Mavroudis, J Souglakos, Nvardakis, S Kremos, V Georgoulias
(Department of Medical Oncology, School of Medicine, University General Hospital of Heraklion, Crete, Greece. georgoul@med.uch.gr)
Ann. Oncol.
phase_ii study was conducted in order to determine the toxicity and efficacy of the combination of cpt-11 and cisplatin as salvage treatment in patients with advanced_non-small-cell lung cancer nsclc progressing_after docetaxel-based front-line regimen thirty-one patients median_age years with nsclc were enrolled twenty-six patients were male twenty-five had disease stage_iv and twenty-eight had performance_status who 0-1 cpt-11 was administered as 60-minute infusion at the dose of mg/m2 on_day and mg/m2 on_day cisplatin was administered at the dose of mg/m2 on_day after cpt-11 administration treatment was repeated_every three weeks total of chemotherapy cycles were administered in an_intention-to-treat analysis patients introduction confidence_interval ci achieved_partial response had_stable disease and progressive_disease three of responders had failed_previous docetaxel-carboplatin combination the median_duration of response was months the median_ttp months and the median_survival for the entire_group months grade_3-4 neutropenia was observed in patients and in two cases this was febrile grade and thrombocytopenia_occurred in two patients respectively grade and diarrhea was seen in patients grade_2-3 neurotoxicity in and fatigue grade_2-3 in other toxicities were mild the combination of cpt-11 and cisplatin has manageable_toxicity and interesting activity as salvage treatment of patients with advanced_nsclc previously_treated with docetaxel-based front-line regimen
A phase II study of vinorelbine, mitomycin C and cisplatin chemotherapy for advanced non-small cell lung cancer.
Mi Ran Kwon, Tae Yeob Jeong, Young Jin Yuh, Sung Rok Kim
(Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea. tufmr@hanmail.net)
Korean J. Intern. Med.
this prospective phase_ii trial was performed to determine the efficacy and toxicity of mitomycin vinorelbine and cisplatin combination chemotherapy for patients with previously_untreated stage_iiib or iv non-small_cell lung cancer nsclc between_january and april patients with chemotherapy-naive stage_iiib or iv nsclc were entered_into this_study mitomycin at dose of mg/m2 vinorelbine at dose of mg/m2 and cisplatin at dose of mg/m2 on_day and vinorelbine at dose of mg/m2 on_day were administered this regimen was repeated_every weeks patients out of patients were assessable among the assessable patients patients had partial_response the median_duration of response and survival was weeks and weeks respectively grade or leukopenia and thrombocytopenia were observed in and of all the cycles respectively nausea and vomiting of grade occurred only in of all the cycles the regimen of mitomycin vinorelbine and cisplatin for non-small_cell lung cancer is active_against advanced_nsclc with tolerable toxicities