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1.
J Clin Oncol ; 28(23): 3739-45, 2010 Aug 10.
Article in English | MEDLINE | ID: mdl-20625120

ABSTRACT

PURPOSE: This phase III trial of concurrent thoracic radiotherapy (TRT) was conducted to compare third-generation chemotherapy with second-generation chemotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients received the following treatments: A (control), four cycles of mitomycin (8 mg/m(2) on day 1)/vindesine (3 mg/m(2) on days 1, 8)/cisplatin (80 mg/m(2) on day 1) plus TRT 60 Gy (treatment break for 1 week); B, weekly irinotecan (20 mg/m(2))/carboplatin (area under the plasma concentration-time curve [AUC] 2) for 6 weeks plus TRT 60 Gy, followed by two courses of irinotecan (50 mg/m(2) on days 1, 8)/carboplatin (AUC 5 on day 1); C, weekly paclitaxel (40 mg/m(2))/carboplatin (AUC 2) for 6 weeks plus TRT 60 Gy, followed by two courses of paclitaxel (200 mg/m(2) on day 1)/carboplatin (AUC 5 on day 1). RESULTS: The median survival time and 5-year survival rates were 20.5, 19.8, and 22.0 months and 17.5%, 17.8%, and 19.8% in arms A, B, and C, respectively. Although no significant differences in overall survival were apparent among the treatment arms, noninferiority of the experimental arms was not achieved. The incidences of grade 3 to 4 neutropenia, febrile neutropenia, and gastrointestinal disorder were significantly higher in arm A than in arm B or C (P < .001). Chemotherapy interruptions were more common in arm B than in arm A or C. CONCLUSION: Arm C was equally efficacious and exhibited a more favorable toxicity profile among three arms. Arm C should be considered a standard regimen in the management of locally advanced unresectable NSCLC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Radiotherapy, Adjuvant , Adult , Aged , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Combined Modality Therapy , Female , Humans , Irinotecan , Male , Middle Aged , Mitomycin/administration & dosage , Paclitaxel/administration & dosage , Vindesine/administration & dosage
2.
Nihon Kokyuki Gakkai Zasshi ; 47(5): 347-54, 2009 May.
Article in Japanese | MEDLINE | ID: mdl-19514493

ABSTRACT

Twenty-one patients (15 men, 6 women, median age 67) were given a diagnosis of malignant pleural mesothelioma between March 1998 and December 2007 in our hospital. There was apparent occupational exposure of asbestos in 11 patients and suspicion of asbestos exposure in 5. Mean period recuired for diagnosis was 60 days with VATS and percutaneous needle biopsy. Eight patients underwent pleuropneumonectomy. Their median survival was 14.4 months, and the 2-year survival rate was approximately 30%. Seven other patients received chemotherapy, another patient underwent palliative radiotherapy and the remaining 5 patients received best supportive care. One patient had long survived (41.6 months) with gemcitabine-based chemotherapy. In the Senshu district, in the southern part of Osaka, there have been many asbestos spinning mills, so environmental exposure might occur. We should try to diagnose malignant mesothelioma for patients with pleural effusion even if they apparently do not have a history of asbestos exposure.


Subject(s)
Asbestos/adverse effects , Mesothelioma/etiology , Mesothelioma/therapy , Occupational Exposure/adverse effects , Pleural Neoplasms/diagnosis , Pleural Neoplasms/therapy , Aged , Aged, 80 and over , Drug Therapy , Environmental Exposure/adverse effects , Female , Humans , Japan/epidemiology , Male , Mesothelioma/diagnosis , Mesothelioma/mortality , Middle Aged , Pleura/surgery , Pleural Neoplasms/etiology , Pleural Neoplasms/mortality , Pneumonectomy , Radiotherapy , Retrospective Studies , Survival Rate
3.
Jpn J Clin Oncol ; 39(2): 116-23, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19052038

ABSTRACT

OBJECTIVE: The Phase I dose-escalation study was conducted to evaluate the safety and pharmacokinetics of lapatinib (GW572016), a dual ErbB-1 and -2 inhibitor, in Japanese patients with solid tumors that generally express ErbB-1 and/or overexpress ErbB-2. METHODS: Patients received oral lapatinib once daily until disease progression or in an event of unacceptable toxicity. RESULTS: Twenty-four patients received lapatinib at dose levels of 900, 1200, 1600 and 1800 mg/day; six subjects enrolled to each dose level. The majority of drug-related adverse events was mild (Grade 1-2); the most common events were diarrhea (16 of 24; 67%), rash (13 of 24; 54%) and dry skin (8 of 24; 33%). No Grade 4 adverse event was observed. There were four Grade 3 drug-related adverse events in three patients (i.e. two events of diarrhea at 1600 and 1800 mg/day each and gamma-glutamyl transpeptidase increase at 1800 mg/day). The maximum tolerated dose was 1800 mg/day. The pharmacokinetic profile of lapatinib in Japanese patients was comparable to that of western subjects. CONCLUSIONS: Lapatinib was well tolerated at doses of 900-1600 mg/day in Japanese solid tumor patients. Overall, our findings were similar to those of overseas studies.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/pharmacokinetics , ErbB Receptors/antagonists & inhibitors , Protein-Tyrosine Kinases/antagonists & inhibitors , Quinazolines/administration & dosage , Quinazolines/pharmacokinetics , Receptor, ErbB-2/antagonists & inhibitors , Administration, Oral , Adult , Aged , Asian People , Humans , Japan , Lapatinib , Middle Aged
4.
J Thorac Oncol ; 3(2): 187-9, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18303442

ABSTRACT

Large cell neuroendocrine carcinoma (LCNEC) is a relatively new category of pulmonary neuroendocrine tumor. Although it was first detected in the lung, LCNEC has since been found in a variety of extrapulmonary sites. We now describe a patient who was diagnosed with LCNEC originating from the mediastinum, an extremely rare disorder. An increased serum concentration of alpha-fetoprotein (AFP) in the patient was reduced by chemotherapy in association with tumor shrinkage. Furthermore, the tumor was confirmed immunohistochemically to produce AFP. To our knowledge, this is the first report of a LCNEC that produces AFP.


Subject(s)
Carcinoma, Neuroendocrine/blood , Mediastinal Neoplasms/blood , alpha-Fetoproteins/metabolism , Adult , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/therapy , Humans , Male , Mediastinal Neoplasms/pathology , Mediastinal Neoplasms/therapy , Neoadjuvant Therapy , Tomography, X-Ray Computed
5.
Jpn J Thorac Cardiovasc Surg ; 54(7): 293-6, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16898643

ABSTRACT

An 82-year-old woman with monoclonal immunoglobulin (Ig) M-type paraproteinemia had a large opacity in the right lung field. The abnormal shadow on roentgenogram had persisted for more than 6 years since the initial diagnosis of paraproteinemia, which had been diagnosed as Waldenström's macroglobulinemia (WM). Computed tomography revealed the lesion as a pulmonary tumor which was finally diagnosed as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) after surgical removal. MALT lymphoma constitutes the majority of primary pulmonary lymphomas and is often associated with monoclonal IgM-type paraproteinemia as well as WM, a distinctive lymphoproliferative disorder. Pulmonary MALT lymphoma should frequently be suspected in case of an indeterminate pulmonary tumor with IgM-type paraproteinemia.


Subject(s)
Lung Neoplasms/secondary , Lymphoma, B-Cell, Marginal Zone/pathology , Waldenstrom Macroglobulinemia/pathology , Aged, 80 and over , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Lymphoma, B-Cell, Marginal Zone/diagnostic imaging , Lymphoma, B-Cell, Marginal Zone/surgery , Radiography, Thoracic , Thoracic Surgery, Video-Assisted , Thoracotomy , Tomography, X-Ray Computed , Waldenstrom Macroglobulinemia/diagnostic imaging , Waldenstrom Macroglobulinemia/surgery
6.
Anticancer Res ; 26(3B): 2479-85, 2006.
Article in English | MEDLINE | ID: mdl-16821636

ABSTRACT

BACKGROUND: A combination phase I study was conducted in a cohort of lung cancer patients to determine the maximum tolerated dose (MTD) and toxicities of irinotecan (CPT-11), a topoisomerase I inhibitor, in combination with amrubicin (AMR), a topoisomerase II inhibitor, and to observe their antitumor activities. PATIENTS AND METHODS: Patients with lung cancer received AMR (35 - 40 mg/m2 given intravenously over 5 min) for 3 consecutive days, and CPT-11 (50 - 60 mg/m2 given intravenously over 90 min) after the completion of AMR infusion on days 1 and 8, every 3 weeks. RESULTS: In total, eleven patients were enrolled in this study. The most frequent toxicities were bone marrow suppression, particularly leucopenia and neutropenia, followed by infection, diarrhea and pneumonitis. As a consequence of these toxicities, the MTD and the recommended dose could not be determined. There were two partial responses, which included one patient with small cell lung cancer (SCLC) who had previously received chemotherapy and the other with previously untreated non-small cell lung cancer (NSCLC). CONCLUSION: These data suggest that the combination of CPT-11 and AMR is not tolerated, as it mediates an unexpectedly strong myelosuppressive effect, and is inactive against both NSCLC and SCLC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lung Neoplasms/drug therapy , Aged , Anthracyclines/administration & dosage , Anthracyclines/adverse effects , Anthracyclines/pharmacokinetics , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/pharmacokinetics , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/metabolism , Female , Humans , Irinotecan , Lung Neoplasms/metabolism , Male , Middle Aged
7.
Cancer ; 107(3): 599-605, 2006 Aug 01.
Article in English | MEDLINE | ID: mdl-16804877

ABSTRACT

BACKGROUND: Combined gemcitabine and carboplatin (GC) and combined gemcitabine and vinorelbine (GV) are active and well tolerated chemotherapeutic regimens for patients with advanced nonsmall cell lung cancer (NSCLC). The authors conducted a randomized Phase II study of GC versus GV to compare them in terms of efficacy and toxicity. METHODS: One hundred twenty-eight patients with Stage IIIB or IV NSCLC were randomized to receive either carboplatin at an area under the curve of 5 on Day 1 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) or vinorelbine 25 mg/m2 combined with gemcitabine 1000 mg/m2 on Days 1 and 8 (n = 64 patients) every 3 weeks. RESULTS: Response rates were 20.3% for the GC patients and 21.0% for the GV patients. In the GC arm, the median survival was 432 days, and the a 1-year survival rate was 57.6%; in the GV arm, the median survival was 385 days, and the 1-year survival rate was 53.3% in the GV arm. The median progression-free survival was 165 days in the GC arm and 137 days in the GV arm. Severe hematologic toxicity (Grade 4) was significantly more frequent in the GC arm (45.3% vs. 25.8% in the GV arm; P = .022). Most notably, the incidence of Grade 3 or 4 thrombocytopenia was significantly higher in the GC arm (81.3% vs. 6.5% in the GV arm; P < .001). Conversely, severe nonhematologic toxicity (Grade 3 or 4) was more common in the GV arm (7.8% vs. 19.4% in the GC arm; P = .057). CONCLUSIONS: Although the GV and GC regimens had different toxicity profiles, there was no significant difference in survival among patients with NSCLC in the current study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Lung Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Adult , Aged , Carboplatin/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Japan , Male , Middle Aged , Neoplasm Staging , Patient Selection , Survival , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinorelbine , Gemcitabine
8.
J Thorac Oncol ; 1(3): 226-30, 2006 Mar.
Article in English | MEDLINE | ID: mdl-17409861

ABSTRACT

The purpose of this study was to investigate the maximum tolerated doses, dose-limiting toxicities, efficacy, and pharmacokinetic profiles in the combination of irinotecan and paclitaxel. Eligibility criteria included age 75 years or younger, good performance status, adequate organ function, and unresectable non-small cell or extensive disease of small cell lung cancer. Irinotecan was administered on days 1 and 8 over 90 minutes, and paclitaxel was administered on day 8 over 3 hours after 90 minutes from the end of the irinotecan infusion. Irinotecan and paclitaxel were dose-escalated from 40 and 135 mg/m and repeated every 4 weeks. The authors also administered a higher dosage with preventive granulocyte colony-stimulating factor support from day 9. Thirty-one patients were assessed for toxicities and responses. Dose-limiting toxicities were neutropenia and febrile neutropenia. The dose of irinotecan 60 mg/m and paclitaxel 200 mg/m with preventive granulocyte colony-stimulating factor support was tolerable and suitable for a phase II trial. Nine of 25 (36%) patients with non-small cell and all six patients with small cell carcinoma achieved partial response. The areas under the concentration versus time curves of irinotecan and its metabolites on day 8 were significantly higher than on day 1. This combination therapy must be planned only after careful consideration of the drug-drug interaction.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Carcinoma/drug therapy , Lung Neoplasms/drug therapy , Paclitaxel/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Area Under Curve , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/pharmacokinetics , Dose-Response Relationship, Drug , Female , Humans , Irinotecan , Male , Middle Aged , Paclitaxel/adverse effects , Paclitaxel/pharmacokinetics
9.
Lung Cancer ; 46(2): 247-54, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15474673

ABSTRACT

BACKGROUND: The purpose of the study was to identify the potential predictive features associated with the response and survival benefit of gefitinib administration. We have retrospectively reviewed data of all patients who received a single regimen of gefitinib in our institution from August 1998 until July 2003. METHODS: Overall 101 patients with non-small-cell lung cancer (NSCLC) who have received a single use of gefitinib were analyzed. Potential factors associated with the response of gefitinib included smoking index, gender, histology, performance status (PS), number of pre-treatments, age and stage. Univariate analysis was performed for these strata by Fisher's exact test and multivariate analysis was then performed using the logistic regression model. RESULTS: The overall response rate was 19.8%. Univariate analysis revealed that significant predictive factors were associated with the response for 'adenocarcinoma', 'female', 'good PS' (0-l) and 'non-smoker' categories. Multivariate analysis limited the predictive factors associated with the response for 'female' (P = 0.0032), 'good PS' (P < 0.02) and 'non-smoker' (P = 0.0417). In survival analyses, 'female' (P < 0.005), 'good PS' (P < 0.0001), and a low level of the smoking index (P < 0.05) indicated significantly prolonged survival. Response and survival data in elderly patients were equivalent to those in younger patients. Adverse events (AEs) were generally mild and were almost always skin reactions and diarrhea. Interstitial lung disease (ILD) occurred in 4% of the group under observation. CONCLUSIONS: Gefitinib provided clinical benefit for the following factors 'female', 'good PS' and 'non-smoker'. A low smoking index is reported as a novel predictive prognostic factor following a single regimen of gefitinib.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Quinazolines/therapeutic use , Adult , Age Factors , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Female , Gefitinib , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Retrospective Studies , Sex Factors , Smoking/adverse effects , Survival Analysis , Treatment Outcome
10.
Lung Cancer ; 38(3): 303-8, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12445753

ABSTRACT

A phase II study was conducted to assess the activity and toxicity of irinotecan (CPT-11) and carboplatin (CBDCA) combination chemotherapy for advanced non-small-cell lung cancer (NSCLC). Eligibility included chemo-naive advanced NSCLC patients with measurable disease and a good performance status. CPT-11 of 50 mg/m(2) was administered as a 90-min intravenous infusion on days 1, 8, and 15. CBDCA dosed to an area under the concentration-time curve of 5 mgmin/ml, using Calvert's formula, was administered by 90-min infusion after the CPT-11 infusion on day 1. Treatment was repeated 28 days interval for at least two cycles. Haematopoietic growth factors were not routinely used. From December 1997 to January 1999, 36 patients were entered into the study. The overall response rate was 25.0% (95% confidence interval: 12.1-42.2%). The median survival time and the 1-year survival rate were 10.2 months and 42.2%, respectively. Major toxicity by Japan Clinical Oncology Group criteria was as follows: grade 3-4 neutropenia 76.5%; grade 3 anemia 26.5%; grade 3/4 thrombocytopenia 47.1%; grade 3 nausea/vomiting 36.1%; grade 3-4 diarrhoea 5.9%; grade 3 alopecia 5.9%; grade 3-4 skin rush 2.9%. Four patients developed febrile neutropenia and only one had serious diarrhea induced by CPT-11. Actual relative delivery dose of CPT-11 to the projected one on days 8 and 15 were 0.86 and 0.43, respectively. It seemed that CPT-11 and CBDCA was more toxic regimen than CPT-11 and CDDP in advanced NSCLC. The relatively disappointing response rate could be related with low dose intensity of CPT-11.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Dose-Response Relationship, Drug , Female , Humans , Infusions, Intravenous , Irinotecan , Lung Neoplasms/pathology , Male , Middle Aged , Survival Rate , Treatment Outcome
11.
Lung Cancer ; 35(3): 299-304, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11844605

ABSTRACT

Reverse transcription polymerase chain reaction (RT-PCR) single-strand conformation polymorphism analysis was used to detect topoisomerase I (top1) mutations in total RNA from 16 specimens that were excised during surgery from eight patients with non-small cell lung cancer (NSCLC) who had received preoperative chemotherapy consisting of irinotecan (CPT-11) and cisplatin. PCR single-strand conformation polymorphism and subsequent DNA sequencing analysis showed two nucleotide substitutions resulting in Trp736stop (TGG to TGA) and Gly737Ser (GGT to AGT) in one tumor specimen. The mutations were located near a site in top1 that was previously reported to harbor a mutation in the human lung cancer cell line PC7/CPT, which was selected for CPT resistance. These results demonstrate that mutations in top1 occur after chemotherapy with CPT-11 in NSCLC patients and suggest that development of resistance to CPT-11 in some patients may involve mutation of top1. However, the significance of top1 mutations to CPT resistance needs to be further investigated.


Subject(s)
Camptothecin/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , DNA Topoisomerases, Type I/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Point Mutation/genetics , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/pharmacology , Combined Modality Therapy , DNA, Neoplasm/analysis , DNA, Neoplasm/genetics , Female , Humans , Irinotecan , Male , Middle Aged , Mutagenesis/drug effects , Polymorphism, Single-Stranded Conformational , RNA, Messenger/analysis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction
12.
Lung Cancer ; 35(1): 11-6, 2002 Jan.
Article in English | MEDLINE | ID: mdl-11750707

ABSTRACT

Recently, several studies have suggested that a major mechanism of resistance to paclitaxel might involve mutations in the beta-tubulin gene in tumor cells. To investigate the frequency of beta-tubulin mutations in Japanese patients with small and non-small cell lung cancer, direct sequence analysis following reverse transcription-polymerase chain reaction (RT-PCR) of the beta-tubulin gene was performed using total RNA from 20 lung cancer cell lines and 22 specimens from lung cancer patients. First-strand cDNA sequence analysis of the 42 samples showed silent mutations at codon 180 of the beta-tubulin gene, which encodes the GTP-binding site of the protein, and codons 195 and 217. However, neither missense nor non-sense mutations affecting microtubule dynamics, within or near the GTP-binding site of the beta-tubulin gene, were detected. These results indicate that beta-tubulin gene mutations might not play a major role in the mechanism of resistance to paclitaxel in Japanese lung cancer patients. Further investigations are needed to clarify the mechanism of drug resistance.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Small Cell/genetics , Lung Neoplasms/genetics , Mutation/genetics , Tubulin/genetics , Tumor Cells, Cultured/physiology , Biopsy , DNA Mutational Analysis , DNA Primers/chemistry , DNA, Neoplasm/metabolism , Humans , Lung Neoplasms/mortality , Polymerase Chain Reaction , RNA, Messenger/metabolism , RNA, Neoplasm/metabolism
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