Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105.

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.

[Twenty-one patients of malignant pleural mesothelioma in the Senshu district].

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.

Phase I dose-escalation and pharmacokinetic trial of lapatinib (GW572016), a selective oral dual inhibitor of ErbB-1 and -2 tyrosine kinases, in Japanese patients with solid tumors.

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.

Large cell neuroendocrine carcinoma of the mediastinum with alpha-fetoprotein production.

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.

Phase I and pharmacokinetic study of combination chemotherapy using irinotecan and paclitaxel in patients with lung cancer.

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.

Pulmonary lymphoma of mucosa-associated lymphoid tissue type followed as a long-standing indeterminate lesion in immunoglobulin M-type paraproteinemia.

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.

A phase I study of irinotecan in combination with amrubicin for advanced lung cancer patients.

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.

Randomized phase II study of carboplatin/gemcitabine versus vinorelbine/gemcitabine in patients with advanced nonsmall cell lung cancer: West Japan Thoracic Oncology Group (WJTOG) 0104.

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.

Retrospective analysis of the predictive factors associated with the response and survival benefit of gefitinib in patients with advanced non-small-cell lung cancer.

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.

Phase II study of irinotecan and carboplatin for advanced non-small cell lung cancer.

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.

Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan.

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.

Mutational analysis of the beta-tubulin gene in lung cancer.

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.