Phase III study of adjuvant gemcitabine compared with adjuvant uracil-tegafur in patients with completely resected pathological stage IB-IIIA non-small cell lung cancer (WJTOG0101).

Background: Adjuvant oral uracil-tegafur (UFT) has led to significantly longer postoperative survival among patients with non-small-cell lung cancer (NSCLC). Gemcitabine (GEM) monotherapy is also reportedly effective for NSCLC and has minor adverse events (AEs). This study compared the efficacy of GEM- versus UFT-based adjuvant regimens in patients with completely resected pathological stage (p-stage) IB-IIIA NSCLC.

Efficacy and safety of transbronchial microwave ablation therapy under moderate sedation in malignant central airway obstruction patients with respiratory failure: a single-institution retrospective study.

Background: The safety and efficacy of transbronchial microwave ablation (TMA) therapy in patients with malignant central airway obstruction (CAO) with respiratory failure remains unclear.

Methods: A total of 38 patients with advanced non-small cell lung cancer (NSCLC) or lung metastases with malignant endoluminal obstruction received TMA therapy under moderate sedation and high fractions of inspired oxygen (FiO). The success rate of airway patency restoration, complication rate, and overall survival time (OS) from the initiation of TMA therapy were compared in the following two groups of patients with malignant CAO patients: the group with respiratory failure (PaO/FiO ≤ 300) (RF group, n = 10) and the group without respiratory failure (PaO/FiO > 300) (non-RF group, n = 28) at the time of the TMA therapy.

Phase II study of vinorelbine plus carboplatin with concurrent radiotherapy in elderly patients with non-small cell lung cancer.

Objective: Concurrent chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer. In the current aging society, the establishment of an ideal treatment strategy for locally advanced non-small cell lung cancer in the elderly is warranted. To assess the efficacy of concurrent chemoradiotherapy with carboplatin and vinorelbine in elderly patients with locally advanced non-small cell lung cancer.

Additional bevacizumab in EGFR-mutant lung adenocarcinoma patients who had oligo-progression after the failure of EGFR-TKI: A single-institute retrospective study.

Introduction: In EGFR-mutant NSCLC patients with oligo-progression disease (oligo-PD) after the EGFR-TKI failure, additional local ablative therapy (LAT) including stereotactic ablative radiotherapy reportedly extends the duration of the current EGFR-TKI and prolongs survival times. In clinical practice, however, all the patients cannot receive LAT for oligo-PD.

Methods: We retrospectively evaluated the efficacy and tolerability of additional bevacizumab as an alternative to LAT for oligo-PD after the EGFR-TKI failure in previously treated lung adenocarcinoma patients (median number of previous therapies, 2 regimens).

Toxicity and Efficacy of Sequential Chemotherapy in Patients with p-stage I Non-small Cell Lung Cancer that Recurring during Postoperative Tegafur-Uracil Adjuvant Chemotherapy.

It is not clear whether sequential chemotherapy can be performed immediately in patients with p-stage I non-small cell lung cancer recurring during a 2-year period of daily oral administration with tegafur-uracil (UFT) as postoperative adjuvant chemotherapy. Patients receiving chemotherapy within 1 month after the discontinuation of UFT (n = 10) (five cases with aggressive recurrent tumors) had the increased risk of grade 4 neutropenia, but the overall survival was not inferior to that in patients who received chemotherapy beginning more than 1 month (n = 11). We could perform sequential chemotherapy immediately while paying attention to grade 4 neutropenia.

Re-administration of Chemotherapy in Patients with Advanced Non-small Cell Lung Cancer Who Recovered from Chemotherapy-induced Interstitial Lung Disease.

We reported that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor re-administration (TKI-R) might be salvage therapy in patients with advanced non-small cell lung cancer after recovery from EGFR-TKI-induced interstitial lung disease (ILD). Here we retrospectively evaluated whether chemotherapy re-administration (CT-R) was effective in patients after chemotherapy-induced ILD. After providing their informed consent due to the risk of severe ILD, five patients received CT-R and six received TKI-R with oral administration of 0.

Population Pharmacokinetics and Adverse Events of Erlotinib in Japanese Patients with Non-small-cell Lung Cancer: Impact of Genetic Polymorphisms in Metabolizing Enzymes and Transporters.

Determinants of interindividual variability in erlotinib pharmacokinetics (PK) and adverse events remain to be elucidated. This study with 50 Japanese non-small-cell lung cancer patients treated with oral erlotinib at a standard dose of 150 mg aimed to investigate whether genetic polymorphisms affect erlotinib PK and adverse events. Single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP1A1, CYP1A2, CYP2D6, CYP3A4, CYP3A5, UGT1A1, UGT2B7, GSTM1, and GSTT1) or efflux transporters (ABCB1, and ABCG2) were analyzed as covariates in a population PK model.

Outcome in advanced non-small cell lung cancer patients with successful rechallenge after recovery from epidermal growth factor receptor tyrosine kinase inhibitor-induced interstitial lung disease.

Purpose: Several non-small cell lung cancer (NSCLC) cases of successful rechallenge with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) after recovery from gefitinib or erlotinib-induced interstitial lung disease (ILD) have been reported, but it is not clear whether the rechallenge affects the outcome.

Methods: We retrospectively evaluated the difference in the outcome between advanced NCLC patients with active EGFR mutations who received EGFR-TKI rechallenge after recovery from EGFR-TKI-induced ILD and those who did not.

Results: EGFR-TKI-induced ILD occurred in 11 (10%) of 110 patients receiving gefitinib, five (7%) of 73 patients receiving erlotinib and one (8%) of 13 patients receiving afatinib.

Tolerability and efficacy of afatinib at a low starting dosage in 10 elderly or low performance status patients with advanced refractory non-small-cell lung cancer.

Background: Whether a full dosage of afatinib is tolerable and effective for elderly or low performance status (PS) patients with advanced refractory non-small-cell lung cancer (NSCLC) is unclear.

Methods: We retrospectively evaluated the tolerability and efficacy of afatinib in 10 patients (the majority elderly) with a low PS score (2 or 3), who had advanced refractory adenocarcinoma and were carrying active epidermal growth factor receptor mutations. Afatinib was administered at a starting dosage of 20 or 30mg/day, followed by 10mg increases in dose up to a maximum dosage of 40mg/day.

Phase I study of irinotecan for previously treated lung cancer patients with the UGT1A1*28 or *6 polymorphism: Results of the Lung Oncology Group in Kyushu (LOGIK1004A).

Background: Various polymorphisms have been detected in the UDP-glucuronosyltransferase 1A ( UGT1A ) gene, and UGT1A1 *28 and UGT1A1 *6 have important effects on the pharmacokinetics of irinotecan and the risk of severe toxicities during irinotecan therapy. This study was conducted to determine the maximum tolerated dose (MTD) of irinotecan chemotherapy according to the UGT1A1 genotype in previously treated lung cancer patients with the UGT1A1 *28 or UGT1A1 *6 polymorphism.

Methods: The eligibility criteria were as follows: lung cancer patients that had previously been treated with anticancer agents other than irinotecan, possessed the UGT1A1 *28 or UGT1A1 *6 polymorphism (group A included *28/*28, *6/*6, and *28/*6, and group B included *28 /- and *6 /-), were aged ≤75 years old, had a performance score of 0-1, and exhibited adequate bone marrow function.

Phase II trial of weekly nab-paclitaxel for previously treated advanced non-small cell lung cancer: Kumamoto thoracic oncology study group (KTOSG) trial 1301.

Objectives: We performed an open-label, multicenter, single-arm phase II study (UMIN ID 000010532) to prospectively evaluate the efficacy and safety of nab-paclitaxel for previously treated patients with advanced non-small cell lung cancer (NSCLC).

Methods: Patients with advanced NSCLC who experienced failure of prior platinum-doublet chemotherapy received weekly nab-paclitaxel (100mg/m(2)) on days 1, 8, and 15 of a 21-day cycle until disease progression or the development of unacceptable toxicity. The primary end point of the study was objective response rate (ORR).

Preoperative Percutaneous Transthoracic Needle Biopsy Increased the Risk of Pleural Recurrence in Pathological Stage I Lung Cancer Patients With Sub-pleural Pure Solid Nodules.

We retrospectively evaluated whether preoperative percutaneous transthoracic needle biopsy (PTNB) affected the incidence of pleural recurrence in pathological stage I lung cancer patients. Pleural recurrence occurred in pure solid nodule (PSN) cases but not in ground-glass nodule cases, as evaluated using thin-section computed tomographic imaging. When the cases were restricted to sub-pleural PSN, the incidence of recurrence tended to be higher in a PTNB group (63 patients diagnosed by PTNB) than in a non-PTNB group (86 patients diagnosed by transbronchial biopsy or intraoperative diagnosis) (25% vs.

Prospective study of the UGT1A1*27 gene polymorphism during irinotecan therapy in patients with lung cancer: Results of Lung Oncology Group in Kyusyu (LOGIK1004B).

Background: Uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1*27) is known to impair the effect of UGT in basic research; however, little clinical investigation has been conducted. To evaluate the effect of the UGT1A1*27 polymorphism in irinotecan therapy, we conducted a prospective study.

Methods: Eligibility criteria included: lung cancer patients; scheduled irinotecan therapy doses of single ≥ 80, combination ≥ 50, radiation with single ≥ 50, or radiation with combination ≥ 40 mg/m(2); age ≥ 20; and Eastern Cooperative Oncology Group performance score (PS) 0-2.

The Ratio KL-6 to SLX in Serum for Prediction of the Occurrence of Drug-Induced Interstitial Lung Disease in Lung Cancer Patients with Idiopathic Interstitial Pneumonias Receiving Chemotherapy.

We retrospectively evaluated whether the ratio KL-6 to SLX in serum (K/S ratio) before chemotherapy was a predictor for the occurrence of drug-induced interstitial lung disease (D-ILD) in lung cancer patients with idiopathic interstitial pneumonias (IIPs). D-ILD occurred in 8 of 20 IIPs-positive cases and in 14 of 100 IIPs-negative cases (40 vs. 14%, p = .

Difference in benefit of chemotherapy between small cell lung cancer patients with interstitial pneumonia and patients with non-small cell lung cancer.

Background: It is not clear whether there is a difference in benefit of chemotherapy between small cell lung cancer (SCLC) patients with pre-existing idiopathic interstitial pneumonias (IIPs) and non-small cell lung cancer (NSCLC) patients with IIPs.

Patients And Methods: We performed a retrospective study of the overall survival (OS) between advanced lung cancer patients with IIPs (n=28) and those without IIPs (n=145).

Results: The OS in NSCLC patients with IIPs was shorter than in those without IIPs (median OS, 10.

Current status and future perspectives of cooperative study groups for lung cancer in Japan.

The performance of scientifically and ethically valid prospective clinical trials is the only means by which to obtain reliable clinical evidence that can improve clinical practice and thus the outcome of patients with lung cancer. The efficacy of treatment for advanced lung cancer remains limited; many cooperative study groups for lung cancer have been established in Japan since 1990s, and they have completed several landmark investigator-initiated clinical trials. This review highlights eight active Japanese cooperative study groups for lung cancer and summarizes their achievements made through clinical trials.

Complications associated with endobronchial ultrasound-guided transbronchial needle aspiration: a nationwide survey by the Japan Society for Respiratory Endoscopy.

Background: With the recent widespread use of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), there have been occasional reports on complications associated with its use. Previous reviews on EBUS-TBNA have been limited to studies by skilled operators, thus the results may not always be applicable to recent clinical practice. To assess the safety of EBUS-TBNA for the staging and diagnosis of lung cancer in Japan, a nationwide survey on its current usage status and complications associated with its use was conducted by the Japan Society for Respiratory Endoscopy (JSRE).

Association of ABCB1 polymorphisms with erlotinib pharmacokinetics and toxicity in Japanese patients with non-small-cell lung cancer.

Aims: We analyzed the association of ABCB1 polymorphisms with erlotinib-induced toxicity and the pharmacokinetics in patients with non-small-cell lung cancer.

Materials & Methods: After erlotinib 150 mg was administered to 50 patients, ABCB1 polymorphisms were analyzed via either TaqMan(®) assays or direct nucleotide sequencing. Plasma concentrations were measured by HPLC.

A phase II study of cisplatin and irinotecan as induction chemotherapy followed by concomitant thoracic radiotherapy with weekly low-dose irinotecan in unresectable, stage III, non-small cell lung cancer: JCOG 9706.

Objective: It is important to identify optimal regimens of cisplatin-based, third-generation chemotherapy and thoracic radiotherapy for patients with unresectable, Stage III, non-small cell lung cancer.

Methods: Patients with unresectable, Stage III non-small cell lung cancer were treated with the following regimen: cisplatin 80 mg/m(2) on days 1 and 29, with irinotecan 60 mg/m(2) on days 1, 8, 15, 29, 36, and 43 and 30 mg/m(2) on days 57, 64, 71, 78, 85 and 92. Thoracic radiotherapy was started on day 57 at 2 Gy/day (total 60 Gy).

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.

A phase II trial of gefitinib monotherapy in chemotherapy-naïve patients of 75 years or older with advanced non-small cell lung cancer.

Background: Gefitinib has shown modest activity in patients with recurrent non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. However, the activity of gefitinib as first-line chemotherapy remains unclear, especially unknown in elderly patients. A multicenter phase II trial was conducted to evaluate the efficacy and tolerability of gefitinib for elderly patients with chemotherapy-naïve NSCLC.

Tegafur-uracil plus gemcitabine combination chemotherapy in patients with advanced non-small cell lung cancer previously treated with platinum.

Background: An open-label, single-arm prospective study was conducted to evaluate the efficacy and toxicity of the combination of gemcitabine and tegafur-uracil (UFT) in patients with advanced nonsmall-cell lung cancer (NSCLC) after the failure of previous platinum-containing regimens.

Patients And Methods: Patients with advanced NSCLC received 200 mg/m2 of UFT twice daily from day 1 through 14 plus 900 mg/m2 of gemcitabine per day via intravenous injection on days 8 and 15. This regimen was repeated every 3 or 4 weeks.

[Clinical analysis of primary lung cancer with a thin-walled cavity to explain the mechanism of thin-walled cavity formation].

We report 8 rare cases of primary lung cancer which showed a thin-walled cavity on chest X-ray and CT. We analyzed 8 cases (7 men, 1 woman) of primary lung cancer with thin-walled cavities admitted to our hospital between 1995 and 2006. The subjects were aged between 45 and 84 years of age (median: 72 years old).

Catheter drainage followed by the instillation of bleomycin to manage malignant pericardial effusion in non-small cell lung cancer: a multi-institutional phase II trial.

Introduction: Malignant pericardial effusion (MPE) causes cardiac tamponade and an extremely poor outcome unless it is well controlled. The effect of pericardial drainage and the intra-pericardial instillation of bleomycin on the control of MPE was examined in this prospective multi-institutional phase II trial.

Methods: In eligible patients with cytologically defined MPE resulting from non-small cell lung cancer, the pericardial effusion of such cases was continuously drained.

Phase II study of 3-week scheduling of irinotecan in combination with cisplatin in patients with advanced nonsmall-cell lung cancer.

Objectives: The combination of irinotecan and cisplatin given every 4 weeks is one of the standard treatments for advanced nonsmall-cell lung cancer (NSCLC) in Japan. The purpose of this study is to evaluate the efficacy, safety and dose-intensity as a measure of the feasibility of 3-week scheduling of irinotecan and cisplatin in patients with advanced NSCLC in phase II study.

Methods: Previously untreated patients with stage IIIB and IV NSCLC were treated intravenously with irinotecan (60 mg/m2) on days 1 and 8 and cisplatin (60 mg/m2) on day 1 of a 3-week cycle.