Temiko Shimada

Combined Analysis of V20, VS5, Pulmonary Fibrosis Score on Baseline Computed Tomography, and Patient Age Improves Prediction of Severe Radiation Pneumonitis After Concurrent Chemoradiotherapy for Locally Advanced Non-Small-Cell Lung Cancer

Introduction: We aimed to develop a more accurate model for predicting severe radiation pneumonitis (RP) after concurrent chemoradiotherapy for non–small-cell lung cancer. Methods: We retrospectively analyzed data from 122 patients with locally advanced non–small-cell lung cancer treated with concurrent chemoradiotherapy. Several dose-volume histogram metrics including absolute lung volume spared from a 5 Gy dose (VS5) were analyzed for an association with RP above NCI-CTC grade 3 (RP ≥ G3). Clinical factors including pulmonary fibrosis score (PFS) and pulmonary emphysema score on baseline chest computed tomography (CT) were also analyzed. Results: Fourteen patients (11.4%) developed RP greater than or equal to G3. On univariate analysis, all dose-volume histogram metrics, sex, and PFS on baseline CT were significantly (p < 0.05) associated with occurrence of RP greater than or equal to G3. Multivariate analysis revealed that V20 greater than or equal to 26%, VS5 less than 1500 cc, age greater than or equal to 68 years, and PFS on baseline CT greater than or equal to 2 were significant risk factors. Thus, we defined a new predictive risk score (PRS) that combines these factors. The cumulative incidence of RP greater than or equal to G3 at 12 months were 0%, 7.8%, 26.6%, and 71.4% when the PRS was 0, 3–5, 6–8, and 9–14, respectively (p < 0.001). This PRS was superior at predicting RP than both V20 and VS5 combined, or V20 alone by receiver operating characteristic analysis (area under the curve, 0.888 versus 0.779 versus 0.678). Conclusions: V20, VS5, age, and PFS on baseline CT are independent and significant risk factors for occurrence of severe RP. Combining these factors may improve the predictability of severe RP.

Randomized Phase II Study of Two Different Schedules of Gemcitabine and Oral S-1 in Chemo-naïve Patients with Advanced Non-small Cell Lung Cancer

Introduction: This study was conducted to evaluate the efficacy and safety and to compare dosing schedules of gemcitabine combined with S-1 in chemo-naïve non-small cell lung cancer patients. Methods: Patients with chemo-naïve stage IIIB/IV non-small cell lung cancer were randomized into two treatment arms. Patients were given oral S-1 (60 mg/m2/d, twice a day) from days 1 to 14 with gemcitabine (1000 mg/m2/d) on days 1 and 8 (arm A) or on days 8 and 15 (arm B). This cycle was repeated every 21 days. Results: A total of 80 patients were entered in this trial. The primary end point of this study was response rate. The response rates of arm A and arm B were 22.0 and 28.9%, respectively (p = 0.606). Median time to treatment failure in arm A was 3.6 months and 4.8 months in arm B. Median time to progression in arm A was 4.1 months and 5.5 months in arm B. Median survival time in arm A and arm B was 15.5 months and 18.8 months, respectively. The toxicity profile was relatively mild and did not differ very much between two arms. Conclusion: The combination of gemcitabine and S-1 was determined to be feasible and effective for advanced non-small cell lung cancer. We selected arm B for further studies because of its higher response rate and survival data.

A phase 2 study of bevacizumab in combination with carboplatin and paclitaxel in patients with non-squamous non-small-cell lung cancer harboring mutations of epidermal growth factor receptor (EGFR) after failing first-line EGFR-tyrosine kinase inhibitors (HANSHIN Oncology Group 0109)

OBJECTIVES We have conducted a phase 2 study to evaluate the efficacy and safety of carboplatin, paclitaxel, and bevacizumab in patients with non-squamous non-small-cell lung cancer (NSCLC) who are epidermal growth factor receptor (EGFR) mutation positive and for whom EGFR-tyrosine kinase inhibitor (TKI) 1st-line has failed. MATERIALS AND METHODS Patients with stage IIIB or IV non-squamous NSCLC harbored activating EGFR mutations that has failed 1st-line EGFR-TKI and an Eastern Cooperative Oncology Group performance status of 0 or 1 were included in this study. Patients received carboplatin at an area under the concentration-time curve 5 or 6, paclitaxel 200mg/m(2), and bevacizumab 15mg/kg on D1. The combination therapy was repeated every 21 days for up to three to six cycles. Bevacizumab was continued until disease progression or unacceptable toxicity for patients without disease progression (PD). The primary endpoint was objective response rate (ORR). RESULTS Thirty-one patients were enrolled between March 2010 and January 2013, with 30 patients being eligible. ORR was 37% (90% CI; 24-52%) and disease control rate, 83% (95% CI; 66-92%). The median progression free survival (PFS) was 6.6 months (95% CI; 4.8-12.0 months) and median overall survival, 18.2 months (95% CI; 12.0-23.4 months). The most common grade ≥3 hematologic toxicity was neutropenia (93%), and non-hematologic toxicity, febrile neutropenia (20%). There were no clinically relevant grade ≥3 bleeding events and no treatment-related deaths. CONCLUSION The combination therapy of carboplatin, paclitaxel and bevacizumab did not achieve the initial treatment goal.

Phase 2 study of S‐1 and carboplatin plus bevacizumab followed by maintenance S‐1 and bevacizumab for chemotherapy‐naive patients with advanced nonsquamous non–small cell lung cancer

A previous phase 3 trial demonstrated noninferiority in terms of overall survival for combined S‐1 (an oral fluoropyrimidine) and carboplatin compared with combined paclitaxel and carboplatin as first‐line treatment for advanced non–small cell lung cancer (NSCLC). In the current study, the authors evaluated the efficacy and safety of combined S‐1, carboplatin, and bevacizumab followed by maintenance with S‐1 and bevacizumab in chemotherapy‐naive patients with advanced nonsquamous NSCLC.

Usefulness of the Oximetry Test for the Diagnosis of Sleep Apnea Syndrome in Japan

We evaluated the usefulness of oximetry tests that are frequently used as screening tools for sleep apnea syndrome (SAS) by determining the level of agreement between oximetry test results and polysomnography test (PSG) results. We retrospectively examined 135 patients suspected of having SAS. Although the oximetry desaturation index (DSI) seemed better than the oximetry apnea index in the agreement with the polysomnography respiratory disturbance index (RDI), the criteria of DSI greater than or equal to 15 was not sensitive enough to screen for moderate SAS (PSG-RDI ≥ 20). Multivariate analyses revealing that body mass index (BMI) as well as DSI correlated well with PSG-RDI, we established a new criterion by adding the BMI score (DSI ≥ 15 or BMI ≥ 25), which remarkably improved the sensitivity. This criterion may be useful not only in clinical practice but also in medical checkups for asymptomatic patients, and also suggests that obese patients with sleep disturbance should undergo PSGs, irrespective of the DSI score.

Concurrent chemoradiotherapy with cisplatin and S-1 or vinorelbine for patients with stage III unresectable non-small cell lung cancer: A retrospective study

BACKGROUND Concurrent chemoradiotherapy (CCRT) is the preferred treatment for stage III unresectable non-small cell lung cancer (NSCLC). However, there have been few reports on combination chemotherapy with radiation for second- and third-generation antitumor drugs, although clinical guidelines have recommended the use of these drugs along with platinum agents. METHODS We retrospectively analyzed the efficacy and toxicity of cisplatin and either S-1 or vinorelbine for treating stage III unresectable NSCLC patients who were treated with CCRT. RESULTS Between September 2006 and May 2014, 56 patients with unresectable stage III NSCLC were treated with CCRT with S-1 and cisplatin (median age: 63 years) and 58 patients were treated with CCRT with vinorelbine and cisplatin (median age: 61 years). The median follow-up time was 14.6 months in the S-1 arm and 28.0 months in the vinorelbine arm. We found no significant difference in progression-free survival (15.8 months vs. 10.1 months; p=0.15) and overall survival (33.7 months vs. 31.1 months; p=0.63) between the S-1 and vinorelbine arms, respectively. Severe (more than grade 3) leukopenia (35.7% vs. 98.2%; p<0.01), neutropenia (44.6% vs. 98.2%; p<0.01), and febrile neutropenia (1.8% vs. 46.6%, p<0.01) were significantly less frequent in the S-1 arm than in the vinorelbine arm. Treatment-related deaths were not observed in either arm. CONCLUSIONS CCRT with both S-1 or vinorelbine with cisplatin appears feasible based on their efficacy and toxicity profiles. Both treatments may be recommended as treatment options for patients with stage III unresectable NSCLC.

Prolonged Survival of a Patient with Lung Cancer after Treatment with S-1, a New Oral Fluoropyrimidine Anticancer Drug

A 36-yr-old woman complaining of cough and body weight loss at a health checkup and referred to us after an abnormality was noted on the chest X-ray was diagnosed with clinical stage IV (cT2N3M1) non-small-cell lung cancer (adenocarcinoma). She received three courses of chemotherapy. The response to treatment was stable disease. She was subsequently enrolled in a clinical trial of S-1, a new oral fluoropyrimidine anticancer drug, and received a total of 22 courses of S-1 over a period of 2 yr 5 mo. At the end of treatment, she was classified as having a partial response. A bronchoscopic biopsy disclosed no cancer cells. Remission continued for 1 yr 7 mo after treatment. The patient died of primary disease 8 yr after the initiation of treatment with oral S-1. Non-small-cell lung cancer was approved as a new indication of S-1 in 2004 in Japan, but the number of patients receiving it for this indication remains limited. Here, we describe our experience with a patient with adenocarcinoma of the lung who survived for a prolonged period after treatment with S-1. Our findings suggest that S-1 is effective for the treatment of non-small-cell lung cancer.