Reiko Yoshino

Phase II study of oral S-1 and cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer

PURPOSE To determine the efficacy and safety of oral S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS S-1 (50mg/m(2)) was administered orally twice daily for 14 days, with cisplatin (40 mg/m(2)) on days 1 and 8 of each cycle every 3 weeks, for 2-4 cycles. Thoracic radiation therapy was administered in 2 Gy fractions five times weekly for a total dose of 60 Gy. The primary endpoint was the response rate, and secondary endpoints included progression-free survival, overall survival and safety. RESULTS Forty-one patients were enrolled in this study. The objective response rate was 87.8% (98% CI: 77.8-97.8%). The median progression-free survival was 467 days (15.4 months), and the median survival time was 904 days (29.7 months). The overall survival rates at 1- and 2-years were 85.7% and 52.9%, respectively. Hematological toxicities included grade 3/4 neutropenia (17%) and grade 3/4 leukopenia (27%). No grade 3 febrile neutropenia was detected, and grade 3/4 non-hematological toxicities were also mild. A grade 3 gastrointestinal hemorrhage was observed in one patient. CONCLUSIONS The combination of oral S-1 plus cisplatin with concurrent radiotherapy is a promising treatment with a high efficacy and lower toxicity in patients with locally advanced NSCLC.

Phase II study of oral S-1 plus cisplatin with bevacizumab for advanced non-squamous non-small cell lung cancer

BACKGROUND We conducted a phase II study to evaluate the efficacy and safety of S-1 plus cisplatin with bevacizumab followed by maintenance bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Chemotherapy-naïve patients received S-1 plus cisplatin with bevacizumab. S-1 (80 mg/m(2)) was administered orally twice daily for 14 days, cisplatin (60 mg/m(2)) on day 1, and bevacizumab (15 mg/kg) on day 1 and every 3 weeks for 4-6 cycles. Patients with an objective response or stable disease received maintenance bevacizumab every 3 weeks until disease progression. RESULTS Thirty patients were enrolled in this study. The median number of chemotherapy was four (range, 1-6 cycles), and the median number of bevacizumab alone was three (range, 1-31 cycles). The grade 3/4 toxicities were neutropaenia (23%), thrombocytopaenia (10%), febrile neutropaenia (3%), hypertension (17%), pneumonia (7%), and bowel perforation (3%). The objective response rate was 71% (95% CI, 55-88%) for a disease control rate of 100%. The median progression-free and overall survival times were 7.0 months and 20.0 months, respectively. CONCLUSIONS S-1 plus cisplatin with bevacizumab is an active and well-tolerated regimen in patients with chemotherapy-naïve non-squamous NSCLC.

Clinical impact of postprogression survival for overall survival in elderly patients (aged 75 years or older) with advanced nonsmall cell lung cancer.

INTRODUCTION The effects of first-line single-agent chemotherapy on overall survival (OS) might be confounded by subsequent treatments in elderly patients with nonsmall cell lung cancer (NSCLC). We, therefore, aimed to evaluate whether progression-free survival (PFS), postprogression survival (PPS), or tumor response might be a valid surrogate endpoint for OS in this patient population. PATIENTS AND METHODS We retrospectively reviewed the clinical data of 58 elderly patients with advanced NSCLC, who received first-line single-agent cytotoxic chemotherapy at our institution between October 2003 and November 2013. The relationships of PFS, PPS, and tumor response with OS were individually analyzed. RESULTS The study cohort included 46 men and 12 women with a median age of 79 years (range: 75-87 years). There were 30 adenocarcinomas, 22 squamous cell carcinomas, and 6 other histologic types with 1 stage IIIA, 9 IIIB, and 48 IV cases. The performance status (PS) scores were 0, 1, and 2 in 18, 35, and 5 patients, respectively. The median PFS and OS were 2.8 and 5.4 months, respectively. Our analyses revealed a strong correlation of PPS and PFS with OS, whereas that between tumor shrinkage and OS was weak. Tumor stage and PS after initial treatment were significantly associated with PPS. Individual analysis indicated that PPS might serve as a surrogate for OS in elderly patients with advanced NSCLC receiving first-line single-agent chemotherapy. CONCLUSION Our findings suggested that the disease course after progression following first-line single-agent chemotherapy might influence the OS of elderly patients with advanced NSCLC.

Comparison of platinum combination re-challenge therapy and docetaxel monotherapy in non-small cell lung cancer patients previously treated with platinum-based chemoradiotherapy.

Platinum-based chemoradiotherapy (CRT) is a standard front-line treatment for locally advanced non-small cell lung cancer (NSCLC). However, no clinical trials have compared the efficacy and toxicity of platinum combination and docetaxel as subsequent re-challenge chemotherapies after cancer recurrence following CRT. This study aimed to evaluate the efficacy and toxicity of platinum combination chemotherapy versus docetaxel monotherapy in NSCLC patients previously treated with platinum-based CRT.From September 2002 to December 2009, at three participating institutions, 24 patients with locally advanced NSCLC, who had previously received platinum-based CRT, were treated with platinum combination re-challenge therapy, whereas 61 received docetaxel monotherapy. We reviewed their medical charts to evaluate patient characteristics and data regarding treatment response, survival, and toxicity.The response rates were 16.7% and 6.6% in the platinum combination chemotherapy and docetaxel monotherapy groups, respectively (p = 0.09), whereas disease control rates were 58.3% and 57.4%, respectively (p = 0.82). Progression-free survival was similar between the two groups (median, 4.2 vs. 2.3 months; hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.51–1.29; p = 0.38), as was overall survival (median, 16.5 vs. 13.0 months; HR = 0.82; 95% CI = 0.47–1.41; p = 0.47). The incidence and severity of toxicity was also similar between the two groups. Hematological toxicity, particularly leukopenia and neutropenia, was more frequent in the docetaxel group.Our results indicated that platinum combination re-challenge was equivalent to docetaxel for relapsed patients previously treated with platinum-based CRT.

P2-13-3COMPARISON OF THE RADIOTHERAPEUTIC EFFICACY IN NSCLC WITH POSTOPERATIVE MEDIASTINAL LYMPH NODES RECURRENCE AND STAGE III

Abstract Background: Whether local treatment would be equally effective in non-small cell lung cancer patients with postoperative mediastinal lymph nodes recurrence (group A) and primary stage III disease (group B) remains unclear. Methods: Between 2002 and 2009, in a total of 190 non-small cell lung cancer patients with mediastinal lymph nodes metastases treated by radiotherapy alone or chemoradiotherapy, the baseline patient characteristics, responses to radiotherapy alone or chemoradiotherapy and survival were compared between group A (n = 33) and group B (n = 157). Results: Male was the predominant gender, accounting for 60.6% of patients in group A and 78.9% of patients in group B (P = 0.04). Performance status (PS) 0 was the predominant PS, accounting for 78.7% of patients in group A and 57.3% of patients in group B (P = 0.02). The response rates in group A and group B were 66.6 and 72.3%, respectively (P = 0.64). PFS was not significant in group A and group B (median, 15.0 versus 11.0 months; hazard ratio, 0.78; 95% CI, 0.51–1.20; P = 0.26). Meanwhile, OS was superior in group A than in group B (median, 67.0 versus 39.0 months; hazard ratio, 0.56; 95% CI, 0.29–0.97; P = 0.03). Among postoperative patients, PFS (median, 12.5 versus 19.0 months; hazard ratio, 1.50; 95% CI, 0.64–3.49; P = 0.34) and OS (median, 67.0 versus 60.0 months; hazard ratio, 1.22; 95% CI, 0.36–4.14; P = 0.74) were no significance in radiotherapy alone group and chemoradiotherapy group, respectively. Conclusions: Postoperative mediastinal lymph nodes recurrent non-small cell lung cancer showed distinctive features: OS was superior in patients with postoperative mediastinal lymph nodes recurrence than in those with primary stage III disease, although the two groups showed comparable responses and PFS.

P3–120RETROSPECTIVE ANALYSIS OF RE-CHALLENGE OF EGFR TK-IS IN PATIENTS WITH ADVANCED AND RECURRENT NON-SMALL CELL LUNG CANCER

Background: The efficacy of re-administration of gefitinib was reported in the cases of response to initial treatment with gefitinib. We retrospectively evaluated the efficacy and safety of treatment with EGFR TK-Is re-challenge in patients with advanced and recurrent NSCLC in our institute. Methods and Result: Forty-four patients with advanced and recurrent NSCLC received EGFR TK-Is re-challenge from October 2003 to February 2013 in our institute. Twenty-four patients were treated with erlotinib after failure of the initial gefitinib treatment. Male/female = 9/15; Median age was 69 years; smoker/ non-smoker = 7/17; ECOG PS 0/1/2/3 = 17/3/3/1. Response rate(RR) was 30.4% and disease control rate (DCR) was 73.9%. Grade3 rash (4.2%) and grade3 fatigue (4.2%) were observed. Dose reduction was needed in seven patients. Seventeen patients were re-treated with gefitinib after failure of the initial gefitinib treatment. Male/female = 2/ 15; Median age was 67 years; smoker/non-smoker = 3/14; ECOG PS 0/1/2/3 = 6/9/2/0. Response rate(RR) was 21.4% and disease control rate (DCR) was 85.7%. Grade3 interstitial lung disease (5.9%) and grade3 rush (5.9%) were observed. Dose reduction was needed in three patients. Three patients were re-treated with erlotinib after failure of the initial erlotinib treatment. Male/female = 2/1; smoker/non-smoker = 2/1; ECOG PS 0/1/2/3 = 0/3/0/0; CR/PR/SD/PD = 0/0/1/2. Dose reduction was needed in one patient. Conclusion: Treatment with EGFR TK-Is re-challenge is effective and well-tolerated.