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N. Seki



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    P3.10 - Poster Session 3 - Chemotherapy (ID 210)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
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      P3.10-012 - Feasibility study of docetaxel and bevacizumab in elderly patients with advanced nonsquamous non-small cell lung cancer: Thoracic Oncology Research Group (TORG) 1014. (ID 1148)

      09:30 - 09:30  |  Author(s): N. Seki

      • Abstract

      Background
      A series of Japanese trials indicate docetaxel (DTX) monotherapy is a standard of care in elderly patients with advanced non-small cell lung cancer (NSCLC), and that the addition of platinum does not significantly improve the outcomes. Bevacizumab (BEV) has been shown to be beneficial when added to standard platinum-doublet chemotherapy in good-risk NSCLC patients. BEV toxicity is a major concern for elderly patients.

      Methods
      Patients with chemotherapy-naïve advanced non-squamous NSCLC who were >70 year old with performance status (PS) 0/1 and adequate organ function were enrolled. Eligible patients received DTX 60 (Level 0) or 50 (Level -1) mg/m2 and BEV 15 mg/kg on day 1, every 3 weeks. Toxicity was the primary endpoint and secondary endpoints were response rate, progression free survival (PFS), overall survival (OS), and completion rate of the 3 cycles of treatment. The planned sample size was 12 to 24, with at least 6 subjects treated at each level.

      Results
      Between December 2010 and September 2012, 21 elderly patients (9 in level 0 and 12 in level -1) were enrolled in the study (median age, 75 years; 43% male; 90% adenocarcinoma; 67% PS 1). Two of the 9 patients in level 0 had a dose limiting toxicities (DLTs). After 9 patients enrolled on level 0, two severe adverse events were reported. One patient had grade 4 sepsis in cycle 4 and another patient had grade 4 sepsis in cycle 5. We decided to stop enrollment to level 0 and reduce dose to level -1. Two of 12 patients in dose level -1 experienced DLTs. Grade 3 or 4 of toxicities among all patients were neutropenia (86%), anemia (5%), hypertension (19%), anorexia (10%), and increased aminotransferase levels (10%). Three out of 9 patients in level 0 achieved partial response (PR) and 3 out of 11 assessable patients in level -1 obtained PR. Completion rates of the 3 cycles of treatment were 78% (7/9) in level 0 and 67 % (8/12) in level -1. The median PFS and OS were 5.4 and 11.1 months, respectively.

      Conclusion
      The recommended dose for this combination in future study is docetaxel 50 mg/m2 and bevacizumab 15mg/kg.

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      P3.10-016 - A phase I/II study of combination chemotherapy with erlotinib and S-1 in pretreated Non-Small Cell Lung Cancer (NSCLC): Thoracic Oncology Research Group (TORG) 0808/0913 (ID 1351)

      09:30 - 09:30  |  Author(s): N. Seki

      • Abstract

      Background
      In BR.21 Study, erlotinib was shown to significantly prolong OS, PFS and the time to progression of NSCLC-associated symptoms. The study reported that the RR was 7% for EGFR-wt cases but the MST was longer than placebo. S-1 is a fourth-generation oral fluoropyrimidine that contains tegafur, a prodrug of 5-fluorouracil (5-FU). The consecutive administration of S-1 at 80 mg/m[2]/day was well tolerated. The objective RR and MST were 22.0% and 10.2 months. Regarding the EGFR-TKI and 5-FU-based chemotherapy, EGFR-TKI has been shown in basic studies to reduce the expression of thymidilate synthase, the target enzyme for the 5-FU-based chemotherapy, at the protein and mRNA levels, and synergistic effects of gefitinib used in combination with S-1 have been reported in basic study. Thus, we conducted a phase I study to find the maximum tolerated doses of erlotinib/ S-1 combination therapy, and a phase II study to evaluate the efficacy and toxicity of this combination strategy as a 2nd/3rd-line therapy for recurrent/advanced NSCLC in the absence of EGFR gene mutations.

      Methods
      Eligibility criterias were as follows: 1) patients with histologically or cytologically diagnosed NSCLC, 2) patients at clinical stage IIIB or IV not indicated for radical radiotherapy/radical surgery or those with postoperative recurrence, 3) patients having received 2 or fewer prior regimens of chemotherapy (at least one regimen being platinum-based), 4) patients with no history of treatment with EGFR-TKI and drugs of the fluoropyridimine family. This combination chemotherapy consisted of two 3-week cycles of S-1 treatment and once daily erlotinib at a dose of 150 mg/body. In phase I study, the initial dose of S-1 was 60 mg/m[2]/day, and 3 patients were registered for each level of S-1 treatment. In phase II study, S-1 at recommended dose and erlotinib were administered similarly to the phase I study.

      Results
      In phase I study, seven patients (one man and 6 women) with a median age of 66 years (range: 52-70 years) were enrolled. All patients had ECOG PS of 0-1, six patients had adenocarcinomas, and one had large cell carcinoma. All patients were at clinical stage IV. No patient had grade 2 or more neutropenia, and each 1 had grade 2 leukocytepenia, anemia, mucositis, general fatigue, skin rash, and diarrhea; however, none experienced DLT. The RD for the phase II study was determined as 80 mg/m[2] S-1 and 150 mg/m[2] erlotinib. The phase II study was conducted in 10 patients, 9 men and 1 woman, with a median age of 60.5 years (range 42–75). PS was 0 in 2, 1 in 6, and 2 in 2 patients. The histological subtype was adenocarcinoma in 5 patients, squamous-cell carcinoma in 4, and others in 1. One patient had grade 3 diarrhea, grade 4 colitis, and grade 4 septic shock, and the other had grade 4 dehydration and acute respiratory failure which resulted in two treatment-related deaths. With these findings, the trial was closed to additional enrollment.

      Conclusion
      Erlotinib(150mg) and S-1(80 mg/m[2] for 14 days every 21 days) therapy seemed to be toxic for pretreated patients with EGFR-wt NSCLC patients.

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    P3.24 - Poster Session 3 - Supportive Care (ID 160)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P3.24-014 - Multicenter study of zoledronic acid in lung cancer patients with bone metastasis. Thoracic Oncology Research Group (TORG) 1017. (ID 1043)

      09:30 - 09:30  |  Author(s): N. Seki

      • Abstract

      Background
      Bone is the most frequent site of metastasis for lung cancer, and metastatic bone disease causes pain. Furthermore, bone metastasis may produce skeletal-related events (SREs) that greatly reduce quality of life and may even lead to death. Several guidelines have recommended use of bone-modifying agents (BMA) such as zoledronic acid (ZA) at the first diagnosis of bone metastases in patients with solid tumors, continued every 3-4 weeks as long as the patient is able to tolerate therapy or until evidence of a substantial decline in performance status. However, due to the risk of osteonecrosis of the jaw (ONJ) and a perceived lack of evidence for reduced SRE in lung cancer, some physicians have hesitated to administer ZA in lung cancer patients with bone metastasis. Therefore, the main objective of the present study was both to describe real world data of ZA and to compare SREs among previous reports.

      Methods
      All patients with non-small cell lung cancer (NSCLC) accompanied by metastatic bone disease (MBD) who were administered ZA at least twice from 12 hospitals in the TORG in Japan between January 2008 and December 2009 were eligible for inclusion in the study.

      Results
      A total of 198 consecutive patients (126 men, 72 women; median age, 64 years; range, 44-89 years) were identified. Histological type was as follows: adenocarcinoma (n=131, 66%); squamous cell carcinoma (n=30, 15%); and others (n=37, 19%). About two-thirds of patients experienced SRE before starting anti-cancer therapy. Median duration of ZA administration was 106 days (range, 28-1126 days), and median number of ZA administrations was four (range, 2-41). Median time to first SRE in patients who experienced SRE after treatment was 202 days (range, 156-264 days). No ONJ was reported from the 198 patients.

      Conclusion
      We found that ZA was not used sufficiently in clinical practice in Japan. Our data suggest that ONJ during the treatment of lung cancer patients is very rare, and ZA is potentially useful in lung patients with bone metastasis.