Author of

• 10743

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  P1.10 - Poster Session 1 - Chemotherapy (ID 204)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/28/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 10788

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    P1.10-045 - Validation Study of Postoperative Platinum-based Adjuvant Chemotherapy for Japanese Patients with Completely Resected Pathological StageIIIA Non-small Cell Lung Cancer (ID 2608)

    09:30 - 09:30  |  Author(s): N. Masuda
    • Abstract

    Background
    In the Japanese Clinical Practice Guideline for Lung Cancer, postoperative platinum-based adjuvant chemotherapy in patients with pathological stage IIIA (p-stage IIIA) non-small cell lung cancer (NSCLC) is recommended (grade B). However, the verification of the effect of adjuvant chemotherapy in Japanese patients is not sufficient. In this study, we aimed to validate the effectiveness of platinum-based adjuvant chemotherapy for p-stage IIIA NCSLC.

    Methods
    Between January 2002 and December 2009, we retrospectively reviewed records of patients with completely resected p-stage IIIA NSCLC in our institution. Exclusion criteria include the patients with oral anticancer drug, tegafur and uracil (UFT), >75 years old, large cell neuroendocrine carcinoma and pleomorphic carcinoma. The primary endpoint of this study was progression-free survival. Cumulative survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test. Multivariable analysis was performed with the Cox proportional hazards regression model to estimate the independent prognostic effect of adjuvant chemotherapy on prognosis by adjusting for confounding factors.

    Results
    Sixty-seven patients (median age, 63 years; 40 men, 27 women) were eligible. 49 patients had adenocarcinoma and 18 had squamous cell carcinoma. 63 patients underwent lobectomy and 4 patients had pneumonectomy. Of the 33 patients with platinum-based adjuvant chemotherapy regimens, 16 had cisplatin plus gemcitabine, 13had carboplatin plus paclitaxel, and 4 had cisplatin plus vinorelbine. Five-year progression-free survival (PFS) and 5-year overall survival (OS) in the adjuvant chemotherapy group versus in surgery alone group were not statistically significant (5-year PFS rates were 28% and 31%, respectively; p = 0.69, and 5-year OS rates were 54% and 40%, respectively; p = 0.10). Multivariate analysis showed that platinum-based adjuvant chemotherapy did not affect patient prognosis significantly (HR, 0.70; 95% CI, 0.37-1.32; p=0.27).

    Conclusion
    Our date showed that platinum-based adjuvant chemotherapy in patients with p-stage IIIA NSCLC did not have such impact on our patient’s prognosis as we could understand in daily medical practice. Although there were some limitations of this study, we feel a strong need for searching more effective chemotherapy regimens or individualized treatment strategies.

• 11692

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  P2.10 - Poster Session 2 - Chemotherapy (ID 207)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11704

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    P2.10-012 - Evaluation of Amrubicin as a Third or Later Line of Chemotherapy for Advanced Non-Small Cell Lung Cancer (ID 943)

    09:30 - 09:30  |  Author(s): N. Masuda
    • Abstract

    Background
    Currently, there are no standard cytotoxic treatments for non-small-cell lung cancer (NSCLC) patients beyond third-line or further line therapy. Previous studies of amrubicin in patients with previously untreated advanced NSCLC in succession demonstrated an overall response rate of 18.3-27.9%, and a median survival time of 8.2-9.8 months. Accordingly, amrubicin was equivalent to anticancer agents such as taxanes, gemcitabine, vinorelbine, and pemetrexed in terms of single-agent activity against NSCLC. The purpose of this study was to evaluate the efficacy of amrubicin monotherapy as a salvage treatment in heavily pretreated NSCLC patients.

    Methods
    The records of NSCLC patients who received amrubicin monotherapy as a third or later line of chemotherapy at a Kitasato University Hospital between January 2009 and December 2012 were retrospectively reviewed. Amrubicin was administered to patients by intravenous injection in a dose of 35 mg/m[2] or 40 mg/m[2] daily on 3 consecutive days, and cycles were repeated at 3-week intervals.

    Results
    There were 36 patients who met the inclusion criteria. Their median number of prior chemotherapy was 4 (range: 2 to 7), and the median number of cycles of chemotherapy per patient was 4 (range: 1 to 9). Grade 3 or 4 hematologic toxicities included neutropenia (61.1%), leukopenia (58.3%), thrombocytopenia (22.2%), and anemia (11.1%). Febrile neutropenia occurred in 8 patients (22.2%). Non-hematologic toxicities were mild. Treatment related death was not observed. The overall response rate, median progression-free survival time, and median survival time were 8.3%, 1.7 months, and 6.3 months, respectively. Progression-free survival time was the same, 1.7 months, in both the 35 mg/m[2] dose group and the 40 mg/m[2] dose group.Figure 1Figure 2

    Conclusion
    Amrubicin exhibits modest activity and acceptable toxicity when used as a third or later line of chemotherapy for advanced NSCLC.

• 12592

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

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12612

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    P3.10-020 - Phase I and Pharmacokinetic Study of Erlotinib Administered in Combination With Amrubicin in Patients With Previously Treated, Advanced Non-Small Cell Lung Cancer (ID 1403)

    09:30 - 09:30  |  Author(s): N. Masuda
    • Abstract

    Background
    Standard second-line chemotherapy against advanced non-small-cell lung cancer (NSCLC) is a single agent such as docetaxel, pemetrexed, or erlotinib. The response rate of each agent as second-line setting are from 10% to 15% in Japanese NSCLC without EGFR mutation. Amrubicin, a totally synthetic 9-aminoanthracycline, is active as second-line chemotherapy for advanced NSCLC. The reported response rate to amrubicin as second-line treatment for advanced NSCLC is 11.5%. Erlotinib is an orally active reversible inhibitor of epidermal growth factor receptor tyrosine kinase activity (EGFR-TKI), which induces rapid tumor shrinkage if the tumor harbors EGFR activated mutation. Erlotinib is also effective for NSCLC without EGFR mutation, but the response rate is around 8%. We considered it worthwhile to explore if a doublet regimen consisting of amrubicin and erlotinib may provide therapeutic benefit and have a favorable toxicity profile. We performed the growth inhibition assay for NSCLC cell lines and made two-dimension isobolograms to estimate the synergy of the combination. The combination of amrubicin and erlotinib had significant synergistic effect on EGFR wild type NSCLC cell line A549, and additive effect on EGFR mutant cell line PC-9. We conducted a phase I trial of this combination. The aim was to determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs) and pharmacokinetics of this combination in patients with non-small cell lung cancer (NSCLC) who had previous chemotherapy.

    Methods
    Nine patients with stage IV disease were treated at 3-week intervals with erlotinib once daily on days 1-21 plus amrubicin 5-min intravenous injection on days 1-3.

    Results
    The dose levels evaluated were erlotinib (mg/day)/amrubicin (mg/m[2]): 100/30 (n = 3), 100/35 (n = 3) and 150/30 (n = 3). The MTD of erlotinib and amrubicin was 100 mg/day and 35 mg/m[2] since two of the three patients experienced DLTs during the first cycle of treatment at the third dose level of 150 mg/day and 30 mg/m[2]. Cessation of erlotinib administration for 8 days due to grade 3 leukopenia and grade 3 skin infection (erysipelas) were the DLTs. No drug-drug interactions between erlotinib and amrubicin were observed in this study. The overall response rate was 33%, including three partial responses, in the nine patients. The median progression-free survival for all patients was extraordinary long 11.3 months, and the median overall survival has not yet been reached.

    Conclusion
    Combined erlotinib plus amrubicin therapy seems to be highly effective, with acceptable toxicity, against NSCLC. The recommended dose for phase II studies was erlotinib 100 mg once daily on days 1-21, and amrubicin 35 mg/m[2] on days 1-3 administered every 21 days.

• 12853

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

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Supportive Care
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12867

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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. Masuda
    • 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.