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J. Sasaki



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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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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): J. Sasaki

      • 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.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 2
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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): J. Sasaki

      • 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.

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      P2.10-020 - Dose escalation and pharmacokinetic study of carboplatin and pemetrexed for elderly patients with advanced non-squamous, non-small-cell lung cancer: Kumamoto Thoracic Oncology Study Group Trial 1002 (ID 1329)

      09:30 - 09:30  |  Author(s): J. Sasaki

      • Abstract

      Background
      This study was designed to determine the recommended dose of carboplatin-pemetrexed in elderly(≧70 years old), chemotherapy-naïve patients with advanced non-squamous non-small-cell lung cancer. Also, we measured the blood level of pemetrexed in order to explore significant factors associated with toxicity or efficacy.

      Methods
      The patients were treated with carboplatin and pemetrexed every three weeks from 4 to 8 cycles. The dose of the anticancer drug escalated according to protocol.

      Results
      Grade 3 infection was observed as DLT at a dose of carboplatin AUC 5 and pemetrexed 500 mg/m[2], and we determined this phase as a recommended dose. Overall response rate was 15.3%, and the disease control rate was 76.9% in all cases. The median duration of progression-free survival was 3.9 months. The AUC of pemetrexed was associated with hematotoxicity, but not the efficacy. We observed that renal dysfunction induced high blood concentration of pemetrexed.

      Conclusion
      The combination of carboplatin AUC5 and 500mg/m[2] of pemetrexed is promising for elderly chemo-naïve patients with advanced non-squamous NSCLC, but dose reduction of pemetrexed may be required for patients with renal dysfunction in further study.

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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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      P3.10-011 - Which do patients prefer as a first-line therapy, EGFR-TKI or chemotherapy, if they have NSCLC harboring EGFR mutation? A Vignettes study (LOGIK0903). (ID 1106)

      09:30 - 09:30  |  Author(s): J. Sasaki

      • Abstract

      Background
      Treatment decision-making is associated with potential decisional conflict of patients. Aim of this study was to determine the preferences of advanced NSCLC patients for EGFR-TKI or chemotherapy as first-line therapy if they were in the situation of having a lung cancer harboring EGFR mutation, and to investigate the variables considered important to that preference.

      Methods
      Three vignettes were designed to assess the patients’, the physicians’ or medical staff members’ preferences for treatment decision-making and the reasons classified into five category such as “evidence level”, “type of drug administration”, “therapeutic efficacy”, “adverse events”, and “influence to ordinary life” behind the decision. HADS, FACT-L and characteristics of participants including gender, age, and performance status (PS) are also investigated in this analysis.

      Results
      Total 377 individuals containing 100 patients, 100 physicians, and 177 medical staff members were analyzed in this study, and 322 participants (85.4%) preferred to EGFR-TKI than chemotherapy as a first-line therapy. Preference rate of EGFR-TKI in patients was statistically significantly lower than those in physicians and medical staffs, 73%, 88% and 91%, respectively. Among the reasons we investigated, “therapeutic efficacy” was the only marginal significant reason for preference in patients (odds ratio: 3.88, p=0.06). In addition to “therapeutic efficacy”, “type of drug administration” and “influence to ordinary life” was the significant reasons for their preference in physicians (odds ratio: 11.57, 22.57 and 20.5, respectively). In pre-planned analysis, we found the difference of value between the patients and the physicians in “influence to ordinary life”.

      Conclusion
      If the patients have an advanced lung cancer with EGFR mutation, they may prefer EGFR-TKI as a first-line therapy to chemotherapy as well as physicians and medical staff members. However the reasons of those preferences among them may be different. We should consider continuation of patients’ ordinary life when we discuss about treatment decision-making with patients.

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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): J. Sasaki

      • 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.