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I. Kawase



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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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      P1.10-015 - Phase II study of pemetrexed plus intermittent erlotinib combination therapy for pretreated advanced non-squamous non-small cell lung cancer with documentation of epidermal growth factor receptor mutation status (ID 959)

      09:30 - 09:30  |  Author(s): I. Kawase

      • Abstract

      Background
      Erlotinib and pemetrexed are recommended for the second-line treatment of non-small cell lung cancer (NSCLC). With the recommended doses determined by our previous phase I study [BMC Cancer 2012;12(1):296], we conducted a phase II study to evaluate the efficacy and safety of combination of the two agents in patients with pretreated non-squamous NSCLC.Erlotinib and pemetrexed are recommended for the second-line treatment of non-small cell lung cancer (NSCLC). With the recommended doses determined by our previous phase I study [BMC Cancer 2012;12(1):296], we conducted a phase II study to evaluate the efficacy and safety of combination of the two agents in patients with pretreated non-squamous NSCLC.

      Methods
      Patients with stage III/IV or post-surgically recurrent non-squamous NSCLC whose disease had progressed after first-line chemotherapy were enrolled. Patients received 500 mg/m[2] of intravenous pemetrexed every 21 days and 150 mg of oral erlotinib on days 2–16 until disease progression or unacceptable toxicity. The primary objective was the response rate (RR). The secondary objectives were the disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety.

      Results
      A total of 27 patients, 16 males and 11 females, with the median age of 70 (range, 48–80) were enrolled. They included 21 stage IV diseases and 22 adenocarcinomas. The Epidermal growth factor receptor (EGFR) gene mutations were examined in all patients and only one patient was positive. The median number of treatment courses was 3 (range, 1 to over 19). The RR and DCR were 11.1% and 63.0%. The median PFS and OS were 2.8 months (95% confidence interval (CI); 1.9 to 7.5) and 15.8 months (95% CI; 9.3 to not available), respectively. As for safety, dermal, hepatic, gastrointestinal and hematological disorders were the frequently observed adverse events. Grade 3/4 toxicities observed in more than 15% patients were neutropenia (n = 10), anemia (n = 6), febrile neutropenia (n = 6), ande anorexia (n = 5). One patient experienced grade 3 drug-induced interstitial lung disease.

      Conclusion
      We could not demonstrate the add-on effect of intermittent erlotinib on pemetrexed in the second-line treatment of non-squamous NSCLC without EGFR mutations.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.10-007 - Phase II trial of Pemetrexed and Carboplatin followed by Pemetrexed continuation-maintenance therapy in previously untreated advanced non-small cell lung cancer (ID 679)

      09:30 - 09:30  |  Author(s): I. Kawase

      • Abstract

      Background
      Survival benefits of pemetrexed for advanced non-squamous non-small cell lung cancer (NSCLC) have been demonstrated in both switch- and continuation-maintenance settings after platinum-based induction. A phase III trial (PARAMOUNT) comparing pemetrexed maintenance with best supportive care after 4 cycles of induction pemetrexed plus cisplatin in non-squamous NSCLC patients demonstrated benefits both in progression-free-survival (PFS) and overall survival (OS) by pemetrexed continuation-maintenance. However, it remained undetermined whether pemetrexed could improve survival when it was continued to administer after carboplatin plus pemetrexed induction. We conducted a phase II study to evaluate the efficacy and safety of this regimen.

      Methods
      Thirty-four chemonaïve patients with stage IIIB/IV or postoperative recurrent non-squamous NSCLC received carboplatin (area under the concentration-time curve 6 mg/mL/min, day 1) plus pemetrexed (500 mg/m[2], day 1) every 3 weeks. Non-progressive patients after 4 cycles of induction received pemetrexed maintenance (500 mg/m[2], day 1) every 3 weeks until disease progression or unacceptable toxicity. The primary objective was to investigate 1-year survival rate. Secondary objectives were to investigate the safety, the objective response rate (ORR) during induction chemotherapy and PFS, defined as the time from enrollment to disease progression or death.

      Results
      From December 2009 to March 2011, a total of 34 patients were enrolled. The median follow-up time was 20.9 months (range, 2 to 32.3). At the time of the data collection, 19 patients were dead, 13 still alive, 2 lost follow-up. Twenty-five patients (73.5%) completed induction and 22 patients (64.7%) received maintenance therapy. The 1-year survival rate was 70.3% (95% CI, 53.0 to 83.2). The 2-year survival rate was 45.5% (95% CI, 28.7 to 63.5). The median PFS and OS were 5.2 months (95% CI, 4.1 to 8.2) and 23.0 months (95% CI, 15.5 to not available) from enrollment in all 34 patients, in addition 9.0 months (95% CI, 5.2 to 12.1) and 24.3 months (95% CI, 17.8 to not available) from the start of maintenance therapy in 22 patients who proceeded to maintenance therapy. The objective response rate and the disease control rate were 32.4% and 88.2%. The incidental rates of grade 3 or more severe adverse events were low except for one case of grade 5 pneumonitis. A multivariate analysis of 21 patients who received maintenance therapy with any tumor regression showed that the longer time to the best response achievement, positive epidermal growth factor receptor mutation status and better Karnofsky performance status contributed to achieve longer PFS.

      Conclusion
      Pemetrexed continuation-maintenance following pemetrexed plus carboplatin induction is a promising treatment for chemonaïve patients with advanced non-squamous NSCLC because of its good efficacy and less cumulative toxicities. This regimen could be substitutable for pemetrexed continuation-maintenance following cisplatin-based induction.

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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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      P3.10-015 - Final analysis of dose escalation study of carboplatin plus pemetrexed followed by maintenance pemetrexed for elderly patients (≥75 years old) with advanced non-squamous non-small cell lung cancer (ID 1349)

      09:30 - 09:30  |  Author(s): I. Kawase

      • Abstract

      Background
      This study was designed to determine the recommended dose of carboplatin plus pemetrexed in elderly (≥75 years old), chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer (NSCLC).Patients and methods: Patients received escalated doses of carboplatin and pemetrexed every 3 weeks for 4 cycles. Patients with an objective response and stable disease continued pemetrexed therapy until disease progression or unacceptable toxicity was observed.

      Methods
      Patients received escalated doses of carboplatin area under the concentration–time curve (AUC) of 4 (cohort 0) or 5 (cohort 1) or 6 (cohort 2) and pemetrexed 500mg/m2 every 3 weeks for 4 cycles. Patients with an objective response and stable disease continued pemetrexed therapy until disease progression or unacceptable toxicity was observed.

      Results
      In cohort 0, a dose-limiting toxicity (DLT) was not observed in three patients, and no DLTs were seen in the first three patients of cohort 1. In cohort 2, DLTs were observed in three of the seven patients: two of grade 4 thrombocytopenia and one of grade 3 febrile neutropenia. And in additional cohort 1, no DLTs were seen in the next four patients. Therefore, the combination of carboplatin at an area under the concentration–time curve (AUC) of 5, plus 500 mg/m[2 ]pemetrexed, was determined to be the recommended dose for elderly patients (≥75 years old) with advanced non-squamous NSCLC. Of a total of 17 patients, 10 received a median of 5 cycles of pemetrexed maintenance therapy without unexpected or cumulative toxicities. No complete responses and 8 partial responses were observed, and the study had an overall response rate of 47.1%. The median progression-free survival time was 5.5 monthes (95% confidence interval [CI], 2.4–8.9 monthes) and the median overall survival time was 12.6 monthes (95% CI, 7.4–17.9 monthes) in he final analysis of this study.

      Conclusion
      Figure 1 This combination was a tolerable and effective regimen, and recommended dose was carboplatin (AUC of 5) / pemetrexed (500 mg/m2) every 3 weeks, in chemotherapy-naïve, elderly (≥75 years old) patients with advanced non-squamous NSCLC.

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      P3.10-019 - Oral S-1 and carboplatin followed by maintenance S-1 for chemo-naive patients with advanced squamous cell lung cancer (OSAKA-LCSG 1102) (ID 1384)

      09:30 - 09:30  |  Author(s): I. Kawase

      • Abstract

      Background
      The subset analysis of LETS study suggested that S-1 plus carboplatin was more beneficial than paclitaxel plus carboplatin in overall survival (OS) in squamous cell lung cancer. We previously showed the validity of tailored dose S-1 adjusted by BSA and Ccr. No maintenance study focusing on squamous cell lung cancer has been reported yet. Here, we conducted a phase II study to evaluate the efficacy and safety of tailored dose S-1 plus carboplatin followed by S-1 maintenance in chemonaïve patients with advanced and recurrent squamous cell lung cancer.

      Methods
      Patients receive carboplatin (AUC = 5, day1) plus S-1 (tailored dose b.i.d., days 1-14) every 21 days. Non-progressive patients after 4 cycles of induction continued to receive S-1 until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) with a threshold value of 15%. The secondary endpoints were progression-free survival (PFS) and OS from enrollment, PFS in maintenance phase, and safety.

      Results
      Between April 2011 and October 2012, 35 patients were enrolled. Thirty-three patients excluding 2 patients with protocol violations were analyzed. The median age was 72 years (range, 44-82), The ORR was 30.3% (95% CI: 15.6-48.7%) that met the primary endpoint. Disease control rate was 75.8%, and 10 patients (30.3%) received maintenance therapy. The median PFS was 3.7 months. The median OS and maintenance PFS are under follow-up. 10 patients received maintenance S-1 (median: 3 cycles, range: 1-9 cycles); median PFS from the beginning of induction treatment was 5.6 months. Grade 3/4 toxicities with the frequency more than 5% included 4 neutropenia (12.1%), 7 thrombocytopenia (21.2%), 2 anemia (6.1%), 4 appetite loss (12.1%), 2 nausea (6.1%) and 2 fatigue (6.1%). All of them were controllable and febrile neutropenia was not experienced.

      Conclusion
      This is the first trial of S-1 plus carboplatin followed by maintenance S-1 for chemo-naïve advanced and recurrent squamous cell lung cancer. This treatment strategy was effective and feasible.