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T. Kozuki



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    P1.15 - Poster Session 1 - Thymoma (ID 189)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Thymoma & Other Thoracic Malignancies
    • Presentations: 1
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      P1.15-003 - Phase II study of amrubicin (AMR) and carboplatin (CBDCA) for invasive thymoma (IT) and thymic carcinoma (TC) : North Japan Lung Cancer Group 0803 (ID 951)

      09:30 - 16:30  |  Author(s): T. Kozuki

      • Abstract

      Background
      There has been no standard chemotherapy for advanced thymic malignancies including invasive thymoma(IT) and thymic carcinoma(TC) although anthracycline or platinum agents have been commonly used for them. AMR, a new anthracycline agent, was approved for lung cancer in Japan and we had previously conducted some prospective studies of AMR combined with CBDCA for patients with small-cell lung cancer, which revealed this regimen was active with acceptable toxicity. The objective of this study is to evaluate the efficacy and safety of this combination for patients with advanced thymic malignancies.

      Methods
      Patients with histologically confirmed thymic malignancies received AMR (35 mg/m2, day1-3) and CBDCA (AUC 4.0, day1) every 3 weeks. Patients who underwent previous chemotherapy received reduced dose of AMR (30 mg/m2). The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival and toxicity profile. Assuming that ORR of 75% and 45% would indicate the potential usefulness while ORR of 50% and 20% would be the lower limit of interest, with alpha = 0.10 and beta = 0.20, for IT patients and TC patients, respectively, 18 IT patients and 16 TC patients were at least required.

      Results
      From December 2008 to October 2012, 51 patients (18 IT and 33 TC) were enrolled from 20 institutions in Japan. The ORR and disease control rate were 17% and 89% in IT, and 30% and 85% in TC. Median PFS was 7.6 months in both groups. Toxicity was generally moderate and no treatment related death was observed.

      Conclusion
      This is the largest prospective study of chemotherapy for advanced thymic malignancies. AMR combined with CBDCA was effective for TC patients with acceptable toxicities.

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

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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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 - 16:30  |  Author(s): T. Kozuki

      • 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.