Author of

• 12592

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

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 2
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12604

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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. Hida
    • 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. Hida
    • 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.