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M. Tsuboi



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    P2.12 - Poster Session 2 - NSCLC Early Stage (ID 205)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.12-022 - A feasibility study of postoperative adjuvant chemotherapy with fluoropyrimidine S-1 in patients with stage II-IIIA non-small cell lung cance (ID 3352)

      09:30 - 09:30  |  Author(s): M. Tsuboi

      • Abstract

      Background
      S-1 is an orally active combination of tegafur, gimeracil and oteracil in a molar ratio of 1:0.4:1. We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathologically stage II-IIIA non-small cell lung cancer (NSCLC).

      Methods
      Patient eligibility required compliance with the following criteria: histologically proved NSCLC; pathologic stage II-IIIA (according to the Union for International Cancer Control 6th edition) after complete resection; no previous treatment except for surgery; age >=20 and <80 years; performance status (PS) 0 or 1; no organ dysfunction; no concurrent malignancy; and written informed consent. Chemotherapy comprised 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg per day according to body surface area and renal function. The primary end point was the completion rate of scheduled adjuvant chemotherapy. Secondary end points were safety, overall survival and relapse-free survival. From November 2007 through December 2010, 24 patients were enrolled in this trial.

      Results
      Patient characteristics were as follows: median age of 68 (range: 49-79); male/female: 16/8; surgical procedure lobectomy/pneumonectomy: 21/3; pathologic stage IIA/IIB/IIIA: 8/6/10; and histologic type adenocarcinoma/squamous cell carcinoma/other: 19/4/1. Three patients were censored due to the disease recurrence, and the completion rate of 9 courses was calculated to be 42.9% (9/21). Completion rate of more than 70% of scheduled 9 courses was 61.9% (13/21). Most common adverse events were grade 1 or 2 anorexia (54.2%) or fatigue (20.8%), which were reasons of discontinuation of S-1 administration. Although grade 3 elevated total bilirubin (4.2%) and pneumonitis (4.2%) were observed, no grade 4 or 5 adverse events occurred. Overall and relapse-free survival rates at 3 years were 69.5% and 51.1%, respectively. Patients who completed more than 70% of scheduled 9 courses showed better relapse-free survival than 70% uncompleted patients (p=0.01).

      Conclusion
      Postoperative administration of S-1 seems feasible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathologically stage II-IIIA NSCLC.

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    P3.05 - Poster Session 3 - Preclinical Models of Therapeutics/Imaging (ID 159)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.05-015 - Positron-emission tomography-computed tomography with the glucose analogue [18F] fluorodeoxyglucose in orthotopic implantation SCID mouse model of lung cancer (ID 2619)

      09:30 - 09:30  |  Author(s): M. Tsuboi

      • Abstract

      Background
      In vivo evaluation is essential for development of lung cancer treatment. However, the subcutaneous xenograft models are not closely reproducing microenvironment of lung cancer. Although orthotopic implantation SCID mouse model of lung cancer presents lymphatic metastasis to mediastinum or pleuritis carcinomatosa with progression of disease, it has been difficult to evaluate the efficacy of treatment without sacrifice of model mouse. Positron-emission tomography-computed tomography (PET-CT) with the glucose analogue [18F] fluorodeoxyglucose (FDG) has been recently applied for evaluating tumor response to anticancer therapy. We have evaluated the utility of FDG PET-CT in orthotopic implantation SCID mice model of lung cancer.

      Methods
      Animals: 6 weeks male SCID mice (n=12). Cell line: Ma44-3 cloned from Ma44 (human squamous cell lung cancer cell line). Under sufficient anesthesia, mice were placed in the left lateral decubitus position. A 1-cm transverse incision was made in the right lateral skin just below the inferior border of the scapula. After intercostal muscles were exposed, 2 x 10[6] tumor cells/ml with 400 μg/ml Matrigel® was injected into the right lung in a volume of 10 μl (2.0x10[4 ]cells) of medium. Four or 5 days after implantation (6 mice on day 4 and other 6 mice on day 5), the SCID mice were examined with FDG PET-CT and mice whose lung tumors were identified were randomized to treatment group and control group. Treatment group mice received intraperitoneal injection of cisplatin (7mg/kg) on day 6 after implantation. All mice were examined with FDG PET-CT on day 8 and 13 after implantation. Tumor volume and maximal standardized uptake value (SUV max) of the lung tumor were calculated for all mice. All SCID mice were sacrificed on day 13 after implantation for histopathologic analysis.

      Results
      Six mice whose lung tumors were identified at the first FDG PET-CT were randomized to treatment group (n=3) and control group (n=3). The average growth rates (day 13 versus day 5 or 6) of tumor volume and SUV max of the treatment group were 144% and 108%, respectively, whereas the average growth rates of tumor volume and SUV max of the control group were 1470% and 271%, respectively.

      Conclusion
      Tumor growth and inhibition were evaluated by FDG PET-CT in orthotopic implantation SCID mice model of lung cancer. This in vivo evaluation system is useful for development of lung cancer treatment.