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B. Holm



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    P3.08 - Poster Session 3 - Radiotherapy (ID 199)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P3.08-023 - Acute Esophagitis and concomittant Chemoradiotherapy with Navelbine. Results from NARLAL, a Phase II randomized Trial. (ID 2686)

      09:30 - 09:30  |  Author(s): B. Holm

      • Abstract

      Background
      Radiotherapy (RT) for non-small cell lung cancer (NSCLC) is associated with important side effects with acute esophagitis (AE) as one of the main acute toxicities. RT dose and concomitant chemo-radiotherapy as well as volume of oesophagus treated are known risk factors for development of AE.

      Methods
      This is a multicentre national protocol on RT for locally advanced NSCLC. From 2009-2013 117 patients were randomized between 60 Gy/ 30 F (arm A) and 66 Gy/ 33 F (Arm B), 5 FW. Navelbine[®] 50 mg 3 days a week was given concomitant with RT. Before randomization patients were treated with 2 cycles of carboplatin and Navelbine[®] as induction chemotherapy. During RT, patients were registered for side effects once a week. After RT follow up schedule was every 3[th] month from RT start. Side effects were registered according to NCI CTCAE version 3.

      Results
      A total of 117 patients were randomized in this protocol. Baseline characteristics are summarized in table 1. Since last patient was randomized August 2013, all CRF are not available for the moment. There are complete esophagitis data on 103 patients. Grade 0-1 AE were seen in 66 patients (37 in arm A vs. 29 in Arm B), grade 2 in 27 patients (11 vs. 16), 10 patients experienced grade 3 (3 vs. 7), and none grade 4 AE. In a logistic regression analysis with N2/3, age ≥64 years, histology, gender and dose as covariates; treatment arm B was the only significant covariate (p=0.02) for developing grade 2 esophagitis. Dose volumetric data will be ready for WCLC.Figure 1

      Table 1 Number %
      Performance status 0 59 50
      1 57 49
      missing 1 1
      Gender Male 68 58
      Female 49 42
      Histology Squamos cell carcinoma 41 35
      Adenocarcinoma 54 46

      Conclusion
      From this study we conclude, that the risk of developing grade 2 esophagitis is related to dose 66 Gy but the severity is manageable. Acknowledgements Supported by CIRRO- The Lundbeck Foundation Center for Interventional Research in Radiation Oncology.

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    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.11-030 - A phase I / II trial of the HDAC inhibitor belinostat in combination with erlotinib in patients with non-small cell lung cancer. (ID 2369)

      09:30 - 09:30  |  Author(s): B. Holm

      • Abstract

      Background
      Belinostat (PXD101), is a histone deacetylase (HDAC) inhibitor. HDAC inhibitors, including belinostat, have shown marked in vitro and in vivo activity against a number of solid tumors and hematological cancers. Belinostat is efficient as a single agent as well as in combination with other anticancer agents such as doxorubicin, paclitaxel, carboplatin, fluorouracil, bortezumib. Synergistic effect between HDAC inhibitors, incl. belinostat and EGFR inhibitors has been observed. Belinostat has been well tolerated at doses up to 2000 mg daily in patients. The main side effects are fatigue, nausea and vomiting. The trial was designed as an open, non-randomized phase I / II trial to assess the efficacy and safety of belinostat in combination with erlotinib in patients with advanced non-small cell lung cancer, who were eligible for treatment with erlotinib.

      Methods
      The primary endpoint of the phase I part was to establish the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of erlotinib (150mg/d) in combination with increasing doses of belinostat. The study was designed as a 3+3 phase I trial. All patients began with 4 weeks of erlotinib 150 mg/d. If this was tolerated, patients started the combination erlotinib and belinostat. The belinostat dose steps were 500 mg, 1000 and 1500 mg, administered daily in 2 weeks on treatment, 1 week off treatment. When one patient was enrolled at one dose level, there would be no further dose escalation for that individual patient. Three patients were planned at each dose level. When the MTD was identified the trial was planned to expand to a phase II trial, and include 20 patients with non-small cell lung cancer.

      Results
      From October 2010 until June 2011 five patients were enrolled in the phase I part of the trial. Patient one and two started belinostat 500 mg after four weeks of erlotinib 150 mg/d.Both patients experienced grade 3 diarrhea in spite of supportive care with loperamid and antiemitics. The treatment was discontinued in both patients and the toxicity quickly resolved. In accordance with the trial protocol, patient three was started on belinostat 250 mg. Patient three experienced only grade 1 diarrhea and grade 1 nausea. The patient received 2 series of belinostat. Patient four experienced grade 2 diarrhea and grade 2 rash in the first series belinostat 250 mg. Patient five experienced, in the first series of belinostat, grade 3 diarrhea and was hospitalized despite intensive supportive care. All patients discontinued treatment and toxicity resolved.

      Conclusion
      The combination of the HDAC-inhibitor belinostat and the EGFR inhibitor erlotinib resulted in severe toxicity. The trial has been closed. NCT01188707