Virtual Library

Start Your Search

N. Blais



Author of

  • +

    MINI 15 - Chemotherapy Developments for Lung Cancer (ID 128)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Advanced Diseases - NSCLC
    • Presentations: 1
    • +

      MINI15.03 - Phase I & II Studies of the Decitabine-Genistein Drug Combination in Advanced Solid Tumours (ID 1091)

      16:45 - 18:15  |  Author(s): N. Blais

      • Abstract
      • Presentation
      • Slides

      Background:
      The combination of epigenetic drug decitabine with genistein, a natural isoflavone, produces synergistic responses in preclinical studies with particular activity shown in lung cancer cell lines. Our phase I dose-escalation study of decitabine with a fixed dose of genistein to treat advanced solid tumor was followed by a phase II study in advanced lung cancer patients.

      Methods:
      In phase I, decitabine was administered over 10-hours at increasing doses (60, 120, 240 mg/m[2]) with continuous administration of genistein 300 mg/day orally. The MTD was 120 mg/m[2] with neutropenia as DLT. Decitabine at 120 mg/m[2 ]and genistein produced plasma levels of 0.62±0.06 µM and 8.5±5.6 µM, respectively.

      Results:
      The drug combination was well tolerated and produced stable disease for more than 6 months (7-14 months) in 5/10 patients. One gastric cancer patient had a 50% reduction in tumor burden after 6 months of therapy. Stable disease was also achieved in patients with desmoplastic small round cell tumor, oncocytic carcinoma, follicular thyroid carcinoma and bladder cancer. The phase II study was focused on nine patients with non-small cell lung cancer refractory to 3-4 lines of therapy. Eight progressed within the first radiologic evaluation at week 6. One NSCLC patient remains on therapy with SD after 3 months of treatment. A total of 60 adverse events were reported during the study with all patients experiencing at least one AE. Grade 3 & 4 treatment related toxicities were observed in 6/9 patients (66%) : neutropenia (4) anemia (2) febrile neutropenia (1) and hypertension (1).

      Conclusion:
      This combination of genistein with decitabine was well tolerated in advanced patients with solid tumors. The activity of the combination seen in some patients with tumors of more indolent biology was modest in the phase II cohort of heavily pretreated NSCLC patients. The efficacy profile observed in this trial suggests that tumors with slower tumor kinetics might benefit more from this type of epigenetic therapy.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.