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Abstract
Purpose: Our goal was to evaluate the safety and toxicity of combining a PARP inhibitor, olaparib, with cetuximab and fractionated intensity-modulated radiotherapy for patients with locally advanced head and neck cancer and heavy smoking histories.Patients and Methods: Patients with ≥10 packs/year history of smoking were treated with olaparib at doses ranging from 25-200 mg orally twice daily beginning approximately 10 days prior to initiation of and with concurrent radiation (69.3 Gy in 33 fractions) using a time-to-event continual reassessment method model. Cetuximab was administered starting approximately 5 days prior to radiation per standard of care.Results: A total of 16 patients were entered onto the study, with 15 evaluable for acute toxicity. The most common treatment-related grade 3-4 side effects were radiation dermatitis and mucositis (38% and 69%, respectively). The MTD was determined to be 50 mg orally twice daily, but the recommended phase II dose was deemed to be 25 mg orally twice daily. At a median follow-up of 26 months, the actuarial median overall survival was 37 months, but was not reached for other endpoints. Two-year overall survival, progression-free survival, local control, and distant control rates were 72%, 63%, 72%, and 79%, respectively. Patients who continued to smoke during therapy experienced higher recurrence rates. MYC and KMT2A were identified as potential correlatives of response on gene amplification and mutational analysis.Conclusions: Olaparib at 25 mg orally twice daily with concurrent cetuximab and radiation was well tolerated with reduced dermatitis within the radiation field. Response rates were promising for this high-risk population.

Author information

Karam SD1, Reddy K2, Blatchford PJ3, Waxweiler T1, DeLouize AM1, Oweida A1, Somerset H4, Marshall C4, Young C4, Davies KD4, Kane M5, Tan AC5, Wang XJ4,6, Jimeno A4, Aisner DL4, Bowles DW4,6, Raben D7.
1
Department of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.
2
Department of Radiation Oncology, University of Toledo, Toledo, Ohio.
3
Department of Biostatistics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.
4
Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado.
5
Department of Medicine, Division of Medical Oncology, Anschutz Medical Campus, Aurora, Colorado.
6
Denver Veterans Affairs Medical Center, Eastern Colorado Health Care System, Denver, Colorado.
7
Department of Radiation Oncology, University of Colorado, Anschutz Medical Campus, Aurora, Colorado. david.raben@ucdenver.edu.