Michael J Jelinek1, Nathan R Foster2, Alex J Zoroufy2, Gary K Schwartz3, Pamela N Munster4, Tanguy Y Seiwert5, Jonas A de Souza6, Everett E Vokes5. 1. Department of Medicine, Section of Hematology/Oncology, University of Chicago Medicine and Biological Sciences, Chicago, IL, USA; Department of Medicine, Division of Hematology, Oncology, and Cell Therapy, Rush University Medical Center, Chicago, IL, USA(1). Electronic address: Michael_Jelinek@rush.edu. 2. Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA. 3. Department of Medicine, Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA. 4. Department of Medicine, Section of Hematology/Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, UCSF Medical Center-Mount Zion, San Francisco, CA, USA. 5. Department of Medicine, Section of Hematology/Oncology, The University of Chicago Comprehensive Cancer Center, Chicago, IL, USA. 6. Department of Medicine, Section of Hematology/Oncology, University of Chicago Medicine and Biological Sciences, Chicago, IL, USA.
Abstract
OBJECTIVES: We report the results of this phase I study to evaluate the maximum tolerated dose (MTD) and safety of veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin and paclitaxel induction chemotherapy (IC) for locoregionally advanced head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: In a 3 + 3 cohort design, patients with stage IVA-B human papillomavirus-negative HNSCC received 2 cycles of carboplatin (AUC 6, day 1), paclitaxel (100 mg/m2, days 1, 8, 15) and veliparib (days 1-7) every 21 days followed by standard curative-intent chemoradiotherapy. Primary endpoint: MTD and recommended phase II dose (RP2D) as determined by the first IC cycle. RESULTS: Twenty patients enrolled. Two withdrew before treatment; 18 patients were analyzed. Median age was 63 years. Primary disease sites included hypopharynx (n = 5), larynx (n = 5), oral cavity (n = 4), oropharynx (n = 3), and nasal cavity (n = 1). Through all of IC, the most common grade 3 + adverse events (AEs) were neutropenia (33%), thrombocytopenia (33%), anemia (11%), and white blood cell decrease (11%). One patient experienced a hematologic DLT at 350 mg BID. The RP2D for veliparib combined with carboplatin/paclitaxel is 350 mg BID. With 40.9 month median follow-up across dose levels for all patients, the 24-month overall and progression free survival was 77.8% (95% CI 60.8-99.6%) and 66.7% (95% CI 48.1-92.4%), respectively. Medians have not been reached. CONCLUSION: Addition of veliparib to carboplatin and paclitaxel IC was well tolerated in patients with advanced HNSCC. Hematologic toxicities were the most common AEs.
OBJECTIVES: We report the results of this phase I study to evaluate the maximum tolerated dose (MTD) and safety of veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin and paclitaxel induction chemotherapy (IC) for locoregionally advanced head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: In a 3 + 3 cohort design, patients with stage IVA-B human papillomavirus-negative HNSCC received 2 cycles of carboplatin (AUC 6, day 1), paclitaxel (100 mg/m2, days 1, 8, 15) and veliparib (days 1-7) every 21 days followed by standard curative-intent chemoradiotherapy. Primary endpoint: MTD and recommended phase II dose (RP2D) as determined by the first IC cycle. RESULTS: Twenty patients enrolled. Two withdrew before treatment; 18 patients were analyzed. Median age was 63 years. Primary disease sites included hypopharynx (n = 5), larynx (n = 5), oral cavity (n = 4), oropharynx (n = 3), and nasal cavity (n = 1). Through all of IC, the most common grade 3 + adverse events (AEs) were neutropenia (33%), thrombocytopenia (33%), anemia (11%), and white blood cell decrease (11%). One patient experienced a hematologic DLT at 350 mg BID. The RP2D for veliparib combined with carboplatin/paclitaxel is 350 mg BID. With 40.9 month median follow-up across dose levels for all patients, the 24-month overall and progression free survival was 77.8% (95% CI 60.8-99.6%) and 66.7% (95% CI 48.1-92.4%), respectively. Medians have not been reached. CONCLUSION: Addition of veliparib to carboplatin and paclitaxel IC was well tolerated in patients with advanced HNSCC. Hematologic toxicities were the most common AEs.
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