A Phase I Dose-Escalation Study of Veliparib Combined with Carboplatin and Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer and Other Solid Tumors
| Autor: | Florence Atrafi, Young Kwang Chae, Martijn P. Lolkema, Philip Komarnitsky, Lauren Averett Byers, Lei He, Tian Tian, Santiago Viteri, Beibei Hu, Silpa Nuthalapati, Randeep Sangha, Antonio Calles, Nashat Y. Gabrail, Elena Garralda, Harry J.M. Groen, Elizabeth Hoening, D. Ross Camidge |
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| Přispěvatelé: | Medical Oncology, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Oncology Cancer Research medicine.medical_treatment ABT-888 SINGLE-AGENT Carboplatin chemistry.chemical_compound 0302 clinical medicine Neoplasms Antineoplastic Combined Chemotherapy Protocols Etoposide PLUS CARBOPLATIN Middle Aged CHEMOTHERAPY Treatment Outcome Tolerability 030220 oncology & carcinogenesis DNA-REPAIR Female TRIAL medicine.drug Adult medicine.medical_specialty Maximum Tolerated Dose Veliparib Neutropenia GERMLINE BRCA1 OVARIAN-CANCER 03 medical and health sciences Pharmacokinetics SDG 3 - Good Health and Well-being Internal medicine medicine Humans Adverse effect PARP INHIBITOR VELIPARIB COMBINATION Aged Neoplasm Staging Chemotherapy business.industry medicine.disease Small Cell Lung Carcinoma 030104 developmental biology chemistry Benzimidazoles business |
| Zdroj: | Clinical Cancer Research, 25(2), 496-505. American Association for Cancer Research Inc. Clinical Cancer Research, 25(2), 496-505. AMER ASSOC CANCER RESEARCH |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: This study examined safety, pharmacokinetics, and efficacy of veliparib, a PARP inhibitor, combined with carboplatin and etoposide in patients with extensive-stage (ED) small cell lung cancer (SCLC) and other solid tumors. Patients and Methods: The 3 + 3 design was used for dose escalation of oral veliparib in combination with carboplatin (AUC 5 on day 1) and etoposide (100 mg/m2 on days 1–3) in 21-day cycles. Veliparib dose was explored from 80 to 240 mg b.i.d. on 7-day, 14-day, or continuous schedules. Patients without disease progression continued on maintenance monotherapy (veliparib 400 mg b.i.d.) until disease progression or unacceptable toxicity. Results: Thirty-nine patients were enrolled to determine the recommended phase II dose of 240 mg veliparib for 14 days combined with carboplatin and etoposide based on long-term tolerability. Dose-limiting toxicity occurred in 1 patient (grade 2 toxic motor polyneuropathy) at veliparib 240 mg b.i.d. for 7 days. Most common adverse events related to veliparib were nausea (39%), fatigue (39%), and hematologic toxicities. Continuous dosing of veliparib 240 mg b.i.d. with carboplatin and etoposide resulted in excessive chemotherapy dose delays due to hematologic toxicity (grade 3/4 neutropenia/thrombocytopenia). Etoposide pharmacokinetics was not affected by veliparib. Confirmed responses occurred in 17 of 39 (44%) and 16 of 25 (64%) of all enrolled and ED SCLC patients, respectively. At the RP2D, confirmed responses occurred in 6 of 13 (46%) and 5 of 6 (83%) of all enrolled and ED SCLC patients, respectively. Conclusions: Veliparib (240 mg b.i.d. 14 days) plus carboplatin/etoposide can be safely combined. Phase II of this study is ongoing in first-line patients with ED SCLC. |
| Databáze: | OpenAIRE |
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