PMID- 33231866 OWN - NLM STAT- MEDLINE DCOM- 20211014 LR - 20221207 IS - 1097-0142 (Electronic) IS - 0008-543X (Linking) VI - 127 IP - 6 DP - 2021 Mar 15 TI - A randomized, open-label, phase 2, multicenter trial of gemcitabine with pazopanib or gemcitabine with docetaxel in patients with advanced soft-tissue sarcoma. PG - 894-904 LID - 10.1002/cncr.33216 [doi] AB - BACKGROUND: Therapeutic options for patients with advanced soft-tissue sarcoma (STS) are limited. The goal of the current phase 2 study was to examine the clinical activity and safety of the combination of gemcitabine plus pazopanib, a multityrosine kinase inhibitor with activity in STS. METHODS: The current randomized, phase 2 trial enrolled patients with advanced nonadipocytic STS who had received prior anthracycline-based therapy. Patients were assigned 1:1 to receive gemcitabine at a dose of 1000 mg/m(2) on days 1 and 8 with pazopanib at a dose of 800 mg daily (G+P) or gemcitabine at a dose of 900 mg/m(2) on days 1 and 8 and docetaxel at a dose of 100 mg/m(2) on day 8 (G+T) every 3 weeks. Crossover was allowed at the time of disease progression. The study used a noncomparative statistical design based on the precision of 95% confidence intervals for reporting the primary endpoints of median progression-free survival (PFS) and rate of grade >/=3 adverse events (AEs) for these 2 regimens based on the intent-to-treat patient population (AEs were graded using version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events). RESULTS: A total of 90 patients were enrolled: 45 patients on each treatment arm. The median PFS was 4.1 months for each arm (P = .3, log-rank test). The best overall response of stable disease or better (complete response + partial response + stable disease) was the same for both treatment arms (64% for both the G+T and G+P arms). The rate of related grade >/=3 AEs was 82% for the G+T arm and 78% for the G+P arm. Related grade >/=3 AEs occurring in >/=10% of patients in the G+T and G+P arms were anemia (36% and 20%, respectively), fatigue (29% and 13%, respectively), thrombocytopenia (53% and 49%, respectively), neutropenia (20% and 49%, respectively), lymphopenia (13% and 11%, respectively), and hypertension (2% and 20%, respectively). CONCLUSIONS: The data from the current study have demonstrated the safety and efficacy of G+P as an alternative to G+T for patients with nonadipocytic STS. CI - (c) 2020 American Cancer Society. FAU - Somaiah, Neeta AU - Somaiah N AUID- ORCID: 0000-0002-0146-7732 AD - Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. FAU - Van Tine, Brian Andrew AU - Van Tine BA AUID- ORCID: 0000-0003-4572-6668 AD - Department of Medicine, Sarcoma Program Director, Washington University School of Medicine in St. Louis, St. Louis, Missouri. FAU - Wahlquist, Amy E AU - Wahlquist AE AD - Cancer Center, Medical University of South Carolina, Charleston, South Carolina. FAU - Milhem, Mohammed M AU - Milhem MM AD - Chief Section of Oncology, Department of Internal Medicine, University of Iowa, Iowa City, Iowa. FAU - Hill, Elizabeth G AU - Hill EG AD - Cancer Center, Medical University of South Carolina, Charleston, South Carolina. FAU - Garrett-Mayer, Elizabeth AU - Garrett-Mayer E AUID- ORCID: 0000-0003-4709-0333 AD - Center for Research and Analytics, American Society of Clinical Oncology, Alexandria, Virginia. FAU - Armeson, Kent E AU - Armeson KE AD - Cancer Center, Medical University of South Carolina, Charleston, South Carolina. FAU - Schuetze, Scott M AU - Schuetze SM AUID- ORCID: 0000-0002-7167-4163 AD - Division of Medical Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. FAU - Meyer, Christian F AU - Meyer CF AD - Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore, Maryland. FAU - Reuben, Daniel Y AU - Reuben DY AD - Cancer Center, Medical University of South Carolina, Charleston, South Carolina. FAU - Elias, Anthony D AU - Elias AD AD - Department of Internal Medicine, University of Colorado Comprehensive Cancer Center, Aurora, Colorado. FAU - Read, William L AU - Read WL AUID- ORCID: 0000-0001-6946-5250 AD - Division of Hematology/Oncology, Department of Medicine, , Emory Clinic, Atlanta, Georgia. FAU - Chawla, Sant P AU - Chawla SP AD - Sarcoma Oncology Research Center, Santa Monica, California. FAU - Kraft, Andrew S AU - Kraft AS AUID- ORCID: 0000-0003-3417-4845 AD - Department of Internal Medicine, University of Arizona Cancer Center, Tucson, Arizona. LA - eng GR - P30 CA08686217/CA/NCI NIH HHS/United States GR - P30 CA023074/CA/NCI NIH HHS/United States GR - P30 CA138313/CA/NCI NIH HHS/United States GR - P30 CA046592/CA/NCI NIH HHS/United States GR - Novartis/ GR - GlaxoSmithKline/ PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20201124 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Indazoles) RN - 0 (Pyrimidines) RN - 0 (Sulfonamides) RN - 0W860991D6 (Deoxycytidine) RN - 15H5577CQD (Docetaxel) RN - 7RN5DR86CK (pazopanib) RN - 0 (Gemcitabine) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Cross-Over Studies MH - Deoxycytidine/administration & dosage/adverse effects/*analogs & derivatives MH - Docetaxel/*administration & dosage/adverse effects MH - Female MH - Humans MH - Indazoles/*administration & dosage/adverse effects MH - Male MH - Middle Aged MH - Pyrimidines/*administration & dosage/adverse effects MH - Soft Tissue Neoplasms/*drug therapy/mortality MH - Sulfonamides/*administration & dosage/adverse effects MH - Young Adult MH - Gemcitabine OTO - NOTNLM OT - adverse events OT - best overall response OT - gemcitabine and pazopanib OT - soft-tissue sarcoma EDAT- 2020/11/25 06:00 MHDA- 2021/10/15 06:00 CRDT- 2020/11/24 12:13 PHST- 2020/06/24 00:00 [received] PHST- 2020/08/10 00:00 [revised] PHST- 2020/08/20 00:00 [accepted] PHST- 2020/11/25 06:00 [pubmed] PHST- 2021/10/15 06:00 [medline] PHST- 2020/11/24 12:13 [entrez] AID - 10.1002/cncr.33216 [doi] PST - ppublish SO - Cancer. 2021 Mar 15;127(6):894-904. doi: 10.1002/cncr.33216. Epub 2020 Nov 24.