title: Phase Ib/II trial of gemcitabine, cisplatin, and lenalidomide as first-line therapy in patients with metastatic urothelial carcinoma.
abstract: BACKGROUND
  Outcomes with current chemotherapy in metastatic urothelial carcinoma (MUC) remain poor. Lenalidomide, an antiangiogenic and immunomodulatory agent, enhances the effects of chemotherapy in preclinical studies. In this phase Ib/II study, we sought to determine a tolerable dose of lenalidomide in combination with gemcitabine and cisplatin (GCL) in patients with MUC and to explore the safety and activity of this regimen.
  
  
  METHODS
  Patients with chemotherapy-naïve MUC received gemcitabine 1,000 mg/m(2) on days 1 and 8 and cisplatin 70 mg/m(2) on day 1 every 21 days. In phase Ib, there were four planned escalating dose levels of lenalidomide (10, 15, 20, and 25 mg) daily on days 1-14.
  
  
  RESULTS
  Seven patients received GCL in phase Ib. The dose of lenalidomide was not escalated beyond 10 mg because of cytopenias requiring repeated dose delays and reductions. Two additional patients were enrolled in phase II, but the study was ultimately terminated due to poor tolerability and slow accrual. The most frequent grade ≥ 3 adverse events were cytopenias and diarrhea. Three of the nine patients experienced an objective response (one complete response, two partial responses).
  
  
  CONCLUSIONS
  Chronic administration of the GCL regimen was poorly tolerated because of additive and cumulative myelosuppression.
authors: Department of Medicine, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA;
authors: Neeraj
authors: N
authors: Agarwal
authors: Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA;
authors: Andrea B
authors: AB
authors: Apolo
authors: Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Che-Kai
authors: CK
authors: Tsao
authors: Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Karen M
authors: KM
authors: Lee
authors: Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: James H
authors: JH
authors: Godbold
authors: Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Rothschild
authors: R
authors: Soto
authors: Department of Medicine, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA;
authors: Austin
authors: A
authors: Poole
authors: Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Kiev
authors: K
authors: Gimpel-Tetra
authors: Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: Nancy
authors: N
authors: Lowe
authors: Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors: William K
authors: WK
authors: Oh
authors: Department of Medicine, Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA matthew.galsky@mssm.edu.
authors: Matthew D
authors: MD
authors: Galsky
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D006801:Humans; D000077269:Lenalidomide; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019459:Urothelium / Q000187:drug effects / Q000473:pathology*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D013792:Thalidomide; D000077269:Lenalidomide; D002945:Cisplatin; D000093542:Gemcitabine