Citations 2
Progress and Opportunities to Advance Clinical Cancer Therapeutics Using Tumor Dynamic Models
Bruno, René , Bottino, Dean , Alwis, Dinesh P. de, Fojo, Antonio Tito, Swanson, Kristin R. , Zheng, Jenny, Zheng, Yanan , Swanson, Kristin R , Guedj, Jérémie , Liu, Chao , Jin, Jin Y.
Clinical Cancer Research | December 23, 2019 | Volume: 26 | Issue: 8 | Pages: 1787-1795
Abstract There is a need for new approaches and endpoints in oncology drug development, particularly with the advent of immunotherapies and the multiple drug combinations under investigation. Tumor dynamics modeling, a key component to oncology “model-informed drug development,” has shown a growing number of applications and a broader adoption by drug developers and regulatory agencies in the past years to support drug development and approval in a variety of ways. Tumor dynamics modeling is also being investigated in personalized cancer therapy approaches. These models and applications are reviewed and discussed, as well as the limitations and issues open for further investigations. A close collaboration between stakeholders like clinical investigators, statisticians, and pharmacometricians is warranted to advance clinical cancer therapeutics.
Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma
Frye, Robin, Turner, Maria L., Allen, Steven L. , Kirschbaum, Mark, Zain, Jasmine , Prince, H. Miles , Leonard, John P. , Geskin, Larisa J. , Reeder, Craig B. , Joske, David, Figg, William D. , Gardner, Erin R., Steinberg, Seth M. , Stetler‐Stevenson, Maryalice , Lade, Stephen , Fojo, Antonio Tito, Bates, Susan E. , Piekarz, Richard , Wright, John Joseph , Jaffe, Elaine S. , Prince, H Miles , Bates, Susan E
Journal of Clinical Oncology | October 14, 2009 | Volume: 27 | Issue: 32 | Pages: 5410-5417
Purpose Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. Conclusion The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL.