Shivaani Kummar

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We review the literature on primary hepatic lymphoma (PHL). PHL is a rare malignancy, and constitutes about 0.016% of all cases of non-Hodgkin's lymphoma. It has been reported to occur with increased frequency in patients with chronic hepatitis C infection. Most patients with PHL present with abdominal pain, constitutional symptoms and have hepatomegaly on(More)
PURPOSE We conducted the first phase 0 clinical trial in oncology of a therapeutic agent under the Exploratory Investigational New Drug Guidance of the US Food and Drug Administration. It was a first-in-human study of the poly (ADP-ribose) polymerase (PARP) inhibitor ABT-888 in patients with advanced malignancies. PATIENTS AND METHODS ABT-888 was(More)
PURPOSE Vorinostat is the first US Food and Drug Administration-approved histone deacetylase inhibitor and is indicated for the treatment of refractory cutaneous T-cell lymphoma. We conducted a phase I study to determine the maximum-tolerated dose and pharmacokinetics of vorinostat in patients with hepatic dysfunction. PATIENTS AND METHODS Patients had(More)
Wee1, a protein kinase, regulates the G 2 checkpoint in response to DNA damage. Preclinical studies have elucidated the role of wee1 in DNA damage repair and the stabilization of replication forks, supporting the validity of wee1 inhibition as a viable therapeutic target in cancer. MK-1775, a selective and potent small-molecule inhibitor of wee1, is under(More)
PURPOSE Phase I dose-escalation study to determine the toxicity and maximum tolerated dose (MTD) of 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, administered on a twice weekly schedule in patients with advanced cancer. EXPERIMENTAL DESIGN 17-DMAG was administered as a 1- to 2-h infusion twice(More)
PURPOSE Wee1 tyrosine kinase phosphorylates and inactivates cyclin-dependent kinase (Cdk) 1/2 in response to DNA damage. AZD1775 is a first-in-class inhibitor of Wee1 kinase with single-agent antitumor activity in preclinical models. We conducted a phase I study of single-agent AZD1775 in adult patients with refractory solid tumors to determine its(More)
PURPOSE Veliparib, a PARP inhibitor, demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase I trial. To define the relative contribution of PARP inhibition to the observed clinical activity, we conducted a randomized phase II trial to determine the response rate of veliparib in(More)
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Sorafenib is a multikinase inhibitor with activity against B-raf, C-raf, VEGFR2, PDGFRβ and FGFR1. Sorafenib is clinically approved for the treatment of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). The pharmacokinetics (PK) of sorafenib are highly variable between subjects. Sorafenib exposure(More)
PURPOSE To determine the safety and tolerability of olaparib with cisplatin and gemcitabine, establish the maximum tolerated dose (MTD), and evaluate the pharmacodynamic and pharmacokinetic profile of the combination. EXPERIMENTAL DESIGN We conducted a phase I study of olaparib with cisplatin and gemcitabine in patients with advanced solid tumors.(More)
There is an apparent need to improve the speed and efficiency of oncological drug development. Furthermore, strategies traditionally applied to the development of standard cytotoxic chemotherapy may not be appropriate for molecularly targeted agents. This is particularly the case for exploratory Phase 1 and 2 trials. Conventional approaches to determine(More)