Pharmacy & Therapeutics - December 2008 - (Page 712)

MEETING HIGHLIGHTS Chemotherapy Foundation Symposium XXVI Innovative Cancer Therapy for Tomorrow Mar vin M. Goldenberg, PhD, RPh, MS The mission of the 26th annual Chemotherapy Foundation Symposium, which took place in New York City from November 4 to 7, 2008, was to communicate the extensive scope and intensive coverage of emerging advances in the treatment of many neoplastic diseases. Almost 2,200 oncologists, hematologists, radiotherapists, immunologists, pharmacists, nurses, nurse-practitioners, physician assistants and other allied health care professionals, and representatives of the pharmaceutical industry attended. This article summarizes some of the important research and development in the various areas of oncology. Complete remission and a reduction in bone marrow blasts to less than 5% correlated with the time above a threshold concentration of voreloxin of 1 of more for 20 hours or more per week. At the maximum tolerated dose, the weekly Voreloxin (formerly SNS-595, Sunesis Pharmaschedule allowed for more time above the threshold ceuticals) is a novel first-in-class naphthyridine anathan the twice-weekly schedule allowed. Therefore, logue, a subclass of quinolones not previously used this schedule was chosen for additional development in cancer treatment. It has a specific, saturable interof voreloxin as a single agent. Voreloxin exhibited action with DNA, and it inhibits topo-isomerase II, linear pharmacokinetics with an approximate half-life resulting in replication-dependent, site-selective, douof 24 hours. ble-stranded DNA damage; irreversible G2 arrest; A dose-escalation study of voreloxin, in combinaand rapid apoptosis. Voreloxin is not a substrate for tion with continuous infusion of cytarabine liposome P-glycoprotein and is not p53 family member– Mar vin M. injection (Depo-Cyt, Enzon), is ongoing in patients with dependent; it is thus able to evade common drugGoldenberg, resistance mechanisms. This may contribute to the PhD, RPh, MS relapsed or refractor y AML. Preclinical studies indicated enhanced activity of voreloxin and cytarabine agent’s activity observed in anthracycline-resistant in combination. Voreloxin was given via a short intravenous patients. It also has a low potential for cytochrome P450– (IV) infusion (within 10 minutes) on the first and fourth days mediated drug–drug interactions. along with cytarabine 400 mg/m2 per day by continuous IV Voreloxin is in phase 1 and 2 clinical trials of acute myeloid leukemia (AML) and ovarian cancer, with positive clinical infusion for five days. The dosing regimen was chosen to allow responses being shown in these indications as well as in non– for adequate time above the threshold for voreloxin with small-cell lung cancer (NSCLC) and small-cell lung cancer. cytarabine to maximize the potential for a synergistic interIn a phase 1 dose-escalation study as a single agent in action that had been observed in preclinical models. patients with relapsed or refractory acute leukemia, voreloxin Primary objectives were to determine the safety and pharwas administered either weekly for three doses on days 1, 8, macokinetics of voreloxin. Secondary objectives were the preand 15 or twice weekly for four doses on days 1, 4, 8, and 11. liminary assessment of anti-leukemic responses and pharmaAt doses of 50 mg/m2 or above weekly or at doses of 40 mg/m2 codynamics markers. Voreloxin in doses of 10, 20, 34, 50, and 70 mg/m2 was given as slow IV-pushes within 10 minutes. twice weekly, clinical responses consisted of a reduction in bone marrow blasts or complete remission. Complete remissions have been observed with 20, 34, and The maximum tolerated doses were 72 mg/m2 weekly and 50 mg/m2, but it is too early to evaluate the 70-mg/m2 dose. 40 mg/m2 twice weekly. The dose-limiting toxicity in both Thus, voreloxin pharmacokinetic parameters appear to be unaffected by cytarabine. Common adverse effects included schedules was oral mucositis. Clinical responses to treatment febrile neutropenia and stomatitis. (including complete remission, complete remission without Because voreloxin as a single agent produced clinically posplatelet recover y, or complete remission with incomplete itive responses in older AML patients, a larger phase 2 study recovery of hematopoietic elements) were observed in patients of newly diagnosed de novo or secondary AML in patients 60 with relapsed or refractory AML who were both older and years of age and older is in progress with the weekly schedyounger than 60 years of age. ule at a dose of 72 mg/m2. The primary endpoints were clinical remission and partial clinical remission. • Gail J. Roboz, Cornell Medical School, New York, N.Y. The author is President of Pharmaceutical and Scientific Services at Marvin M. Goldenberg, LLC, in Westfield, New Jersey. His e-mail address is marvinmgoldenberg@verizon.net. Voreloxin for Acute Myelogenous Leukemia 712 P&T® • December 2008 • Vol. 33 No. 12

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Pharmacy & Therapeutics - December 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Interpreting Estimates of Treatment Effects Chemotherapy Foundation Symposium XXVI: Innovative Cancer Therapy for Tomorrow Third Annual Onmark National Payor/Provider Forum Fourth Annual Ophthalmic Drug Development and Delivery Summit Classification and Pharmacological Management Of Obesity CE Test and Forms Season’s Greetings: Thanks to Our Readers and Reviewers

Pharmacy & Therapeutics - December 2008

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