The American Association for Cancer Research announces a Call for Nominations for the 2009 AACR Outstanding Investigator Award for Breast Cancer Research, funded by Susan G. Komen for the Cure®.

The award recognizes a scientist who is no more than 50-years-old and who is conducting novel and significant work that has had or may have a far reaching impact on the etiology, detection, diagnosis, treatment or prevention of breast cancer. Such work may involve any discipline in biomedical research including basic, translational, clinical and epidemiological studies.

Last year, the inaugural award went to Douglas Easton, Ph.D., director of the Cancer Research UK Genetic Epidemiology Unit at the University of Cambridge in England, for his work with the BRCA1 and BRCA2 genes, which has provided important risk assessment tools in breast cancer.

The award winner will receive $10,000 and deliver a 25-minute lecture at the 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium, to be held December 9-13, 2009, in San Antonio, Texas.

- Deadline for nominations: May 15, 2009

Source
American Association for Cancer Research

CLEVELAND, May 11 — Adding a single oral dose of the novel antinausea drug casopitant mesylate to a standard antiemetic regimen significantly reduced chemotherapy-induced nausea and vomiting for five days in a multinational study.

• Explain to interested patients that this report describes results of a phase III trial of an investigational drug that is not FDA approved for clinical use.
• Explain to interested patients that a number of clinically available treatments have demonstrated efficacy for reducing nausea and vomiting associated with chemotherapy.

Compared to those receiving a placebo plus standard therapy (ondansetron (Zofran) and dexamethasone), patients receiving casopitant mesylate had no retching, vomiting, or need for a rescue medication in the first 120 hours after highly emetogenic chemotherapy, according to Steven M. Grunberg, M.D., a hematologist at the University of Vermont in Burlington, and colleagues.

Moreover, the benefit was significant and durable for both a single oral dose and a three-day intravenous/oral combination.

The results of the phase III trial appeared online in Lancet Oncology.

On May 20 the FDA’s Gastrointestinal Drugs Advisory Committee will review a new drug application for casopitant, which is being developed by GlaxoSmithKline under the brand name Rezonic.

The published results represent a modified intention-to-treat population.

The trial enrolled patients receiving cisplatin-based highly emetogenic chemotherapy at 77 clinical centers in 22 countries. Patients were enrolled from November 6, 2006 through October 9, 2007.

The average age of patients was the late 50s, and more than half had non-small cell lung cancer.

Patients randomized to casopitant, which is a neurokinin 1-receptor antagonist, received either a single oral dose of 150 mg (N=266) or a three-day intravenous dose (90 mg on day one) plus oral casopitant (50 mg on days two and three) on top of dexamethasone and ondansetron (N=269).

Results from both casopitant arms were compared with 265 controls.

In the single oral dose arm, 86% (228 of 266) of patients achieved complete response versus 66% of patients in the control group (P<0.0001). In the three-day, intravenous plus oral casopitant group, 80% of patients had a complete response (P=0.0004 versus controls), Dr. Grunberg and colleagues wrote.

“The effect of casopitant mesylate was maintained in the first four cycles of chemotherapy,” they reported. “Mean maximum nausea scores were 24.6 (SD 32.5) for the control group, 14.6 (23.9) for the single-dose oral casopitant group, and 16.8 (26.2) for the three-day intravenous and oral casopitant group.”

Neutropenia, febrile neutropenia, and dehydration were the most common serious adverse events in all groups, but the event rate was low (1% to 2%) and not measurably different among treatment groups.

They noted that “a higher proportion of patients who received cisplatin plus vinorelbine or cisplatin plus etoposide as part of their chemotherapeutic regimen in addition to casopitant mesylate had grade 4 neutropenia.

“Casopitant mesylate is a moderate inhibitor of CYP3A, and vinorelbine and etoposide are metabolized by CYP3A; thus, co-administration of these agents might have resulted in higher levels of the chemotherapeutic agents, which, in turn, might have produced a greater incidence of grade 4 neutropenia.”

The authors noted that while the trial was underway, several consensus guidelines for highly emetogenic chemotherapy were updated to include dexamethasone and aprepitant (Emend), an FDA-approved neurokinin 1-receptor antagonist marketed by Merck.

But they chose not to use aprepitant as part of the two-drug background therapy because “use of an NK1-receptor antagonist was not standard practice at the time of enrollment or the time of reporting.

The authors concluded that the data demonstrated both safety and efficacy for casopitant.

Moreover, they said that that to “our knowledge, this is the first report of a randomized phase III trial demonstrating the significant efficacy of a single oral dose of an NK1-receptor antagonist in the prevention of [chemotherapy- induced nausea and vomiting] for a full five days after [highly emetogenic chemotherapy].”

Dr. Grunberg disclosed that he is a consultant for GlaxoSmithKline, Merck, Helsinn, and Schering, owns stock in Schering and has received honoraria and research funds from Merck. Senior author Jørn Herrstedt, M.D., of Odense University Hospital in Odense, in Denmark said he is a consultant for GlaxoSmithKline, Helsinn, and Schering, and has received research funds from Merck. Five of the trial’s co-authors are employees of GlaxoSmithKline and own stock in the company. The study was funded by GlaxoSmithKline and, as sponsor, GlaxoSmithKline collaborated with Drs. Grunberg Herrstedt, M.D., on the trial design. The study data were collected by the trial’s clinical investigators and trial conduct was monitored by GlaxoSmithKline. The statistical analysis was done by GlaxoSmithKline, according to a predefined plan approved by Drs. Grunberg and Herrstedt, with periodic reports to a data safety monitoring board. The published manuscript “was developed with full author participation and assistance from a medical writer.”

Primary source: The Lancet Oncology

Source reference:

Grunberg, SM et al “Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial” Lancet 2009; DOI:10.1016/S1470-2045(09)70109-3.