The NSABP's decision to continue the trial was based on a recommendation from an independent Data Monitoring Committee (DMC) after a planned interim analysis.

The study of 2,710 patients is being conducted by the NSABP and is sponsored by the National Cancer Institute. The independent DMC is responsible for monitoring patient safety and efficacy, as well as recommending whether to stop or continue the trial. Genentech anticipates final results from NSABP C-08 in mid-2009.

NSABP C-08 is a randomized, multi-center Phase III study designed to evaluate the effect of FOLFOX (5-fluorouracil, leucovorin and oxaliplatin) chemotherapy with or without Avastin on disease-free survival in patients with resected Stage II or III adenocarcinoma of the colon. The trial is being conducted primarily in the United States. Patients enrolled in the two-arm study were randomized after surgery to receive either FOLFOX alone for six months or Avastin in combination with FOLFOX for six months followed by an additional six months of Avastin monotherapy. Overall survival is a secondary endpoint of the study.

At the American Society of Clinical Oncology 2008 annual meeting, Allegra et al. presented interim safety data from NSABP C-08 that showed no new or unexpected safety events in the Avastin arm. The incidence of non-cancer-related deaths was similar between the treatment arms and no significant increases in gastrointestinal (GI) perforation, hemorrhage, arterial or venous thrombotic events or deaths were observed in the Avastin arm. The analysis showed events that occurred more often in the Avastin plus chemotherapy arm included Grade 3 or greater hypertension (12.7 percent vs. 1.8 percent), wound healing complications (1.7 percent vs. 0.3 percent), pain (6.9 percent vs. 3.4 percent), proteinuria (0.9 percent vs. 0.2 percent), and Grade 2 or greater sensory neuropathy (49.4 percent vs. 43.2 percent).

gene

Bargmann found a worm with a specific mutation to the gcy-28 gene that altered the neuron under study, known as AWC-on, causing naive worms to flee from butanone. By systematically examining worms with different mutations affecting the AWC-on neuron as well as other neurons that might impact the worm's reaction to butanone, the researchers were able to confirm that a specific chemical signaling pathway is used by the AWC-on neuron to direct the worms' movement either toward or away from the odor. These as well as other tests, including the use of a laser to destroy specific neurons, demonstrated that a single sensory neuron, responding to stimuli from both inside and outside the worm, could change the worm's preferences and behaviors.

The finding defies the pure "labeled-line" theory of sensation, which holds that sensory neurons are specialized to follow one path to one behavior.

Although there are vast differences in the nervous systems of worms and mammals, Bargmann believes that her findings may also be true of olfactory perception in higher mammals such as humans. "If what we're seeing in the worms is the ability of sensory cells to respond to internal needs, and to multitask profoundly, I bet the mammalian brain can do that as well," she says.

Neuron 59(6): 959-971 (September 25, 2008)

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