Carmustine wafers help treat brain metastases, preserve function

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 - Cognitive trajectory of patients with brain metastases improved with surgery, carmustine wafers

Treatment with neurological resection and carmustine wafers (CW) improved the cognitive trajectory, particularly memory and executive function, of patients with brain metastases, according to a study published in the November issue of Cancer.

“The rising incidence of metastasis to the brain threatens to limit gains made by new systemic treatments,” wrote authors Steven Brem, MD, of the Moffitt Cancer Center, Tampa, Fla., and colleagues.

Single and ogliometastatic cancer to the brain are often acceptably treated by neurosurgical resection and whole-brain radiation therapy (WBRT). However, WBRT is known to produce a decline in neurocognitive function (NCF), so a shift in treatment has led to a replacement of WBRT with localized surgery.

Because the delivery of systemic drugs to the tumors in the brain is impeded, biodegradable carmustine polymer wafers have been developed to enhance drug delivery. The researchers thus designed a prospective, multicenter phase 2 study to determine if surgery and CW could preserve NCF and achieve local control (LC). WBRT was deferred.

NCF and LC were measured in 59 patients who underwent resection and received CW for a single (83 percent) or dominant (oligometastastic, two to three lesions) metastasis and received stereotactic radiosurgery for tiny nodules that were not treated with resection plus CW.

Preservation of NCF was defined as an improvement or a decline less than or equal to one standard deviation from baseline in three domains: memory, executive function, and fine motor skills. These were evaluated at two-month intervals.

The study’s results indicated that executive function and memory significantly improved throughout the one-year follow up. Preservation or improvement of NCF occurred in all three domains for 65 percent of patients at each of the two-month intervals. NCF declined in one patient.

The CW were well-tolerated, and any serious adverse events were reversible. Local recurrence was found in 28 percent of the patients at the one-year follow-up, which is superior to the rates found in previous studies of surgery without wafers.

Nine participants died during the 12-month follow-up period but only one patient died because of neurologic disease progression.

“The range of options for patients with brain metastases will be increased as the novel, pathway-specific, targeted agents are evaluated,” wrote the authors. “The preserved and often improved NCF observed using resection and local carmustine wafers, as well as the known pharmacokinetics of carmustine, suggest that this strategy can be used without injury to white matter fiber tracts that affect NCF.”