Valganciclovir May Prolong Survival in CMV-Positive Glioblastoma

March 22, 2013

By Robert Saunders

NEW YORK (Reuters Health) Mar 22 - A pilot study suggests that patients with cytomegalovirus-positive glioblastoma multiforme may benefit from adjunctive valganciclovir - if it is continued for long enough.

"Tumor growth was hampered and survival was longer" with at least six months of valganciclovir treatment, researchers reported in the International Journal of Cancer online March 13.

They note that median survival after diagnosis of glioblastoma is less than 15 months, and new treatment strategies are "urgently needed."

"CMV is found frequently in an active form in tumors of different origins and in lymph node metastases, while normal cells surrounding tumors and metastases remain virus negative," Dr. Cecilia Soderberg-Naucler explained in an email to Reuters Health. "Lower virus levels in glioblastoma are associated with longer survival and targeting this virus may be an additional option to evaluate in cancer therapy for CMV-positive tumors."

Dr. Soderberg-Naucler, at the Karolinska Institute in Stockholm, Sweden, and colleagues studied 42 patients with CMV-positive glioblastoma who were randomized to receive valganciclovir (the prodrug of ganciclovir) or placebo in addition to standard therapy for six months.

There was a trend toward reduced tumor volumes in patients in the valganciclovir arm compared to the placebo arm, but the difference was not statistically significant, the team found. For example, at six months, the mean increase in tumor volume from baseline in the two groups was 3.31 cc versus 13.75 cc, but the p value was 0.212.

Also, the median overall survival estimates in the two arms were similar at 17.9 months and 17.4 months (p=0.430), respectively, according to the report.

In hindsight, the authors realized the study "did not have sufficient power to determine outcome differences in this small population of patients."

However, after the blinded phase of the trial concluded, all the patients could elect to receive valganciclovir on a compassionate basis. Seven of the patients originally assigned to valganciclovir continued on the treatment, and 12 of the placebo patients began taking valganciclovir.

"Patients who took valganciclovir after the study phase chose to do so when they were still blinded to the study drug; we did not know who had Valcyte for the first six months when they were prescribed the drug; it was the patients' own choice," Dr. Soderberg-Naucler said. "This is quite important when we analyze the data, otherwise we would have been biased to who received the drug."

A total of 22 patients received valganciclovir for at least six months. The investigators found that mean overall survival in this subset was 24.1 months, significantly longer than 13.1 months among those who received valganciclovir for a shorter duration or not at all (p<0.0001).

In fact, six of the 22 (27.3%) patients receiving at least six months of valganciclovir were alive at four years. "It is very rare that glioblastoma patients survive four years after their diagnosis," the authors comment.

Given these results, they conclude, "Long-term valganciclovir treatment may curb the rapid growth of glioblastoma, and the potential efficacy of prolonged treatment with valganciclovir in glioblastoma patients merits further investigation in a robust, well-powered clinical trial."

"We hope to obtain funding to initiate a larger randomized multi-center phase II/III trial to evaluate this concept further," Dr. Soderberg-Naucler added. "We believe that this option needs to be further evaluated for cancer patients suffering from CMV-positive tumors."

SOURCE: http://bit.ly/YKrC8k

Int J Cancer 2013.

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