Engineered virus shows early promise against colorectal carcinoma

Preliminary results of a phase I study showed that a single injection of a genetically engineered virus has shown promise as a treatment for patients with colorectal cancer that has spread to the liver.

Nancy Kemeny from Memorial Sloan-Kettering Cancer Center in New York, and colleagues tested an oncolytic Herpes simplex virus ( oHSV ).

These viruses selectively kill cancer cells while sparing normal tissue and are considered a promising new strategy to treat tumors. They have already been shown to be effective against chemotherapy-resistant cancers in preclinical studies.

The specific strain of virus investigated by Kemeny's team was NV1020, weakened and altered form of herpes simplex virus type-1.

In 12 patients with colorectal adenocarcinoma that had spread to the liver and proven resistant to first-line chemotherapy, the scientists tested increasing doses of NV1020 delivered via a single 10-minute arterial infusion. Treatment was followed by regional chemotherapy.

Patients in the study generally experienced mild or moderate adverse events associated with the treatment, the researchers found, although self-limiting serious adverse events experienced by three patients were considered possibly or probably related to NV1020.
These events comprised a temporary increase of gamma-glutamyl transpeptidase--a sign of liver disease--12 hours after treatment in a patient with a history of hepatitis, a case of gastroenteritis, and a case of mild leukocytosis considered due to a respiratory infection.

None of the patients showed any signs of disseminated herpes infection; the virus was detected in just one saliva sample and two blood samples from one asymptomatic patient who received the highest dose.

" Our primary aim in this study was to test the safety of the virus," Kemeny said. " We were pleased to see that the virus could be administered safely in the hepatic artery without significant effects on the normal liver function. We were also excited that CEA reductions were seen in patients after virus administration and before regional therapy."

The overall median survival time of the 12 patients was 23 months with one patient still alive at 30 months post therapy.

" These results are very promising," Kemeny says. " The median survival time we saw among our patients was higher than you might expect among this group of patients. However, all were treated with hepatic arterial therapy and systemic therapy after the virus therapy."

The next step for the investigators will be to use multiple doses of the virus since there are preclinical data to indicate that herpes oncolytic viruses work best when administered in multiple doses.

Commenting on the report, Hans Joachim Schmoll, of Martin-Luther-Universität Halle-Wittenberg in Germany, noted that locoregional chemotherapy is an excellent approach for delivering active drugs in metastatic colorectal cancer with liver metastases. "The application of the tumoricidal virus by the arterial route could be of high interest since higher viral load will be delivered to the liver metastases," he said.

Source: 2nd ESMO Scientific & Educational Conference, 2005



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