Virus Promising Against Colon Cancer

One injection of a genetically modified virus has demonstrated promise as a treatment for colorectal cancer that has metastasized to the liver, according to early study findings.

In a phase I study, researchers from Memorial Sloan-Kettering Cancer Center (MSKCC; New York, NY, USA) assessed an oncolytic herpes simplex virus (oHSV). These viruses selectively destroy cancer cells while sparing healthy tissue and are considered a promising new way to treat tumors. They have already been shown to be successful against chemotherapy-resistant tumors in preclinical studies.

The particular strain of virus studied by the investigators was NV1020, a weakened and modified form of herpes simplex virus type-1, the virus tied to cold sores. In the study, in 12 patients with colorectal adenocarcinoma that had metastisized to the liver and were shown to be resistant to first-line chemotherapy, the investigators evaluated increasing doses of the virus delivered in a single 10-minute arterial infusion. Treatment was followed by regional chemotherapy. Patients typically experienced mild-to-moderate adverse effects associated with the treatment, even though self-limiting serious effects suffered by three individuals were thought to be probably related to the virus. These events comprised a temporary increase of gamma-glutamyl transpeptidase--a sign of liver disease--12 hours after therapy in a patient with a history of hepatitis, an instance of gastroenteritis, and a case of mild leukocytosis thought to be caused by a respiratory infection.

None of the patients demonstrated any signs of disseminated herpes infection; the virus was found 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,” stated MSKCC Prof. Nancy Kemeny. "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 [carcinoembryonic antigen] reductions were seen in patients after virus administration and before regional therapy.”

To date, the overall average survival time of the 12 patients is 23 months and one patient is still alive at 30 months after therapy. "These results are very promising,” Prof. Kemeny remarked. "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 phase of the study will be to utilize multiple doses of the virus because preclinical data indicated that herpes oncolytic viruses function best when given in multiple doses. Prof. Hans Joachim Schmoll, of Martin-Luther-Universität Halle-Wittenberg (Germany), noted that locoregional chemotherapy is an excellent way to deliver 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. "These results represent the first time that an anti-tumor response has been seen after intra-arterial or systemic application of a tumor-killing virus. Therefore, the study is highly interesting and promising in terms of giving the basis for further trials with genetic-modified tumoricidal viral constructs.”

The study's findings were presented June 7, 2005, at the European Scientific & Educational Conference (ESEC) held in Budapest, Hungary.




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Memorial Sloan-Kettering Cancer Center