Further evidence of the potential of reovirus in cancer therapy

Last week we commented on a small study of the use of reovirus in the treatment of localized prostate cancer. A new study has now shown that the combination of reovirus injections and radiotherapy has significant activity in advanced forms of other cancers.

We should be clear that the new study, just published on line by Harrington et al. in Clinical Cancer Research, does not seem to have included any prostate cancer patients. It was based on data from 23 patients with other forms of solid tumor, including lung, colorectal, pancreatic, and ovarian cancers as well as malignant melanoma (a type of skin cancer). However, all of these patients had progressive forms of their disease and were no longer responsive to standard therapies for their particular type of cancer.

The primary objective of this study was to find out whether it was both possible and safe to combine intratumoral injections of Reolysin (RT3D) — an investigational formulation of reovirus — with radiotherapy to treat patients with advanced forms of cancer. To be eligible for the study, patients had to have measurable forms of cancer that could be expected to show some degree of response to palliative radiotherapy (i.e., therapy that was not expected to have any curative impact but would help to manage the patients symptoms). Although clinical responses to therapy were not one of the key endpoints of this trial, the research team was able to observe the way tumors responded to this combination therapy.

Patients were treated in two groups. The first set of patients received a total of 20 Gy of radiotherapy in five fractions along with two injections of RT3D. The second group of patients received a higher dose of radiation therapy (36 Gy in 12 fractions) along with two, four, or six doses of RT3D.

The results of the study are reported as follows:

  • No patient showed any sign of a dose-limiting toxicity.
  • The most common toxicities were all grade 2 or lower, and included pyrexia (fever), influenza-like symptoms, vomiting, asymptomatic lymphopenia, and neutropenia.
  • There was no increase in the predicted acute reaction to radiation therapy.
  • Studies of blood, urine, stool, and sputum were negative for viral shedding based on reverse transcriptase-PCR.
  • In the low-dose (20 Gy in five fractions) radiation group, 2/7 evaluable patients had a partial response and 5/7 had stable disease.
  • In the high-dose (36 Gy in 12 fractions) radiation group, 5/7 evaluable patients had a partial response and 2/7 had stable disease.

These data do imply that 9/23 patients treated (39.1 percent) were not evaluable with respect to clinical response, but the abstract of the paper does not give information about these 9 patients that would explain why they were not evaluable. According to a report in the Telegraph in the UK, “tumors shrank or stopped growing in every patient who underwent radiotherapy coupled with a new drug, Reolysin, which contains particles of reovirus,” and one patient “who was close to death with a serious form of spreading skin cancer was still alive 17 months later.” The first of these two statements seems to be at variance with the lack of information about evaluability of 9 patients. Indeed, according to a media release from Oncolytics Biotech, the Canadian company that is developing Reolysin, “All 14 patients considered evaluable for treatment response in this study had [stable disease] or better for a clinical benefit rate of 100%.”

Harrington and his colleagues conclude simply that, the “combination of intratumoral RT3D and radiotherapy was well tolerated. The favorable toxicity profile and lack of vector shedding means that this combination should be evaluated in newly diagnosed patients receiving radiotherapy with curative intent.”

It would appear as though localized and perhaps even locally advanced forms of prostate cancer might be appropriate conditions in which to investigate the combination of radiation with intratumoral reovirus injections. Obviously the decision as to how to proceed with the clinical development of Reolysin is a decision for Oncolytics Biotech — the developer of this therapy, but we shall continue to “watch this space” with interest.

2 Responses

  1. Need STAT therapy/clinical trial info for “small cell carcinoma of the prostate”, a rare variant, quickly lethal carcinoma.

  2. It is worth noting that on May 25, 2010, Oncolytics Biotech opened enrollment in a Phase III clinical trial examining the effectiveness and safety of Reolysin in combination with paclitaxel and carboplatin in patients with platinum-refractory head and neck cancers.

    This will tell us nothing about the value of Reolysin in prostate cancer, but it is still an interesting development.

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