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Ranpirnase (Onconase) and Mesothelioma

Ranpirnase, sometimes called Onconase, is a drug that has shown some success in treating patients with malignant mesothelioma. This is a newer drug, and has not yet been approved by the Food and Drug Administration (FDA) to treat the cancer. However, the drug is still being used in clinical trials for mesothelioma in combination therapy treatments, as well as for a number of other conditions and diseases, ranging from Ebola to HPV. Ranpirnase has shown promise in treating several conditions to date, and recent studies using it alongside other drugs have shown antitumor activity in some malignant mesothelioma patients.

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How Ranpirnase Is Used to Treat Mesothelioma

According to the drug’s developer, the Alfacell Corporation, Onconase prevents cancer cells from synthesizing proteins and reproducing. By breaking down a cancer cell’s RNA, ranpirnase is thought to prevent tumor growth by disrupting a cancer cell’s ability to replicate, causing the cell to die.

Most anti-cancer treatments either target a cancer cell’s DNA or the proteins they use for regeneration and other activities. Ranpirnase is different in that it targets a cancer cell’s RNA, which serves as a connection between a cell’s DNA and protein. When ranpirnase is injected into a patient’s body, the drug attaches itself to cancer cells. Eventually, it breaks into the cell and destroys its tRNA, a type of RNA molecule that translates a code to a protein. Once this damage occurs, the cell enters a death process called apoptosis.

During early clinical trials using ranpirnase to treat patients with malignant mesothelioma, the drug proved capable of killing tumor cells both alone and in combination with other chemotherapy drugs, like cisplatin. Ranpirnase also found some success as a combination therapy when used with doxorubicin, another chemotherapy drug. A 2008 study noted that the combination therapy was a better option than doxorubicin alone and could potentially serve as a second-line treatment for mesothelioma patients who did not respond to first-line options.

Possible Side Effects of Ranpirnase

In clinical trials performed using a combination of ranpirnase and doxorubicin, the cytotoxin didn’t ultimately change the severity or number of side effects a patient faced compared to receiving doxorubicin alone. Among those side effects, most commonly seen were nausea, hair loss and fatigue.

In other testing, researchers suggested that ranpirnase could be a suitable drug for killing mesothelioma cells because it has very few side effects. According to a 2006 study, ranpirnase could be given to mesothelioma patients as a single agent through an IV on a weekly basis with minimal side effects. Further phase 3b studies were less successful though, and did not prove to be as effective as the standard of care patients receive, which is currently a combination of pemetrexed and a platinum-based drug like cisplatin. The study also resulted in several dangerous side effects for patients.

Reported Ranpirnase Side Effects
  • Allergic reactions
  • Kidney problems
  • Swelling in the lower hands and feet

Further studies will need to be conducted to fully understand the role ranpirnase may play in treating mesothelioma patients. The drug is currently part of a randomized phase 3 study to determine whether a combination of ranpiranse and doxorubicin is more effective at treating the disease compared to using doxorubicin alone.

Studies Associated with Ranpirnase

Currently, ranpirnase is showing some promise when used as part of a combination mesothelioma treatment. In pre-clinical trials and in previous studies, certain drugs have increased the cytotoxic effects of ranpirnase including cisplatin, doxorubicin and tamoxifen.

In phase 3 studies testing the efficacy of ranpirnase compared to doxorubicin, patients who were given ranpirnase survived 11.6 months on average, compared to 9.6 months for patients treated with doxorubicin alone. A second phase 3 clinical trial comparing a combination of ranpirnase and doxorubicin with a treatment plan using doxorubicin alone produced similar results. Patients receiving the combination therapy survived 12 months, compared to 10 months for those getting the single drug. Survival rates also favored the combination therapy as 47% of patients were alive at least one year after treatment, while doxorubicin achieved a 1-year survival rate of 36%.

While further research is needed to determine whether or not ranpirnase is an effective treatment for mesothelioma, other studies combining the drug with different proteins have shown a fair amount of success in general testing. For example, Onconase was recently combined with transferrin, a protein that transports iron throughout the body, and receptor proteins to study their reaction to cancer cells in E. Coli samples. By adding the receptors to the drug, researchers found Onconase could more effectively target tumors. Researchers believe that with more testing, Onconase combined with transferrin and receptors could eventually serve as a targeted antitumor treatment.

Author: Linda Molinari

Editor in Chief, Mesothelioma Cancer Alliance

Linda Molinari

Reviewer: Annette Charlevois

Patient Support Coordinator

Annette Charlevois

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U.S. Food and Drug Administration. Ranpirnase.

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