FDA approves new therapy for initial treatment of soft tissue sarcoma

In continuation of my update on Doxorubicin

The U.S. Food and Drug Administration today granted accelerated approval to Lartruvo (olaratumab) with doxorubicin to treat adults with certain types of soft tissue sarcoma (STS), which are cancers that develop in muscles, fat, tendons or other soft tissues. Lartruvo is approved for use with the FDA-approved chemotherapy drug doxorubicin for the treatment of patients with STS who cannot be cured with radiation or surgery and who have a type of STS for which an anthracycline (chemotherapy) is an appropriate treatment.

"For these patients, Lartruvo, added to doxorubicin, provides a new treatment option," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research and acting director of the FDA's Oncology Center of Excellence. "This is the first new therapy approved by the FDA for the initial treatment of soft tissue sarcoma since doxorubicin's approval more than 40 years ago."

The National Cancer Institute estimates that 12,310 new cases of STS and nearly 5,000 deaths are likely to occur from the disease in 2016. The most common treatment for STS that cannot be removed by surgery is treatment with doxorubicin alone or with other drugs. STS includes a wide variety of tumors arising in the muscle, fat, blood vessels, nerves, tendons or the lining of the joints.

Lartruvo is a platelet-derived growth factor (PDGF) receptor-alpha blocking antibody. When stimulated, PDGF receptors cause tumor growth. Lartruvo works by blocking these receptors, which may help slow or stop tumor growth.

The safety and efficacy of Lartruvo were studied in a randomized clinical trial involving 133 patients with more than 25 different subtypes of metastatic STS. Patients received either Lartruvo with doxorubicin or doxorubicin alone. This trial measured the length of time patients lived after treatment (overall survival), the length of time tumors did not grow after treatment (progression-free survival) and the percentage of patients who experienced shrinkage of their tumors (overall response rate). Patients in this trial who received Lartruvo with doxorubicin had a statistically significant improvement in overall survival: the median survival was 26.5 months compared to 14.7 months for patients who received doxorubicin alone. Patients who received Lartruvo with doxorubicin had a median progression-free survival of 8.2 months compared to 4.4 months for patients who received doxorubicin alone. Tumor shrinkage was 18.2 percent for patients who received Lartruvo with doxorubicin and 7.5 percent for those who received doxorubicin alone.

Lartruvo has serious risks including infusion-related reactions and embryo-fetal harm. Infusion-related reactions include low blood pressure, fever, chills and rash. The most common side effects of treatment with Lartruvo are nausea, fatigue, low levels of white blood cells (neutropenia), musculoskeletal pain, inflammation of the mucous membranes (mucositis), hair loss (alopecia), vomiting, diarrhea, decreased appetite, abdominal pain, nerve damage (neuropathy) and headache.

The FDA granted the Lartruvo application fast track designation, breakthrough therapy designation and priority review status because preliminary clinical evidence indicated that it may offer a substantial improvement in effectiveness in the treatment of a serious or life-threatening disease or condition. The FDA is approving Lartruvo under the agency's accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease or condition based on clinical data showing the drug has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit. The sponsor is conducting a larger study, which is currently underway, to further explore the effectiveness of Lartruvo across the multiple subtypes of STS.

Lartruvo also received orphan drug designation, which provides incentives such as tax credits, user fee waivers and eligibility for exclusivity to assist and encourage the development of drugs intended to treat rare diseases.

Chemotherapy drug combined with cancer-killing virus may treat recurrent ovarian cancer

In continuation of my update on doxorubicin

In six out of 10 cases, ovarian cancer is diagnosed when the disease is advanced and five-year survival is only 27 percent. A new study suggests that a cancer-killing virus combined with a chemotherapy drug might safely and effectively treat advanced or recurrent forms of the disease.

Researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James), led the cell and animal study. Reporting in the journal Clinical Cancer Research, the researchers showed that the oncolytic virus called 34.5ENVE has significant antitumor activity against ovarian cancer on its own, and that its activity is even greater when combined with the chemotherapy drug doxorubicin in an animal model of disseminated peritoneal ovarian cancer.

"Our findings suggest that this could be a promising therapy, and we believe it should be further developed for the treatment of recurrent or refractory ovarian cancer in humans," says principal investigator Balveen Kaur, PhD, professor of neurological surgery and an OSUCCC - James researcher.

Among women treated for ovarian cancer whose tumors regress, 70 percent experience recurrence. The recurrent tumors are thought to develop from reserves of cancer stem-like cells that are chemotherapy-resistant and survive therapy. Consequently, recurrent tumors also tend to be resistant to primary chemotherapy regimens, and lethal.

The oncolytic herpes simplex virus 34.5ENVE is engineered to target cancer cells that overexpress the protein nestin and to inhibit the growth of blood vessels to tumors.

Chemotherapy drug combined with cancer-killing virus may treat recurrent ovarian cancer

Drug trio of rapamycin, sildenafil and doxorubicin improved effectiveness of cancer treatment, protected heart

Combining cancer medication with a drug for erectile dysfunction and one for heart transplants helped kill cancer cells and protected the heart from damage. For decades, doxorubicin has been a powerful anti-cancer treatment for various human cancers, including breast, ovarian, colon and prostate. But its use has been limited due to harmful, possibly irreversible effects on the heart.

In this study, using cell and animal models, researchers found that sildenafil alone or in combination with rapamycin (an immunosuppressant used to prevent post-transplant organ rejection) significantly improved the anti-cancer effects of doxorubicin while protecting the heart. The combination of all three medications showed the most powerful effect, researchers said.

"Because sildenafil and rapamycin are clinically approved drugs that both protect heart muscle, we thought that combining these drugs with doxorubicin would be a unique strategy to eliminate the cardiac side effects of doxorubicin while further improving its cancer-killing ability," said Rakesh Kukreja, Ph.D., study co-author and professor of internal medicine and cardiology, Virginia Commonwealth University (VCU) School of Medicine in Richmond.

"The drug combination led to a dramatic protection of heart muscle from apoptosis (cellular self-destruction) and, to a lesser extent, necrosis (cell death from disease)," said David E. Durrant, study lead author and Ph.D. candidate at the VCU School of Medicine. "We think this combination therapy may have excellent potential to move forward into clinical trials and eventually improve life expectancy of cancer patients."

Drug trio improved effectiveness of cancer treatment, protected heart