Researchers at Ohio State University found that small doses of the drug suramin enhanced the effectiveness of standard chemotherapy drugs used to treat patients with advanced forms of lung cancer.
The 12 patients in the study were treated with a combination of suramin and the chemotherapy drugs paclitaxel and carboplatin. After following the patients for an average of nine months, researchers found that the tumors had not progressed in eight of the patients. In fact, tumors had shrunk in seven of the patients.
All of the patients in this study had stage IIIB or IV lung cancer - the most advanced stages of the disease -- when surgery or radiation is rarely an option. At these stages, the cancer has metastasized - or spread - to other parts of the body.
"Ninety percent of patients with metastatic lung cancer die within one year when treatment is not given," said Miguel Villalona, an assistant professor of internal medicine in the division of hematology and oncology at Ohio State. "With the best treatment available - chemotherapy - we can increase one-year survival rates to about 35 percent.
"We need to find something better than what we have for the treatment of lung cancer. Patients can't be cured of the cancer, but we may be able to prolong the length of life and improve its quality."
Villalona presented the findings in Miami Beach in October at the annual American Association for Cancer Research/National Cancer Institute/European Organization for Research and Treatment of Cancer International Conference. Villalona conducted this research with other Ohio State scientists, including Jessie L-S Au, Distinguished University Professor and Dorothy M. Davis Professor of Cancer Research at Ohio State's Comprehensive Cancer Center.
Cancer researchers have been looking at suramin as a possible cancer treatment for a couple of decades. A team of scientists from Ohio State last year published findings in the journal Proceedings of the National Academy of Science that suggested that giving suramin in low doses could be a potent anti-cancer therapy.
The patients in the current study were in the advanced stages of non-small cell lung cancer, the most common form of the disease, affecting about 75 percent of the patients with lung cancer. The non-small cell variety is typically associated with a history of smoking, passive smoking, or radon exposure, according to the NCI, and is usually treated by surgery or radiation therapy during the early stages of the disease. Chemotherapy is the treatment of choice for patients in the advanced stages of the disease.
Villalona and his colleagues wanted to figure out the proper dose of suramin to give to patients. Previous studies in mice had shown that the addition of suramin to standard chemotherapy treatment could eradicate lung cancer in some cases. In humans, high doses of suramin can in some instances halt tumor growth, but suramin at this level can be toxic. However, giving too little of the drug had no effect against cancer.
By the time the disease develops to stages III and IV, it has metastasized to lymph nodes surrounding the lungs or to other parts of the body. Researchers know that metastatic tumors produce high levels of a substance called fibroblastic growth factors (FGF) that may inhibit the ability of anticancer drugs to get to the tumor.
"We are still trying to explain how the inhibition of FGF by suramin leads to a decreased resistance of tumors to chemotherapy," Villalona said.
In the current study, Villalona and his colleagues found that they could tailor suramin dose levels to individual patients based on the patient's weight and gender. Very low doses of suramin given to patients just before the administration of paclitaxel and carboplatin halted FGF-induced resistance to the chemotherapy.
The researchers are continuing to monitor the patients in the study. Tumor growth had subsided in two-thirds of the patients (eight out of 12). These observations ranged from five to 12 months after starting the combined treatment regimen.
Adding suramin to the treatment regimen neither produced new side effects nor exacerbated the side effects commonly seen with paclitaxel/carboplatin. Side effects of paclitaxel/carboplatin treatment can include weakness, hair loss, low blood cell counts, numbness in the extremities and nausea and vomiting.
"While we are encouraged by these results, we've got a long way to go before suramin becomes a standard anti-cancer treatment," Villalona said. "This is the first hint that something good is happening. We will continue to follow the patients in the first phase of this trial."
The researchers are moving ahead with the second phase of the trial. They will look at two groups of lung cancer patients - those who haven't received chemotherapy, and those who have a history of chemo treatments.
This ongoing research is supported by grants from the National Cancer Institute.
Villalona and Au conducted the research with Ohio State researchers Gregory Otterson; Steven Kanter; Donn Young; Beth Fischer; Danny Chen; Sae Heum Song; Yange Zhang; Kenneth Chan; Michael Grever; and M Guillaume Wientjes; and Michael Straiko, previously employed by Ohio State's department of internal medicine.
Written by Holly Wagner, 614-292-8310; Wagner.235@osu.edu