Shifting Shifting the treatment paradigm

Winship lung cancer researchers are aggressively pursuing the nation’s number one cancer killer, pushing the program to the front – and hoping to push the disease aside.

Small cell lung cancer has long been one of the most difficult cancers to treat, in part because it is usually diagnosed in an advanced stage and in part because it is so aggressive, outdistancing the therapies used to treat it and spreading to other organs almost vengefully. The disease typically responds to chemotherapy with or without radiation in a majority of the patients but often returns much more aggressively, frequently after a short remission.

“It is a tragic disappointment when the cancer returns,” says Taofeek Owonikoko, MD, PhD, “The options for retreatment are often limited, and the chances of a durable response are not great.”

Owonikoko is one of many Winship Cancer Institute lung cancer researchers helping to shift the national treatment paradigm for lung cancer, the nation’s number one cancer killer. He just opened a Phase II clinical trial in which he will be testing the effectiveness of arsenic trioxide, a drug typically used to treat leukemia, for patients who fail standard treatment for small cell lung cancer. His trial, for which he hopes to accrue 35 patients, also has another important goal – to gather tissue samples from patients to better understand the biology of this form of lung cancer.

Winship is supporting Owonikoko’s trial, and he also has received a Winship pilot grant from the support received from the Kennedy Foundation.

Arsenic trioxide is typically used to treat a type of leukemia called acute promyelocytic leukemia, or APL, Owonikoko explains, and not lung cancer. Owonikoko says he has come to believe that small cell lung cancer behaves somewhat like hematologic malignancies such as leukemia in that it responds well initially to treatment only to become resistant to further treatment.

However, evidence from lab work showing the potential benefit of arsenic trioxide for small cell lung cancer provided the strongest impetus to study arsenic trioxide in small cell lung cancer patients, Owonikoko says.

As for procuring tissue samples, Owonikoko says it is imperative to collect more tissue samples from lung cancer patients.

“There is often insufficient tissue from small cell lung cancer patients for testing in the lab,” explains Owonikoko. Given what researchers know about other cancers, Owonikoko and other lung cancer researchers believe that small cell lung cancers may not be a single type of disease at the genetic level, even though most all are caused by cigarette smoke and are currently treated the same way. Obtaining tissue samples from patients for extensive testing will provide an opportunity for the researchers to see whether there are subtle or significant differences in small cell lung cancer genomics from patient to patient and whether these differences may explain how and why patients might respond to different therapies.

Suresh Ramalingam, above, and Taofeek Owonikoko , right, are leading trials to advance treatment of lung cancer. Ramalingam recently has been named chair of the thoracic malignancies committee of the Eastern Cooperative Oncology Group, one of the largest clinical cancer research groups in the country.

“Once we get the biopsy, we would take the tumor specimen to the lab and grow it in laboratory animals and thereby establish a sort of small cell tumor bank that we can always go back to for detailed testing,” Owonikoko says. The goal would be to obtain tissue from about 20 patients. “That would be very, very useful,” he says.

The clinical study drug will be provided free to patients, and the treatment duration will be a year if the patient is benefiting from treatment. Because the trial will allow Owonikoko and team to study not only the effect of arsenic trioxide on patients but also create a great opportunity to study the tumor tissue, Owonikoko says the study is “getting the absolute bang for the buck.”

In another effort to define a new treatment paradigm, Winship’s Suresh Ramalingam, MD, director of the division of medical oncology, is chairing a Phase III trial of the Eastern Cooperative Oncology Group (ECOG) that is studying the optimal maintenance strategy for patients with advanced non-small cell lung cancer (NSCLC) who received bevacizumab as part of their first-line therapy. This is important because most patients diagnosed with NSCLC have advanced disease, and maintenance therapy has emerged as an option for those patients who benefited from firstline combination chemotherapy. This trial will enroll about 1,300 patients with advanced stage nonsquamous non-small cell lung cancer. They will receive four cycles of carboplatin, paclitaxel and bevacizumab. Those with a response or stable disease will be randomized to treatment with bevacizumab, pemetrexed, or a combination of the two agents.

“This study illustrates the important role played by Winship researchers in defining new standards of care for the treatment of lung cancer,” says Ramalingam. “Our lung cancer program has a major focus on developing individualized treatment options, and we are helping to change the treatment paradigm for lung cancer.”

“These trials are meant to further advance the treatment of lung cancer, and we at Winship are dedicated to being at the forefront,” says Ramalingam. “Though there have been improvements in treating lung cancer, we’re a long way from a cure for most patients. These trials are meant to move us in that direction.”