Combination of generic drugs shows promise
Exciting news for carcinoid/NETs patients of all types emerged at the February Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology in San Francisco.
…the drug combination faces two challenges.
Robert Lance Fine (MD) announced interim results of a Phase II study of a combination of Capecitabine (Xeloda) and Temozolomide (Temodar) he called ‘remarkable” in an interview with Medscape Medical News. “I was shocked by them,” the doctor from the New York Presbyterian Hospital Columbia University Medical Center told Medscape.
Results trump chemotherapy response
The drug combination, referred to as CAPTEM, combines two generic oral drugs that have been used in treating other cancers.
‘I was shocked…’ –Robert Fine, MD
The normal response to chemotherapy in carcinoids, which make up about 55 percent of all neuroendocrine tumors is 0-4 percent. The CAPTEM combination resulted in a positive response in 95 percent of the 12 patients with carcinoid tumors: 45 percent saw a reduction in tumor size, while 52 percent saw stable disease as a result.
Effective for several forms, Fine says
Including three other forms of NETs, including pancreatic NETs–which makes up 35 percent of all diagnosed neuroendocrine cancers–the overall response rate showed 45 percent with tumors reduced in size and 50 percent with stable disease. The total number of patients in the study was 28.
…45 percent saw a reduction in tumor size…
But the most dramatic results were on pituitary NETs. The combination was tried on three end-stage patients, two of whom were on respirators. Two patients have complete remission under the regimen. The third saw a 75 percent reduction in tumor-size. One of those patients, who had been told he had six months to live is still alive eight years later. A fourth patient had stable disease for five years.
Low toxicity and mild side effects
Another good piece of news was the low toxicity and mild side effects of the treatment combination. Fine said there were, “No hospitalizations or treatment related deaths,” during the study.
…the most dramatic results were on pituitary NETs.
“The regimen was effective even in patients with tumors that hadn’t responded to any other standard treatment, including chemotherapy, high dose Octreotide, small molecule inhibitors, radiation or therapy,” Fine said.
Comparison with other therapies favorable
Octreotide, the current standard of care for treating NETs, reduces tumor size about
six percent of the time. It results in progression free disease 30-40 percent of the time.
No hospitalizations or treatment related deaths… –Fine
Sunitinib (Sutent), which is currently only approved for pancreatic NETs, results in tumor reduction about ten percent of the time and stable disease about 60 percent of the time. It is currently in trials for carcinoid tumors.
One drug helps the other
The CAPTEM regimen uses the two drugs sequentially over a 28 day period. The Capecitibine depletes thymidine stores in the cells. That improves the cell-killing ability of the Temozolomide.
Octreotide…reduces tumor size about six percent of the time.
While the study is not yet finished, so far carcinoid patients have experienced median Progression Free Survivor rate of over 31 months. That number is still growing as the study is not yet finished.
Challenges remain
Full exploitation of the drug combination faces two challenges. First, because the drugs are now generic, drug companies have little interest in funding trials. Second, because the drugs are oral, rather than intravenous, Medicare does not provide very good reimbursement–and some insurance companies provide none at all.
…the study is not yet finished…
Despite these two strikes against it, CAPTEM is now the subject of an Eastern Cooperative Oncology Group trial in patients with pancreatic NETs. That study is larger–though still small–and randomized.
Editor’s note: This story draws on articles from OncLive, Medscape Medical News, and MedPageToday.
