SAN FRANCISCO—Combination capecitabine and temozolomide (CAPTEM) offers long-lasting neuroendocrine tumor control for patients whose tumors have not responded to standard high-dose octreotide therapy, reported authors of an interim phase 2 analysis at the 2014 Gastrointestinal Cancers Symposium.

5-fluorouracil (5-FU, similar to capecitabine) acts synergistically with temozolomide; oral 5-FU followed by CAPTEM administration dramatically improves the antitumor activity of temozolomide, by up to 400%, the investigators reported. Administering capecitabine first and then temozolomide maximized efficacy, they noted.

“In this study we’re seeing patients who had been given 6 months to live that are still alive 8 years after starting CAPTEM,” reported lead author Robert Fine, MD, associate professor of medicine at New York Presbyterian Hospital-Columbia University Medical Center in New York, NY. “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 surgery.”

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High response rates were seen even in carcinoid and pituitary tumors, types of neuroendocrine tumor that are notoriously chemoresistant.

The ongoing progression-free survival (PFS) exceeded 22.2 months, with a low rate of serious toxicities and no hospitalizations or treatment-related deaths, the authors reported. Median overall survival exceeded 25 months.

The researchers enrolled 28 patients with metastatic, well- or moderately differentiated neuroendocrine tumors. All patients were either ineligible for standard high-dose octreotide treatment, or had tumors that had progressed despite high-dose octreotide therapy, Dr. Fine said.

All participants were orally administered CAP 1,500 mg/m2, split into two doses per day, on days 1 to 14, then orally-administered TEM 150-200 mg/m2 split into two doses per day on days 10 to 14, followed by 2 weeks off in the 28 day cycle. Patients who had undergone previous chemotherapy or extensive radiation received a lower dose of TEM, the authors noted.

Tumor size decreased in 43% of patients overall, and tumor growth halted in another 54% of patients, compared to a typical response rate for chemotherapy of up to 4%, Dr. Fine noted.

“The most common [grade] 3/4 toxicities were lymphopenia (35%), hyperglycemia (6%, unlikely related), thrombocytopenia (3%), and diarrhea (3%),” Dr. Fine said. “No hospitalizations, opportunistic infections or deaths occurred from CAPTEM.”

Neuroendocrine tumors originate in hormone-producing cells and are slow-growing and typically resistant to chemotherapy. Up to 9,000 people are newly diagnosed with these tumors each year in the United States. Because these tumors are typically asymptomatic until they are quite large, neuroendocrine tumors are commonly diagnosed at advanced stages.

The team is now investigating CAPTEM combinations with platelet-derived growth factor pathway blockade agents. CAPTEM should also be tested clinically against brain tumors and melanoma, Dr. Fine said.

The 2014 Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Surgical Oncology (SSO).


  1. Fine RL, Gulati A, Tsushima D, et al. Abstract 179. Presented at: 2014 Gastrointestinal Cancers Symposium. Jan. 16-18, 2014; San Francisco.