Meeting News CoveragePerspective

Chemotherapy combination shows promise as second-line therapy for neuroendocrine tumors

The combination of capecitabine plus temozolomide demonstrated efficacy in patients with well- to moderately differentiated neuroendocrine tumors resistant to octreotide, according to phase 2 study results presented at the 2014 Gastrointestinal Cancers Symposium.

“Well-differentiated neuroendocrine tumors tend to be chemotherapy resistant, with response rates lower than 10%, and carcinoid subgroup response rates lower than 3%,” Robert Fine, MD, associate professor of medicine at New York Presbyterian Hospital-Columbia University Medical Center, said during a press conference. “Sandostatin has been the standard of care, and now that...[the mTOR inhibitor] everolimus (Afinitor, Zortress; Novartis) and the [tyrosine kinase inhibitor] sunitinib (Sutent, Pfizer) have entered the stage, they have response rates of less than 10%, with stable disease rates of 60%. Thus, there is a great need for new treatments in well-differentiated neuroendocrine tumors.”

Fine and colleagues evaluated data from 28 patients who experienced disease progression with 60 mg octreotide (Sandostatin LAR, Novartis). Patients were younger than 80 years and had an ECOG performance status from 0 to 2.

Among the study population, 12 patients had carcinoid tumors, three had pituitary tumors, 11 had peripheral neuroectodermal tumors and two had medullary thyroid tumors.

Patients received 1,500 mg/m2 capecitabine on days 1 to 14 and 150 mg/m2 to 200 mg/m2 temozolomide on days 10 to 14, followed by 2 weeks off, in 28-day cycles.

The overall rate of response with the capecitabine plus temozolomide combination (CAPTEM) was 43%, and 11% of patients experienced a complete response.

Fifty-four percent of patients achieved stable disease, and 97% of patients demonstrated clinical benefit.

Among patients with carcinoid tumors, 41% demonstrated response.

The ongoing median PFS is more than 20 months, and the ongoing median OS is more than 25.3 months.

The most commonly observed grade 3 to grade 4 toxicities were lymphopenia (32%), hyperglycemia (15%), thrombocytopenia (3%) and diarrhea (3%). Researchers noted there were no treatment-related hospitalizations, opportunistic infections or deaths.

“In this study, we’re seeing patients who had been given 6 months to live who are still alive 8 years after starting CAPTEM,” Fine said in a press release. “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.”

For more information:

Fine RL. Abstract #179. Presented at: 2014 Gastrointestinal Cancers Symposium; Jan. 16-18, 2014; San Francisco.

Disclosure: Fine reports research funding from Merck.

The combination of capecitabine plus temozolomide demonstrated efficacy in patients with well- to moderately differentiated neuroendocrine tumors resistant to octreotide, according to phase 2 study results presented at the 2014 Gastrointestinal Cancers Symposium.

“Well-differentiated neuroendocrine tumors tend to be chemotherapy resistant, with response rates lower than 10%, and carcinoid subgroup response rates lower than 3%,” Robert Fine, MD, associate professor of medicine at New York Presbyterian Hospital-Columbia University Medical Center, said during a press conference. “Sandostatin has been the standard of care, and now that...[the mTOR inhibitor] everolimus (Afinitor, Zortress; Novartis) and the [tyrosine kinase inhibitor] sunitinib (Sutent, Pfizer) have entered the stage, they have response rates of less than 10%, with stable disease rates of 60%. Thus, there is a great need for new treatments in well-differentiated neuroendocrine tumors.”

Fine and colleagues evaluated data from 28 patients who experienced disease progression with 60 mg octreotide (Sandostatin LAR, Novartis). Patients were younger than 80 years and had an ECOG performance status from 0 to 2.

Among the study population, 12 patients had carcinoid tumors, three had pituitary tumors, 11 had peripheral neuroectodermal tumors and two had medullary thyroid tumors.

Patients received 1,500 mg/m2 capecitabine on days 1 to 14 and 150 mg/m2 to 200 mg/m2 temozolomide on days 10 to 14, followed by 2 weeks off, in 28-day cycles.

The overall rate of response with the capecitabine plus temozolomide combination (CAPTEM) was 43%, and 11% of patients experienced a complete response.

Fifty-four percent of patients achieved stable disease, and 97% of patients demonstrated clinical benefit.

Among patients with carcinoid tumors, 41% demonstrated response.

The ongoing median PFS is more than 20 months, and the ongoing median OS is more than 25.3 months.

The most commonly observed grade 3 to grade 4 toxicities were lymphopenia (32%), hyperglycemia (15%), thrombocytopenia (3%) and diarrhea (3%). Researchers noted there were no treatment-related hospitalizations, opportunistic infections or deaths.

“In this study, we’re seeing patients who had been given 6 months to live who are still alive 8 years after starting CAPTEM,” Fine said in a press release. “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.”

For more information:

Fine RL. Abstract #179. Presented at: 2014 Gastrointestinal Cancers Symposium; Jan. 16-18, 2014; San Francisco.

Disclosure: Fine reports research funding from Merck.

    Perspective

    This study is of interest — although it is small, and not randomized — because the CAPTEM combination resulted in tumor responses in neuroendocrine tumors that are typically resistant to chemotherapy. Five of the 12 carcinoid patients responded. This regimen of CAPTEM vs. temozolomide is under study now in a cooperative group trial for patients with pancreatic neuroendocrine cancer.

    • Smitha Krishnamurthi, MD
    • Associate professor of medicine University Hospitals Case Medical Center Case Western Reserve University

    Disclosures: Krishnamurthi reports honoraria and research funding from Nektar and UpToDate.

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