ORIGINAL ARTICLE
Efficacy of Capecitabine and Temozolomide Combination in Well-Differentiated Neuroendocrine Tumors Jordan Experience Salah Abbasi, MD,* Amneh Kashashna, RN,† and Hamzeh Albaba, MD* Objectives: Options for the treatment of well-differentiated neuroendocrine tumors (NETs) are limited. We evaluated the efficacy of capecitabine and temozolomide combination in patients from Jordan. Methods: A retrospective review was conducted of 21 patients with metastatic well-differentiated NETs who failed somatostatin analogues and chemotherapy. Patients received capecitabine and temozolomide regimen every 28 days, and evaluation was done every 2 cycles. Results: Twelve patients (57%) achieved partial response, and 5 (23%) achieved stable disease. Median progression-free survival was 16.5 months (range, 14.8–18 months). Of the 7 carcinoid tumors, 2 had partial response, and 2 had stable disease. There were no grade 4 toxicities or treatmentrelated deaths. Conclusions: Capecitabine and temozolomide regimen is an effective and well-tolerated salvage option for well-differentiated NETs. Key Words: capecitabine, temozolomide, neuroendocrine tumors (Pancreas 2014;43: 1303–1305)
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euroendocrine tumors (NETs) are a heterogeneous group of tumors that are characterized by their ability to secrete peptides resulting in distinctive hormonal syndromes. The NETs are rare, accounting for 1% to 2% of all malignancies, and recent epidemiological studies have observed increased incidence.1 The NETs are classified into the fast-growing, poorly differentiated tumors, with Ki-67 rate of more than 20%, and slowgrowing, well-differentiated to moderately differentiated NETs with Ki-67 rate of less than 20%.2 The well-differentiated NETs (WD-NETs) can be subclassified into 2 general categories: carcinoid tumors and pancreatic NETs. Carcinoid tumors can be associated with the secretion of serotonin and vasoactive substances resulting in the carcinoid syndrome. Syndromes associated with the hormone-secreting pancreatic NETs include, insulinoma, glucagonoma, vasoactive intestinal peptide-oma, and gastrinoma. Such symptoms frequently can be treated effectively with somatostatin analogues.3 In contrast to poorly differentiated NETs, which are more responsive to platinum-based chemotherapies, the WD-NETs, especially carcinoids, lack effective cytoreductive regimens in the metastatic setting. In the phase III PROMID trial, WD-NETs treated with Sandostatin LAR had an overall response rate (ORR) of less than 5%, stable disease (SD) rate of 66.7%, and progression-free survival (PFS) of 14.3 months.4 Results of chemotherapy had been more disappointing. Recent studies using streptozocin with 5-FU or doxorubicin have shown RRs of 6% to 16%,5,6 with substantial grades 3 and 4 toxicities and low PFS rates. From the Departments of *Oncology and †Nursing, King Hussein Cancer Center, Amman, Jordan. Received for publication October 5, 2013; accepted April 9, 2014. Reprints: Salah Abbasi, MD, Department of Oncology, 6th floor, King Hussein Cancer Center, Amman 11941, Jordan (e‐mail: [email protected]). The authors declare no conflict of interest. Copyright © 2014 by Lippincott Williams & Wilkins
Pancreas • Volume 43, Number 8, November 2014
The use of targeted therapies such as the tyrosine kinase inhibitor (sunitinib) and the mammalian target of rapamycin inhibitor (everolimus) has shown promising activities in pancreatic WDNETs. The PFS ranges from 11 to 11.4 months, respectively, versus 4.6 to 5.5 months with placebo. Although SD rate was high with both agents, the RRs were low (
Efficacy of Capecitabine and Temozolomide Combination in Well-Differentiated Neuroendocrine Tumors Jordan Experience Salah Abbasi, MD,* Amneh Kashashna, RN,† and Hamzeh Albaba, MD* Objectives: Options for the treatment of well-differentiated neuroendocrine tumors (NETs) are limited. We evaluated the efficacy of capecitabine and temozolomide combination in patients from Jordan. Methods: A retrospective review was conducted of 21 patients with metastatic well-differentiated NETs who failed somatostatin analogues and chemotherapy. Patients received capecitabine and temozolomide regimen every 28 days, and evaluation was done every 2 cycles. Results: Twelve patients (57%) achieved partial response, and 5 (23%) achieved stable disease. Median progression-free survival was 16.5 months (range, 14.8–18 months). Of the 7 carcinoid tumors, 2 had partial response, and 2 had stable disease. There were no grade 4 toxicities or treatmentrelated deaths. Conclusions: Capecitabine and temozolomide regimen is an effective and well-tolerated salvage option for well-differentiated NETs. Key Words: capecitabine, temozolomide, neuroendocrine tumors (Pancreas 2014;43: 1303–1305)
N
euroendocrine tumors (NETs) are a heterogeneous group of tumors that are characterized by their ability to secrete peptides resulting in distinctive hormonal syndromes. The NETs are rare, accounting for 1% to 2% of all malignancies, and recent epidemiological studies have observed increased incidence.1 The NETs are classified into the fast-growing, poorly differentiated tumors, with Ki-67 rate of more than 20%, and slowgrowing, well-differentiated to moderately differentiated NETs with Ki-67 rate of less than 20%.2 The well-differentiated NETs (WD-NETs) can be subclassified into 2 general categories: carcinoid tumors and pancreatic NETs. Carcinoid tumors can be associated with the secretion of serotonin and vasoactive substances resulting in the carcinoid syndrome. Syndromes associated with the hormone-secreting pancreatic NETs include, insulinoma, glucagonoma, vasoactive intestinal peptide-oma, and gastrinoma. Such symptoms frequently can be treated effectively with somatostatin analogues.3 In contrast to poorly differentiated NETs, which are more responsive to platinum-based chemotherapies, the WD-NETs, especially carcinoids, lack effective cytoreductive regimens in the metastatic setting. In the phase III PROMID trial, WD-NETs treated with Sandostatin LAR had an overall response rate (ORR) of less than 5%, stable disease (SD) rate of 66.7%, and progression-free survival (PFS) of 14.3 months.4 Results of chemotherapy had been more disappointing. Recent studies using streptozocin with 5-FU or doxorubicin have shown RRs of 6% to 16%,5,6 with substantial grades 3 and 4 toxicities and low PFS rates. From the Departments of *Oncology and †Nursing, King Hussein Cancer Center, Amman, Jordan. Received for publication October 5, 2013; accepted April 9, 2014. Reprints: Salah Abbasi, MD, Department of Oncology, 6th floor, King Hussein Cancer Center, Amman 11941, Jordan (e‐mail: [email protected]). The authors declare no conflict of interest. Copyright © 2014 by Lippincott Williams & Wilkins
Pancreas • Volume 43, Number 8, November 2014
The use of targeted therapies such as the tyrosine kinase inhibitor (sunitinib) and the mammalian target of rapamycin inhibitor (everolimus) has shown promising activities in pancreatic WDNETs. The PFS ranges from 11 to 11.4 months, respectively, versus 4.6 to 5.5 months with placebo. Although SD rate was high with both agents, the RRs were low (
