First‐line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas

Abstract

BACKGROUND Temozolomide is an active agent in metastatic pancreatic endocrine carcinomas. In vitro data indicate that the combination of capecitabine and temozolomide is synergistic for induction of apoptosis in neuroendocrine tumor cell lines. The authors retrospectively evaluated the efficacy of capecitabine and temozolomide in 30 patients with metastatic pancreatic endocrine carcinomas to assess response rate, progression free survival (PFS), and overall survival (OS). METHODS Patients with metastatic, well, or moderately differentiated pancreatic endocrine carcinomas who had not received prior systemic chemotherapy were treated with capecitabine (750 mg/m2 twice daily, days 1–14) and temozolomide (200 mg/m2 once daily, days 10–14) every 28 days. RESULTS Among 30 patients treated, 21 (70%) patients achieved an objective radiographic response. Median progression-free survival was 18 months. The rate of survival at two years was 92%. Only 4 patients (12%) experienced grade 3 or 4 adverse events. CONCLUSIONS The combination of capecitabine and temozolomide is associated with an exceptionally high and durable response rate in metastatic endocrine carcinomas of the pancreas. Clinical endpoints, including response rate, survival, and toxicity, are superior to those observed with streptozocin-based regimens

Cytotoxic chemotherapy for pancreatic neuroendocrine tumors

“…Temozolomide (Table 3) [22][23][24][25][26][27][28][29] Temozolomide is an oral alkylating agent that is used to treat glioblastoma and melanoma. Because the side-effects of temozolomide are mild and it is an oral drug, temozolomide chemotherapy is expected to be less stressful for patients, and several studies of combination therapies with other drugs have been conducted in addition to a study of temozolomide alone.…”

“…When used as a monotherapy, the response rate was 14%, the median PFS was 7 months, and the median survival time was 16 months [23]. While the results of temozolomide monotherapy were marginal, all the studies that have been conducted examining combination therapy with capecitabine have reported promising results with regard to the response rate, PFS, and survival time, and this combination, in particular, has attracted interest [24][25][26][27][28][29]. The Eastern Cooperative Oncology Group (ECOG) is currently conducting a NA not available, PFS progression-free survival Alkylating agents, including temozolomide, induce the methylation of the O 6 -position of guanine, which results in DNA mismatching and ultimately results in apoptosis and tumor cell death.…”

Pancreatic Neuroendocrine Tumors: an Update

“…The initial experiences with temozolamide and capacetabine, in the setting of metastatic pNETs disease, show a radiographic response rate of approximately 60 %, with an estimated median progression-free survival of 14 months, and median overall survival of 83 months [87][88][89]. Another advantage of this synergistic regimen is its favorable toxicity profile compared to streptomycin [87].…”

Whither peptide receptor radionuclide therapy for neuroendocrine tumors: an Einsteinian view of the facts and myths

“…Nonspecific chemotherapeutic regimes including streptozotocin in combination with 5-fluorouracil (FU) or temozolomide in combination with capecitabine have yielded promising results in a "select" subgroup of pancreatic NETs [20,21]. For grade 3 neuroendocrine cancers, even fewer treatment options are available, and conventional archaic cytotoxic chemotherapy schemes are usually applied [5,22].…”