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

Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
Cancer (Impact Factor: 4.9). 01/2011; 117(2):268-75. DOI: 10.1002/cncr.25425
Source: PubMed

ABSTRACT 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).
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.
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.
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.

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    ABSTRACT: Background:O(6)-Methylguanine-DNA methyltransferase (MGMT) loss of expression has been suggested to be predictive of response to temozolomide in neuroendocrine tumours (NETs), but so far, only limited data are available. We evaluated the prognostic and predictive value of MGMT status, assessed by two molecular methods and immunohistochemistry, in a large series of NETs of different origins.Methods:A total of 107 patients, including 53 treated by alkylants (temozolomide, dacarbazine or streptozotocin), were retrospectively studied. In each case, we used methyl-specific PCR (MS-PCR) and pyrosequencing for evaluation of promoter methylation and immunohistochemistry for evaluation of protein status.Results:MGMT promoter methylation was detected in 12 out of 99 (12%) interpretable cases by MS-PCR and in 24 out of 99 (24%) by pyrosequencing. O(6)-Methylguanine-DNA methyltransferase loss of expression was observed in 29 out of 89 (33%) interpretable cases. Status of MGMT was not correlated with overall survival (OS) from diagnosis. Progression-free survival and OS from first alkylant use (temozolomide, dacarbazine and streptozotocin) were higher in patients with MGMT protein loss (respectively, 20.2 vs 7.6 months, P<0.001 and 105 vs 34 months, P=0.006) or MGMT promoter methylation assessed by pyrosequencing (respectively, 26.4 vs 10.8 months, P=0.002 and 77 vs 43 months, P=0.026).Conclusions:Our results suggest that MGMT status is associated with response to alkylant-based chemotherapy in NETs.British Journal of Cancer advance online publication, 13 January 2015; doi:10.1038/bjc.2014.660
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