In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 3_suppl ( 2014-01-20), p. 281-281
Abstract:
281 Background: A combination of capecitabine (CAP) and temozolomide (TEM) has been successfully used as first-line treatment in low-grade pancreatic neuroendocrine neoplasms (PNEN). We reviewed activity and toxicity of the same regimen in patients with advanced NEN with different primary and grading. Methods: Clinical data of patients who had received oral CAP 1500 mg/m2/day over 14 days bid plus oral TEM 150-200 mg/m2/day on days 10-14 of each 28-day cycle, were retrospectively reviewed. The methylenguanilmetiltransferase (MGMT) methylation-status (MGMT-gene 〉 5% = responders) and TS-polymorphisms (2R/2R, 2R/3R = responders, 3R/3R = non-responders) in tumor-tissue/peripheral-blood were evaluated by pyrosequencing. Results: Since March 2012, 29 patients were selected. The primary tumor was: pancreas in 14 patients (48%), gastrointestinal (GI) in 5 (17%), unknown in 2 (7%), lung in 8 (28%). According to 2010 WHO classification, Ki67 was 〈 2% (G1) in 3%, 3-20% (G2) in 45% patients, 〉 20% (G3) in 21% with two "low G3" (Ki67 21-30%), and unknown in 3%. Among lung: 7% typical and 21% atypical (Travis’ classification). 72% patients (21/29) were progressive on different therapies: peptide-receptor-radiotherapy (38%), chemotherapy (38%), everolimus (14%). Partial-response (PR) occurred in 14% (4/29) of patients (95% CI: 4-32), stable-disease (SD) in 59% (17/29) (95% CI: 39-77) mainly PNET. The two "low G3" responded. Disease control rate (PR+SD): 72% (95% CI: 53-87). Median TTP: 9 months (95% CI: 5.6-N.E.). Thrombocytopenia was the most frequent grade 3 toxicity, always temporary. All 4 PR patients had genotype 2R/3R-2R/2R investigated for the 28 base-pair (bp) variable number of tandem repeats (VNTR) in the 5'UTR of the TS-gene, and MGMT-gene inactivation by epigenetic silencing. Conclusions: This analysis suggests that CAP-TEM chemotherapy could be active and well tolerated in pretreated patients with advanced NEN of different origins and grading. This warrants a prospective investigation in a more homogeneous population (G2 and “low-G3” GEP NEN or lung carcinoids), in order to validate the predictive value of MGMT methylation-status and TS-polymorphisms.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2014.32.3_suppl.281
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2014
detail.hit.zdb_id:
2005181-5
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