Temozolomide as Second or Third Line Treatment of Patients with Neuroendocrine Carcinomas

Olsen, I; Sørensen, Jens Benn; Federspiel, Birgitte; Kjær, Andreas; Hansen, Carsten P.; Knigge, Ulrich; Langer, Seppo W.

doi:10.1100/2012/170496

Cited by 71 publications

(79 citation statements)

References 12 publications

(19 reference statements)

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“…Notably, the recently published lack of response with topotecan alone, which belongs to the same family of topoisomerase type 1 inhibitor like irinotecan, indicates that the combination of drugs may be of added value (Olsen et al 2014). In the second-line setting, Welin et al (2011) also proposed temozolomide plus or minus 5-FU and bevacizumab as an option in patients with Ki67 above 20%, but no review of the pathological differentiation of the tumors was performed and results from one recent study did not confirm antitumor activity of temozolomide in NEC (Olsen et al 2012). We suggest that patients with well-differentiated G3-NET could have been enrolled in Welin's study (Vé layoudom-Cé phise et al 2013).…”

Section: Discussionmentioning

confidence: 98%

Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma

Hadoux¹,

Malka²,

Planchard³

et al. 2015

Endocrine-Related Cancer

128

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There is no standard for second-line chemotherapy in poorly differentiated grade 3 neuroendocrine carcinoma (G3-NEC) patients. We analyzed the antitumor efficacy of 5-fluorouracil and oxaliplatin (FOLFOX) chemotherapy in this population. A single-center retrospective analysis of consecutive G3-NEC patients treated with FOLFOX chemotherapy after failure of a cisplatinum-based regimen between December 2003 and June 2012 was performed. Progression-free survival (PFS), overall survival (OS), response rate, and safety were assessed according to RECIST 1.1 and NCI.CTC v4 criteria. Twenty consecutive patients were included (seven males and 13 females; median age 55; range 23-87 years) with a performance status of 0-1 in 75% of them. Primary location was gastroenteropancreatic in 12, thoracic in four, other in two, and unknown in two patients. There were 12 (65%) large-cell and 7 (30%) small-cell G3-NEC tumors, and 1 (5%) unknown. All patients had distant metastases. Twelve (60%) patients received FOLFOX as second-line treatment and 8 (40%) as third-line treatment or later and the median number of administered cycles was 6 (range 3-14). The median follow-up was 19 months. Median PFS was 4.5 months. Among the 17 evaluable patients, five partial responses (29%), six stable diseases (35%), and six progressive diseases (35%) were observed. Median OS was 9.9 months. Main Grade 3-4 toxicities were neutropenia (35%), thrombopenia (20%), nausea/vomiting (10%), anemia (10%), and elevated liver transaminases (10%). Our results indicate that the FOLFOX regimen could be considered as a second-line option in poorly differentiated G3-NEC patients after cisplatinum-based first-line treatment but warrant further confirmation in future larger prospective studies. Key Words" neuroendocrine carcinoma

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Section: Discussionmentioning

confidence: 98%

Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma

Hadoux¹,

Malka²,

Planchard³

et al. 2015

Endocrine-Related Cancer

128

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“…Limited data and no guidelines are currently available for managing patients with NET G3. The observation that most experts feel these cases to be different from NEC is supported by their first choice to use (Welin et al 2011, Hentic et al 2012, Olsen et al 2012, Olsen et al 2014, Hadoux et al 2015. Published trials have included very heterogeneous populations, which make direct comparisons impossible.…”

Section: Discussionmentioning

confidence: 99%

Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms

Heetfeld

Chougnet

Olsen

et al. 2015

Endocrine-Related Cancer

342

353

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Data on gastroenteropancreatic neuroendocrine neoplasms (NEN) G3 (well-differentiated neuroendocrine tumors (NET G3) and neuroendocrine carcinoma (NEC)) are limited. We retrospectively study patients with NET G3 and NEC from eight European centers. Data examined included clinical and pathological characteristics at diagnosis, therapies and outcomes. Two hundred and four patients were analyzed (37 NET G3 and 167 NEC). Median age was 64 (21-89) years. Tumor origin included pancreas (32%) and colon-rectum (27%). The primary tumor was resected in 82 (40%) patients. Metastatic disease was evident at diagnosis in 88% (liver metastases: 67%). Median Ki-67 index was 70% (30% in NET G3 and 80% in NEC; P!0.001). Median overall survival (OS) for all patients was 23 (95% CI: 18-28) months and significantly higher in NET G3 (99 vs 17 months in NEC; HRZ8.3; P!0.001). Platinum-etoposide first line chemotherapy was administered in 113 (68%) NEC and 12 (32%) NET G3 patients. Disease control rate and progression free survival (PFS) were significantly higher in NEC compared to NET G3 (P!0.05), whereas OS was significantly longer in NET G3 (PZ0.003). Second-and third-line therapies (mainly FOLFIRI and FOLFOX) were given in 79 and 39 of NEC patients; median PFS and OS were 3.0 and 7.6 months respectively after second-line and 2.5 and 6.2 months after third-line chemotherapy. In conclusion, NET G3 and NEC are characterized by significant differences in Ki-67 index and outcomes. While platinum-based chemotherapy is effective in NEC, it seems to have limited value in NET G3.

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“…Evidence for salvage therapy in patients progressing on first-line platinum-based regimens is very limited (table 1) [1,13,40,41,42,43,44,45]. Overall, response rates are lower (18% in the NORDIC NEC study), although small series have documented response rates of 23-40% with oxaliplatin-based (XELOX, FOLFOX) or irinotecan-based (FOLFIRI, IP) regimens.…”

Section: Treatmentmentioning

confidence: 95%