Activity and Safety of Standard and Prolonged Capecitabine/Temozolomide Administration in Patients with Advanced Neuroendocrine Neoplasms.


Journal

Neuroendocrinology
ISSN: 1423-0194
Titre abrégé: Neuroendocrinology
Pays: Switzerland
ID NLM: 0035665

Informations de publication

Date de publication:
2019
Historique:
received: 25 10 2018
accepted: 02 04 2019
pubmed: 6 6 2019
medline: 30 5 2020
entrez: 6 6 2019
Statut: ppublish

Résumé

Capecitabine and temozolomide combination (CAPTEM) is associated with high response rates in patients with advanced neuroendocrine neoplasms (NENs). We evaluated the real-world activity and safety of CAPTEM from 3 NEN centers. Clinicopathological characteristics and outcomes of patients treated with CAPTEM for bulky or progressive disease (PD) were retrospectively analyzed. -Results: Seventy-nine patients with gastroenteropancreatic (grades 1-2 [n = 38], grade 3 [n = 24]) and lung/thymic (n = 17) NENs were included. Median treatment duration was 12.1 months (range 0.6-55.6). Overall, partial responses (PRs) occurred in 23 (29.1%), stable (SD) in 24 (30.4%), and PD in 28 (35.4%) patients. Median progression-free survival (PFS) and overall survival (OS) were 10.1 (6-14.2) and 102.9 months (43.3-162.5), respectively. On univariate analysis, NENs naive to chemotherapy and low Ki67 were associated with favorable responses (partial response [PR] + SD; p = 0.011 and 0.045), PFS (p < 0.0001 and 0.002) and OS (p = 0.005 and 0.001). Primary site (pancreas and lung/thymus) was also a significant prognostic factor for PFS (p < 0.0001) and OS (p < 0.0001). On multivariate analysis, gastrointestinal and unknown primary NENs (hazard ratio [HR] 0.3, 95% CI 0.1-0.8, p = 0.009 and p = 0.018) and prior surgery (HR 2.4, 95% CI 11-4.9, p = 0.021) were independent prognostic factors for PFS. Ki-67 was a poor predictor for favorable response in receiver operating characteristic analysis (area under the curve 0.678). Safety analysis of CAPTEM indicated rare events of serious (grades 3-4) toxicities (n = 4) and low discontinuation rates (n = 8) even in patients with prolonged administration (>12 months). CAPTEM treatment can be an effective and safe treatment even after prolonged administration for patients with NENs of various sites and Ki67 labeling index, associated with significant favorable responses and PFS.

Sections du résumé

BACKGROUND
Capecitabine and temozolomide combination (CAPTEM) is associated with high response rates in patients with advanced neuroendocrine neoplasms (NENs). We evaluated the real-world activity and safety of CAPTEM from 3 NEN centers.
METHODS
Clinicopathological characteristics and outcomes of patients treated with CAPTEM for bulky or progressive disease (PD) were retrospectively analyzed. -Results: Seventy-nine patients with gastroenteropancreatic (grades 1-2 [n = 38], grade 3 [n = 24]) and lung/thymic (n = 17) NENs were included. Median treatment duration was 12.1 months (range 0.6-55.6). Overall, partial responses (PRs) occurred in 23 (29.1%), stable (SD) in 24 (30.4%), and PD in 28 (35.4%) patients. Median progression-free survival (PFS) and overall survival (OS) were 10.1 (6-14.2) and 102.9 months (43.3-162.5), respectively. On univariate analysis, NENs naive to chemotherapy and low Ki67 were associated with favorable responses (partial response [PR] + SD; p = 0.011 and 0.045), PFS (p < 0.0001 and 0.002) and OS (p = 0.005 and 0.001). Primary site (pancreas and lung/thymus) was also a significant prognostic factor for PFS (p < 0.0001) and OS (p < 0.0001). On multivariate analysis, gastrointestinal and unknown primary NENs (hazard ratio [HR] 0.3, 95% CI 0.1-0.8, p = 0.009 and p = 0.018) and prior surgery (HR 2.4, 95% CI 11-4.9, p = 0.021) were independent prognostic factors for PFS. Ki-67 was a poor predictor for favorable response in receiver operating characteristic analysis (area under the curve 0.678). Safety analysis of CAPTEM indicated rare events of serious (grades 3-4) toxicities (n = 4) and low discontinuation rates (n = 8) even in patients with prolonged administration (>12 months).
CONCLUSIONS
CAPTEM treatment can be an effective and safe treatment even after prolonged administration for patients with NENs of various sites and Ki67 labeling index, associated with significant favorable responses and PFS.

Identifiants

pubmed: 31167197
pii: 000500135
doi: 10.1159/000500135
doi:

Substances chimiques

Antimetabolites, Antineoplastic 0
Antineoplastic Agents, Alkylating 0
Capecitabine 6804DJ8Z9U
Temozolomide YF1K15M17Y

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

333-345

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

© 2019 S. Karger AG, Basel.

Auteurs

Eleftherios Chatzellis (E)

1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece, e.chatzellis@endo.gr.
251 HAF and VA Hospital, Athens, Greece, e.chatzellis@endo.gr.

Anna Angelousi (A)

1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Kosmas Daskalakis (K)

1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Marina Tsoli (M)

1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Krystallenia I Alexandraki (KI)

1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Ewa Wachuła (E)

Department of Clinical Oncology and Radiotherapy, Medical University of Silesia, Katowice, Poland.

Amichay Meirovitz (A)

Oncology Department and Radiation Therapy Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Ofra Maimon (O)

Oncology Department and Radiation Therapy Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Simona Grozinsky-Glasberg (S)

Neuroendocrine Tumour Unit, Endocrinology and Metabolism Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

David Gross (D)

Neuroendocrine Tumour Unit, Endocrinology and Metabolism Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Beata Kos-Kudła (B)

Department of Endocrinology and Neuroendocrine Neoplasms, Department of Endocrinology and Pathophysiology, Medical University of Silesia, Katowice, Poland.

Anna Koumarianou (A)

Fourth Department of Internal Medicine, Hematology-Oncology Unit, Attikon University General Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Gregory Kaltsas (G)

1st Department of Propaedeutic Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.

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