Octreotide LAR Dosage and Survival Among Elderly Patients With Distant‐Stage Neuroendocrine Tumors

392 Background: Octreotide long-acting repeatable (LAR) is approved for the management of symptoms due to carcinoid syndrome and may delay tumor progression among patients with neuroendocrine tumors (NETs). It is unknown whether dosage of octreotide LAR has an impact on survival. The current analysis evaluates the impact of initial octreotide LAR dosage on survival of elderly patients with NETs. Methods: Distant stage NET patients diagnosed between 1/1999 and 12/2009 who had received octreotide LAR treatment within 12 months of diagnosis were identified from the SEER-Medicare database. Those under age 65, enrolled in HMOs, or without continuous enrollment in Medicare Parts A and B were excluded. We compared the five-year survival of NET patients based on dose per 28 days averaged over the initial 3 months: Group A, <= 20 mg; B, 21 to 30 mg; C, > 30 mg. Kaplan-Meier estimations and Cox proportional hazard modeling were used to examine the association between octreotide LAR dose and survival. Results: Among 214 distant stage patients (mean and median age at 74 years old) with octreotide LAR treatment, 73 (34%) received <= 20 mg, 82 (38%) received 21 – 30 mg, while 59 (28%) received >30 mg. Median survival for patients who received low, medium and high dosage levels were 20.8 (95% CI: 13.2 – 31.5), 32.6 (95% CI: 20.5 – 51.1), and 36.3 (95% CI: 24.8 – N/A) months respectively. The log rank test had a p-value of 0.006. Multivariate analyses showed that higher octreotide LAR dosage levels were associated with significant survival improvement for distant stage patients. Compared to patients with the low dosage level, patients with medium dosage (HR=0.52, P=0.002) and patients with high dosage (HR=0.48, P=0.004) had better five-year survival. The difference in survival between Groups B and C was not statistically significant. Conclusions: This population-based study suggests potential survival benefits for octreotide LAR 30 mg dosage level among elderly distant stage NET patients.

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Comment on the Paper by Lemelin et al. Entitled “Elderly Patients with Metastatic Neuroendocrine Tumors Are Undertreated and Have Shorter Survival: The LyREMeNET Study”

Neuroendocrinology ◽

10.1159/000504550 ◽

2019 ◽

Vol 110 (7-8) ◽

pp. 721-722

Author(s):

Alberto Bongiovanni ◽

Chiara Liverani ◽

Federica Recine ◽

Laura Mercatali ◽

Stefano Severi ◽

...

Keyword(s):

Elderly Patients ◽

Neuroendocrine Tumors

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177Lu-DOTATATE Plus Radiosensitizing Capecitabine Versus Octreotide Long-Acting Release as First-Line Systemic Therapy in Advanced Grade 1 or 2 Gastroenteropancreatic Neuroendocrine Tumors: A Single-Institution Experience

JCO Global Oncology ◽

10.1200/go.21.00103 ◽

2021 ◽

pp. 1167-1175

Author(s):

Swayamjeet Satapathy ◽

Bhagwant R. Mittal ◽

Ashwani Sood ◽

Apurva Sood ◽

Rakesh Kapoor ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Systemic Therapy ◽

Objective Response ◽

Progression Free Survival ◽

First Line ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Free Survival ◽

Octreotide Lar ◽

Treatment Naïve ◽

Long Acting

PURPOSE To compare the efficacy and safety of 177Lu-DOTATATE plus radiosensitizing capecitabine and octreotide long-acting release (LAR) as first-line systemic therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS Data of consecutive patients of advanced inoperable or metastatic grade 1 or 2 GEP-NETs treated with first-line 177Lu-DOTATATE plus radiosensitizing capecitabine or octreotide LAR from September 2012 to December 2019 were collected and analyzed for response, toxicity, and survival outcomes. RESULTS Seventy-six patients (median age: 53 years; range 14-81 years) with treatment-naïve advanced grade 1 or 2 GEP-NETs were included. Thirty-six patients received a median cumulative dose of 27.3 GBq of 177Lu-DOTATATE intravenously at 8-12 weeks' intervals along with 1,250 mg/m2 oral capecitabine on days 0-14 of each cycle of 177Lu-DOTATATE, whereas 40 patients were administered 30 mg octreotide LAR intramuscularly every 4 weeks. Using response evaluation criteria in solid tumor 1.1, the objective response rate was 38% in the 177Lu-DOTATATE arm compared with 15% in the octreotide LAR arm ( P = .025), whereas the disease control rates were 88% and 67% in 177Lu-DOTATATE and octreotide LAR arms, respectively ( P = .035). The median durations of progression-free survival in the 177Lu-DOTATATE and octreotide LAR arms were 54 months and 16 months, respectively ( P = .017), whereas the median overall survival was not reached and not significantly different across both the arms. Of the treatment-related adverse events, no major difference was observed in the occurrence of grade 3 or 4 toxicities between the two treatment arms. CONCLUSION First-line systemic 177Lu-DOTATATE plus radiosensitizing capecitabine achieved better radiologic response and longer progression-free survival compared with octreotide LAR in patients with advanced grade 1 or 2 GEP-NETs. Future randomized controlled trials are, however, required to determine the best treatment sequence for the treatment-naïve patients with advanced GEP-NETs.

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Chromogranin A: From Laboratory to Clinical Aspects of Patients with Neuroendocrine Tumors

International Journal of Endocrinology ◽

10.1155/2018/8126087 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 15

Author(s):

Paola Di Giacinto ◽

Francesca Rota ◽

Laura Rizza ◽

Davide Campana ◽

Andrea Isidori ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Phase Ii ◽

Chromogranin A ◽

Carcinoid Syndrome ◽

Phase Ii Trial ◽

Randomized Study ◽

Clinical Aspects ◽

Clinical Activity ◽

Octreotide Lar ◽

Well Differentiated

Background. Neuroendocrine tumors (NETs) are characterized by having behavior and prognosis that depend upon tumor histology, primary site, staging, and proliferative index. The symptoms associated with carcinoid syndrome and vasoactive intestinal peptide tumors are treated with octreotide acetate. The PROMID trial assesses the effect of octreotide LAR on the tumor growth in patients with well-differentiated metastatic midgut NETs. The CLARINET trial evaluates the effects of lanreotide in patients with nonfunctional, well-, or moderately differentiated metastatic enteropancreatic NETs. Everolimus has been approved for the treatment of advanced pancreatic NETs (pNETs) based on positive PFS effects, obtained in the treated group. Sunitinib is approved for the treatment of patients with progressive gastrointestinal stromal tumor or intolerance to imatinib, because a randomized study demonstrated that it improves PFS and overall survival in patients with advanced well-differentiated pNETs. In a phase II trial, pasireotide shows efficacy and tolerability in the treatment of patients with advanced NETs, whose symptoms of carcinoid syndrome were resistant to octreotide LAR. An open-label, phase II trial assesses the clinical activity of long-acting repeatable pasireotide in treatment-naive patients with metastatic grade 1 or 2 NETs. Even if the growth of the neoplasm was significantly inhibited, it is still unclear whether its antiproliferative action is greater than that of octreotide and lanreotide. Because new therapeutic options are needed to counter the natural behavior of neuroendocrine tumors, it would also be useful to have a biochemical marker that can be addressed better in the management of these patients. Chromogranin A is currently the most useful biomarker to establish diagnosis and has some utility in predicting disease recurrence, outcome, and efficacy of therapy.

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