Peptide receptor radionuclide therapy with 177Lu-octreotate in patients with somatostatin receptor expressing neuroendocrine tumors six years' assessment

Mohammadali Hamiditabar, Muzammil Ali, Joseph Roys, Edward M. Wolin, Thomas M. O'Dorisio, David Ranganathan, Izabela Tworowska, Jonathan R. Strosberg, Ebrahim S. Delpassand

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Objectives: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a promising treatment for patients with inoperable, well to moderately differentiated metastatic neuroendocrine tumors (NETs). In continuation of our novel study with the radionuclide lutetium 177Lu, we now present further results of 177LuDOTATATE therapy inmanagingNETs and other somatostatin receptor-expressing tumors in a larger and more diverse patient group. Patients and Methods: One hundred forty-four consecutive patients (85men and 59 women; age range, 11-87 years;mean age, 58.5 years) with histologically confirmed NET were enrolled. One hundred forty-three patients received at least 1 cycle of treatment. Among them, 132 were deemed evaluable by having at least 1 cycle of treatment and a posttreatmentMRI or CT scan for assessment based on modified Response Evaluation Criteria in Solid Tumors. Response to therapy was evaluated in terms of progressionfree survival, overall survival, as well as radiologic, biochemical, and clinical responses. Further, analysis of symptoms was reviewed during therapy and also in subsequent follow-ups for safety evaluation. Renal, gastrointestinal (GI), hepatic, and hematological adverse events were evaluated using National Cancer Institute common toxicities criteria V4.03, through full blood panels, as well as consultation with patients for any symptoms and/or adverse events. Results: As of July 2016, median progression-free survival was about to be reached. Of 28 patients who have completed 177Lu DOTATATE therapy (completion of 4 or more cycles of treatment and all designated followups), no patient showed complete response (CR), 8 patients (28.57%) showed partial response (PR), 16 patients (57.14%) showed stable disease (SD), and progressive disease (PD) was observed in 4 patients (14.28%). The objective response rate (CR + PR) of this group was 28.57% (n = 8) with a cumulative disease control (CR + PR + SD) of 85.71% (n = 24). Among 132 evaluable patients, assessment of treatment response using modified Response Evaluation Criteria in Solid Tumors criteria revealed CR in none of the patients, PR in 12 patients (9.09%), SD in 66 patients (50%), whereas PD, which included patients who passed away, was observed in 54 patients (40.90%), yielding an objective response rate of 9.09% (n = 12) and a cumulative disease control rate of 59.09% (n = 78). Symptoms including abdominal pain, diarrhea, flushing, and fatigue improved in over 50% of the patients, whereas weight loss improved in 28.26% of the patients. No grade 3 or grade 4 renal toxicities were found, though eleven grade 3 and five grade 4 hematological as well as three grade 3 hepatotoxicities were reported. Grade 3 hematotoxicity lasted an average of 2.7 months, and grade 4 lasted for only 0.9 months, whereas grade 3 hepatotoxicity lasted an average of 3.1 months. Conclusions: 177Lu-octreotate peptide receptor radionuclide therapy has shown promising potential as a safe and effective targeted therapy in inoperable, well to moderately differentiated metastatic neuroendocrine cancers. The results of the multicenter randomized clinical trial conducted in United States and Europe are concordant with current study.

Original languageEnglish (US)
Pages (from-to)436-443
Number of pages8
JournalClinical Nuclear Medicine
Volume42
Issue number6
DOIs
StatePublished - 2017

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Somatostatin Receptors
Peptide Receptors
Neuroendocrine Tumors
Radioisotopes
Therapeutics
177Lu-octreotate
Lutetium
Kidney

Keywords

  • Lu-octreotate PRRT
  • Neuroendocrine tumors
  • Progression-free survival
  • Somatostatin receptor

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Peptide receptor radionuclide therapy with 177Lu-octreotate in patients with somatostatin receptor expressing neuroendocrine tumors six years' assessment. / Hamiditabar, Mohammadali; Ali, Muzammil; Roys, Joseph; Wolin, Edward M.; O'Dorisio, Thomas M.; Ranganathan, David; Tworowska, Izabela; Strosberg, Jonathan R.; Delpassand, Ebrahim S.

In: Clinical Nuclear Medicine, Vol. 42, No. 6, 2017, p. 436-443.

Research output: Contribution to journalArticle

Hamiditabar, M, Ali, M, Roys, J, Wolin, EM, O'Dorisio, TM, Ranganathan, D, Tworowska, I, Strosberg, JR & Delpassand, ES 2017, 'Peptide receptor radionuclide therapy with 177Lu-octreotate in patients with somatostatin receptor expressing neuroendocrine tumors six years' assessment', Clinical Nuclear Medicine, vol. 42, no. 6, pp. 436-443. https://doi.org/10.1097/RLU.0000000000001629
Hamiditabar, Mohammadali ; Ali, Muzammil ; Roys, Joseph ; Wolin, Edward M. ; O'Dorisio, Thomas M. ; Ranganathan, David ; Tworowska, Izabela ; Strosberg, Jonathan R. ; Delpassand, Ebrahim S. / Peptide receptor radionuclide therapy with 177Lu-octreotate in patients with somatostatin receptor expressing neuroendocrine tumors six years' assessment. In: Clinical Nuclear Medicine. 2017 ; Vol. 42, No. 6. pp. 436-443.
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abstract = "Objectives: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a promising treatment for patients with inoperable, well to moderately differentiated metastatic neuroendocrine tumors (NETs). In continuation of our novel study with the radionuclide lutetium 177Lu, we now present further results of 177LuDOTATATE therapy inmanagingNETs and other somatostatin receptor-expressing tumors in a larger and more diverse patient group. Patients and Methods: One hundred forty-four consecutive patients (85men and 59 women; age range, 11-87 years;mean age, 58.5 years) with histologically confirmed NET were enrolled. One hundred forty-three patients received at least 1 cycle of treatment. Among them, 132 were deemed evaluable by having at least 1 cycle of treatment and a posttreatmentMRI or CT scan for assessment based on modified Response Evaluation Criteria in Solid Tumors. Response to therapy was evaluated in terms of progressionfree survival, overall survival, as well as radiologic, biochemical, and clinical responses. Further, analysis of symptoms was reviewed during therapy and also in subsequent follow-ups for safety evaluation. Renal, gastrointestinal (GI), hepatic, and hematological adverse events were evaluated using National Cancer Institute common toxicities criteria V4.03, through full blood panels, as well as consultation with patients for any symptoms and/or adverse events. Results: As of July 2016, median progression-free survival was about to be reached. Of 28 patients who have completed 177Lu DOTATATE therapy (completion of 4 or more cycles of treatment and all designated followups), no patient showed complete response (CR), 8 patients (28.57{\%}) showed partial response (PR), 16 patients (57.14{\%}) showed stable disease (SD), and progressive disease (PD) was observed in 4 patients (14.28{\%}). The objective response rate (CR + PR) of this group was 28.57{\%} (n = 8) with a cumulative disease control (CR + PR + SD) of 85.71{\%} (n = 24). Among 132 evaluable patients, assessment of treatment response using modified Response Evaluation Criteria in Solid Tumors criteria revealed CR in none of the patients, PR in 12 patients (9.09{\%}), SD in 66 patients (50{\%}), whereas PD, which included patients who passed away, was observed in 54 patients (40.90{\%}), yielding an objective response rate of 9.09{\%} (n = 12) and a cumulative disease control rate of 59.09{\%} (n = 78). Symptoms including abdominal pain, diarrhea, flushing, and fatigue improved in over 50{\%} of the patients, whereas weight loss improved in 28.26{\%} of the patients. No grade 3 or grade 4 renal toxicities were found, though eleven grade 3 and five grade 4 hematological as well as three grade 3 hepatotoxicities were reported. Grade 3 hematotoxicity lasted an average of 2.7 months, and grade 4 lasted for only 0.9 months, whereas grade 3 hepatotoxicity lasted an average of 3.1 months. Conclusions: 177Lu-octreotate peptide receptor radionuclide therapy has shown promising potential as a safe and effective targeted therapy in inoperable, well to moderately differentiated metastatic neuroendocrine cancers. The results of the multicenter randomized clinical trial conducted in United States and Europe are concordant with current study.",
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TY - JOUR

T1 - Peptide receptor radionuclide therapy with 177Lu-octreotate in patients with somatostatin receptor expressing neuroendocrine tumors six years' assessment

AU - Hamiditabar, Mohammadali

AU - Ali, Muzammil

AU - Roys, Joseph

AU - Wolin, Edward M.

AU - O'Dorisio, Thomas M.

AU - Ranganathan, David

AU - Tworowska, Izabela

AU - Strosberg, Jonathan R.

AU - Delpassand, Ebrahim S.

PY - 2017

Y1 - 2017

N2 - Objectives: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a promising treatment for patients with inoperable, well to moderately differentiated metastatic neuroendocrine tumors (NETs). In continuation of our novel study with the radionuclide lutetium 177Lu, we now present further results of 177LuDOTATATE therapy inmanagingNETs and other somatostatin receptor-expressing tumors in a larger and more diverse patient group. Patients and Methods: One hundred forty-four consecutive patients (85men and 59 women; age range, 11-87 years;mean age, 58.5 years) with histologically confirmed NET were enrolled. One hundred forty-three patients received at least 1 cycle of treatment. Among them, 132 were deemed evaluable by having at least 1 cycle of treatment and a posttreatmentMRI or CT scan for assessment based on modified Response Evaluation Criteria in Solid Tumors. Response to therapy was evaluated in terms of progressionfree survival, overall survival, as well as radiologic, biochemical, and clinical responses. Further, analysis of symptoms was reviewed during therapy and also in subsequent follow-ups for safety evaluation. Renal, gastrointestinal (GI), hepatic, and hematological adverse events were evaluated using National Cancer Institute common toxicities criteria V4.03, through full blood panels, as well as consultation with patients for any symptoms and/or adverse events. Results: As of July 2016, median progression-free survival was about to be reached. Of 28 patients who have completed 177Lu DOTATATE therapy (completion of 4 or more cycles of treatment and all designated followups), no patient showed complete response (CR), 8 patients (28.57%) showed partial response (PR), 16 patients (57.14%) showed stable disease (SD), and progressive disease (PD) was observed in 4 patients (14.28%). The objective response rate (CR + PR) of this group was 28.57% (n = 8) with a cumulative disease control (CR + PR + SD) of 85.71% (n = 24). Among 132 evaluable patients, assessment of treatment response using modified Response Evaluation Criteria in Solid Tumors criteria revealed CR in none of the patients, PR in 12 patients (9.09%), SD in 66 patients (50%), whereas PD, which included patients who passed away, was observed in 54 patients (40.90%), yielding an objective response rate of 9.09% (n = 12) and a cumulative disease control rate of 59.09% (n = 78). Symptoms including abdominal pain, diarrhea, flushing, and fatigue improved in over 50% of the patients, whereas weight loss improved in 28.26% of the patients. No grade 3 or grade 4 renal toxicities were found, though eleven grade 3 and five grade 4 hematological as well as three grade 3 hepatotoxicities were reported. Grade 3 hematotoxicity lasted an average of 2.7 months, and grade 4 lasted for only 0.9 months, whereas grade 3 hepatotoxicity lasted an average of 3.1 months. Conclusions: 177Lu-octreotate peptide receptor radionuclide therapy has shown promising potential as a safe and effective targeted therapy in inoperable, well to moderately differentiated metastatic neuroendocrine cancers. The results of the multicenter randomized clinical trial conducted in United States and Europe are concordant with current study.

AB - Objectives: Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a promising treatment for patients with inoperable, well to moderately differentiated metastatic neuroendocrine tumors (NETs). In continuation of our novel study with the radionuclide lutetium 177Lu, we now present further results of 177LuDOTATATE therapy inmanagingNETs and other somatostatin receptor-expressing tumors in a larger and more diverse patient group. Patients and Methods: One hundred forty-four consecutive patients (85men and 59 women; age range, 11-87 years;mean age, 58.5 years) with histologically confirmed NET were enrolled. One hundred forty-three patients received at least 1 cycle of treatment. Among them, 132 were deemed evaluable by having at least 1 cycle of treatment and a posttreatmentMRI or CT scan for assessment based on modified Response Evaluation Criteria in Solid Tumors. Response to therapy was evaluated in terms of progressionfree survival, overall survival, as well as radiologic, biochemical, and clinical responses. Further, analysis of symptoms was reviewed during therapy and also in subsequent follow-ups for safety evaluation. Renal, gastrointestinal (GI), hepatic, and hematological adverse events were evaluated using National Cancer Institute common toxicities criteria V4.03, through full blood panels, as well as consultation with patients for any symptoms and/or adverse events. Results: As of July 2016, median progression-free survival was about to be reached. Of 28 patients who have completed 177Lu DOTATATE therapy (completion of 4 or more cycles of treatment and all designated followups), no patient showed complete response (CR), 8 patients (28.57%) showed partial response (PR), 16 patients (57.14%) showed stable disease (SD), and progressive disease (PD) was observed in 4 patients (14.28%). The objective response rate (CR + PR) of this group was 28.57% (n = 8) with a cumulative disease control (CR + PR + SD) of 85.71% (n = 24). Among 132 evaluable patients, assessment of treatment response using modified Response Evaluation Criteria in Solid Tumors criteria revealed CR in none of the patients, PR in 12 patients (9.09%), SD in 66 patients (50%), whereas PD, which included patients who passed away, was observed in 54 patients (40.90%), yielding an objective response rate of 9.09% (n = 12) and a cumulative disease control rate of 59.09% (n = 78). Symptoms including abdominal pain, diarrhea, flushing, and fatigue improved in over 50% of the patients, whereas weight loss improved in 28.26% of the patients. No grade 3 or grade 4 renal toxicities were found, though eleven grade 3 and five grade 4 hematological as well as three grade 3 hepatotoxicities were reported. Grade 3 hematotoxicity lasted an average of 2.7 months, and grade 4 lasted for only 0.9 months, whereas grade 3 hepatotoxicity lasted an average of 3.1 months. Conclusions: 177Lu-octreotate peptide receptor radionuclide therapy has shown promising potential as a safe and effective targeted therapy in inoperable, well to moderately differentiated metastatic neuroendocrine cancers. The results of the multicenter randomized clinical trial conducted in United States and Europe are concordant with current study.

KW - Lu-octreotate PRRT

KW - Neuroendocrine tumors

KW - Progression-free survival

KW - Somatostatin receptor

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