Therapeutic Principles in the Management of Metastasising Carcinoid Tumors: Drugs for Symptomatic Treatment

Gregor, Michael

doi:10.1159/000201203

Cited by 17 publications

(10 citation statements)

References 22 publications

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“…Therefore, a number of somatostatin analogs have been developed that are less metabolically labile in plasma. The resulting longer plasma half-life of the analogs prolongs the plasma exposure that has resulted in approval of octreotide acetate for the treatment of patients with metastatic carcinoids or acromegaly (20)(21)(22)(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer

Whalen

White

Quinn

et al. 2019

Molecular Cancer Therapeutics

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Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma with a 95% mortality rate with no improvement to treatment in decades, and new therapies are desperately needed. PEN-221 is a miniaturized peptide-drug conjugate ($2 kDa) designed to target SCLC via a Somatostatin Receptor 2 (SSTR2)-targeting ligand and to overcome the high proliferation rate characteristic of this disease by using the potent cytotoxic payload, DM1. SSTR2 is an ideal target for a drug conjugate, as it is overexpressed in SCLC with limited normal tissue expression. In vitro, PEN-221 treatment of SSTR2-positive cells resulted in PEN-221 internalization and receptor-dependent inhibition of cellular proliferation. In vivo, PEN-221 exhibited rapid accumulation in SSTR2-positive SCLC xenograft tumors with quick clearance from plasma. Tumor accumulation was sustained, resulting in durable pharmacodynamic changes throughout the tumor, as evidenced by increases in the mitotic marker of G 2-M arrest, phosphohistone H3, and increases in the apoptotic marker, cleaved caspase-3. PEN-221 treatment resulted in significant antitumor activity, including complete regressions in SSTR2positive SCLC xenograft mouse models. Treatment was effective using a variety of dosing schedules and at doses below the MTD, suggesting flexibility of dosing schedule and potential for a large therapeutic window in the clinic. The unique attributes of the miniaturized drug conjugate allowed for deep tumor penetration and limited plasma exposure that may enable long-term dosing, resulting in durable tumor control. Collectively, these data suggest potential for antitumor activity of PEN-221 in patients with SSTR2-positive SCLC.

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Section: Introductionmentioning

confidence: 99%

Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer

Whalen

White

Quinn

et al. 2019

Molecular Cancer Therapeutics

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“…Although several subtypes of SSTR are expressed in endocrine tumors of the pancreas and gastrointestinal system, SSTR-2 is the most prominent type in more than 80% of these tumors (3,4), allowing the demonstration of GEP NETs with SRS and utilization of somatostatin analogues for adjunctive treatment (6)(7)(8). The synthetic so-F Fi ig gu ur re e 1 1. .…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of somatostatin receptor-2 positivity in gastroenteropancreatic neuroendocrine tumors in reference to known prognostic factors

Yenıay

Gurcu²,

Ünalp³

et al. 2012

Turk J Gastroenterol

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“…3,4 However, octreotide appears to be the most efficacious treatment for carcinoid syndrome reducing symptoms in more than 70% of patients. 14,15 Serotonin antagonists were used in the past with limited success but may still have a role as a second line treatment if octreotide therapy fails. Other pharmacological interventions suppressed symptoms only occasionally, and often resulted in significant side effects.…”

Section: Discussionmentioning

confidence: 99%

“…Other pharmacological interventions suppressed symptoms only occasionally, and often resulted in significant side effects. 14,15 The octreotide dosing regimen chosen for perioperative management consisted of 50 µg and a 50 µg iv injection prior to incision, followed by a continuous iv infusion of 50 µg·hr -1 , and additional 50 µg boluses to treat episodes of hemodynamic instability. The outlined dosing regimen seems to be the best documented.…”

Section: Discussionmentioning

confidence: 99%

Orthotopic liver transplantation for carcinoid tumour metastatic to the liver: anesthetic management

Claure

Drover

Haddow

et al. 2000

Can J Anesth/J Can Anesth

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Purpose: To report the anesthetic management of a patient with carcinoid tumour metastatic to the liver who presented for orthotopic liver transplantation. Anesthetic implications of metastatic carcinoid tumour on liver transplantation and the use of octreotide are discussed.Clinical features: A 51-yr-old woman with intestinal carcinoid tumour metastatic to the liver presented for orthotopic liver transplantation, a recent treatment option for patients with extensive hepatic carcinoid metastases and disabling symptoms unresponsive to conventional therapy. Despite continuous administration of the somatostatin analogue octreotide via a hepatic artery infusate pump, the patient suffered from daily break through symptoms, which included flushing, palpitations, paroxysmal hypertension, and dyspnea. The patient presented to the operating room with sinus tachycardia and severe arterial hypertension. Octreotide and phentolamine were used to prevent further mediator release and to control the paroxysmal hypertension. Midazolam, fentanyl, thiopental, succinylcholine, vecuronium, and isoflurane were used to induce and maintain anesthesia safely. An intravenous octreotide infusion was initiated after induction and continued throughout the case. Infrequent and non-threatening peaks in arterial blood pressure were readily treated with small intravenous doses of vasoactive drugs and octreotide. No other manifestations of the carcinoid syndrome occurred. The patient had an uneventful recovery and was discharged on postoperative day #6. Conclusion:The patient safely underwent orthotopic liver transplantation for treatment of symptomatic carcinoid tumour metastatic to the liver. The anesthetic management followed recent recommendations favouring the use of octreotide to prevent patients from becoming symptomatic. Outlined dosing regimen for octreotide provided satisfactory hemodynamic stability.Objectif : Présenter le traitement anesthésique d'une patiente atteinte d'une tumeur carcinoïde, avec métastase au foie, admise pour une transplantation hépatique orthotopique. Les implications anesthésiques de la tumeur sur la transplantation du foie et l'usage d'octréotide sont étudiées. Éléments cliniques : Une femme de 51 ans souffrant d'une tumeur intestinale carcinoïde, avec métastase au foie, s'est présentée pour une transplantation du foie orthotopique, une nouvelle option thérapeutique pour les patients chez qui les métastases carcinoïdes du foie sont étendues et les symptômes invalidants ne sont pas éliminés par la thérapie traditionnelle. Malgré l'administration continue d'un analogue de la somatostatine, l'octréotide, au moyen d'une perfusion insérée dans l'artère hépatique, la patiente souffrait d'une poussée quotidienne de symptômes qui comprenaient des bouffées vasomotrices, des palpitations, de l'hypertension paroxystique et de la dyspnée. À son arrivée à la salle d'opération, la patiente présentait une tachycardie sinusale et une hypertension artérielle sévère. Conclusion : La patiente a subi en toute sécurité une transpla...

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Therapeutic Principles in the Management of Metastasising Carcinoid Tumors: Drugs for Symptomatic Treatment

Cited by 17 publications

References 22 publications

Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer

Targeting the Somatostatin Receptor 2 with the Miniaturized Drug Conjugate, PEN-221: A Potent and Novel Therapeutic for the Treatment of Small Cell Lung Cancer

Prognostic value of somatostatin receptor-2 positivity in gastroenteropancreatic neuroendocrine tumors in reference to known prognostic factors

Orthotopic liver transplantation for carcinoid tumour metastatic to the liver: anesthetic management

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