May 16, 2020

A PHASE IIA STUDY REPOSITIONING DESIPRAMINE IN SMALL CELL LUNG CANCER AND OTHER HIGH-GRADE NEUROENDOCRINE TUMORS

Cancer Treatment and Research Communications
Jonathan W RiessJoel W Neal

Abstract

A bioinformatics approach identified antitumor effects of tricyclic antidepressants (TCAs) in small cell lung cancer (SCLC) and other high-grade neuroendocrine carcinomas (grade 3 neuroendocrine carcinomas) (G3NEC) that was subsequently validated in preclinical models with a putative mechanism of action via inhibition of neuroendocrine signaling pathways. This study was undertaken to reposition the candidate TCA desipramine in a clinical trial in SCLC and G3NEC. In this prospective, phase IIa intrapatient dose escalation clinical trial, patients were required to have failed at least one prior chemotherapy for metastatic SCLC or G3NEC. Treatment with desipramine began at 75 mg nightly with escalation in increments of 75 mg weekly to a maximum of 450 mg daily. Six patients were enrolled, 3 with SCLC, and 3 with G3NEC (lung, rectal, and pancreas). Tolerability of desipramine was worse than predicted. Of the 6 patients enrolled: 1 patient achieved 300 mg daily, 2 patients reached 150 mg daily, 1 patient reached 75 mg daily, and 2 patients were unable to tolerate any stable dose. Reasons for discontinuation included drug-related grade 3 colon pseudo-obstruction, unrelated GI bleed, and grade 1-2 neurocognitive adverse events. Median...Continue Reading

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Mentioned in this Paper

Ki-67 Antigen
Preclinical Study
Validation
Carcinoma, Neuroendocrine
Adverse Event
Pre-Clinical Model
Study
Small Cell Carcinoma of Lung
Pharmacologic Substance
Administration of Antineoplastic Agent

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