A Brief Report of a Phase II trial Evaluating Efficacy and Safety of Hypomethylating Agent Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer

Cynthia X. Wei; Hirva Mamdani; Ryan Gentzler; Maitri Kalra; Susan Perkins; Sandra Althouse; Shadia I. Jalal

doi:10.1016/j.cllc.2023.03.003

A Brief Report of a Phase II trial Evaluating Efficacy and Safety of Hypomethylating Agent Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer

Cynthia X. Wei, Hirva Mamdani, Ryan Gentzler, Maitri Kalra, Susan Perkins, Sandra Althouse, Shadia I. Jalal

Research output: Contribution to journal › Article › peer-review

Abstract

• Epigenetic modifications including DNA methylation have been implicated in platinum resistance in small cell lung cancer tumors and cell lines. This Phase II study investigated the combination of hypomethylating agent guadecitabine in combination with carboplatin in relapsed extensive stage small cell lung cancer. • The addition of guadecitabine to carboplatin did not lead to meaningful improvement in survival of patients with relapsed extensive stage SCLC and was associated with considerable toxicity. The lack of benefit may have been mediated in part by alternate epigenetic modifications of chemo resistance in SCLC such as histone modifications. • Additional characterization of molecular subtypes and transcriptional modifications of SCLC with new tools such as cell free DNA are needed to develop new therapeutic approaches to relapsed extensive SCLC.

Original language	English (US)
Pages (from-to)	347-352
Number of pages	6
Journal	Clinical lung cancer
Volume	24
Issue number	4
DOIs	https://doi.org/10.1016/j.cllc.2023.03.003
State	Published - Jun 2023
Externally published	Yes

Keywords

Epigenetic modification
Platinum resistance
Relapsed small cell lung cancer

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

Access to Document

10.1016/j.cllc.2023.03.003

Cite this

@article{8478983c7ee84bec89f172ffae5afe0b,

title = "A Brief Report of a Phase II trial Evaluating Efficacy and Safety of Hypomethylating Agent Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer",

abstract = "• Epigenetic modifications including DNA methylation have been implicated in platinum resistance in small cell lung cancer tumors and cell lines. This Phase II study investigated the combination of hypomethylating agent guadecitabine in combination with carboplatin in relapsed extensive stage small cell lung cancer. • The addition of guadecitabine to carboplatin did not lead to meaningful improvement in survival of patients with relapsed extensive stage SCLC and was associated with considerable toxicity. The lack of benefit may have been mediated in part by alternate epigenetic modifications of chemo resistance in SCLC such as histone modifications. • Additional characterization of molecular subtypes and transcriptional modifications of SCLC with new tools such as cell free DNA are needed to develop new therapeutic approaches to relapsed extensive SCLC.",

keywords = "Epigenetic modification, Platinum resistance, Relapsed small cell lung cancer",

author = "Wei, {Cynthia X.} and Hirva Mamdani and Ryan Gentzler and Maitri Kalra and Susan Perkins and Sandra Althouse and Jalal, {Shadia I.}",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = jun,

doi = "10.1016/j.cllc.2023.03.003",

language = "English (US)",

volume = "24",

pages = "347--352",

journal = "Clinical lung cancer",

issn = "1525-7304",

publisher = "Elsevier",

number = "4",

}

TY - JOUR

T1 - A Brief Report of a Phase II trial Evaluating Efficacy and Safety of Hypomethylating Agent Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer

AU - Wei, Cynthia X.

AU - Mamdani, Hirva

AU - Gentzler, Ryan

AU - Kalra, Maitri

AU - Perkins, Susan

AU - Althouse, Sandra

AU - Jalal, Shadia I.

PY - 2023/6

Y1 - 2023/6

N2 - • Epigenetic modifications including DNA methylation have been implicated in platinum resistance in small cell lung cancer tumors and cell lines. This Phase II study investigated the combination of hypomethylating agent guadecitabine in combination with carboplatin in relapsed extensive stage small cell lung cancer. • The addition of guadecitabine to carboplatin did not lead to meaningful improvement in survival of patients with relapsed extensive stage SCLC and was associated with considerable toxicity. The lack of benefit may have been mediated in part by alternate epigenetic modifications of chemo resistance in SCLC such as histone modifications. • Additional characterization of molecular subtypes and transcriptional modifications of SCLC with new tools such as cell free DNA are needed to develop new therapeutic approaches to relapsed extensive SCLC.

AB - • Epigenetic modifications including DNA methylation have been implicated in platinum resistance in small cell lung cancer tumors and cell lines. This Phase II study investigated the combination of hypomethylating agent guadecitabine in combination with carboplatin in relapsed extensive stage small cell lung cancer. • The addition of guadecitabine to carboplatin did not lead to meaningful improvement in survival of patients with relapsed extensive stage SCLC and was associated with considerable toxicity. The lack of benefit may have been mediated in part by alternate epigenetic modifications of chemo resistance in SCLC such as histone modifications. • Additional characterization of molecular subtypes and transcriptional modifications of SCLC with new tools such as cell free DNA are needed to develop new therapeutic approaches to relapsed extensive SCLC.

KW - Epigenetic modification

KW - Platinum resistance

KW - Relapsed small cell lung cancer

UR - http://www.scopus.com/inward/record.url?scp=85152731577&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85152731577&partnerID=8YFLogxK

U2 - 10.1016/j.cllc.2023.03.003

DO - 10.1016/j.cllc.2023.03.003

M3 - Article

C2 - 37032265

AN - SCOPUS:85152731577

SN - 1525-7304

VL - 24

SP - 347

EP - 352

JO - Clinical lung cancer

JF - Clinical lung cancer

IS - 4

ER -

A Brief Report of a Phase II trial Evaluating Efficacy and Safety of Hypomethylating Agent Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this