title: A Partial Response to Reintroduced Chemotherapy in a Resistant Small Cell Lung Cancer Patient After Priming with RRx-001.
abstract: As an exceedingly recalcitrant and highly aggressive tumor type without Food and Drug Administration-approved treatment or a known cure, the prognosis of recurrent extensive stage platinum-resistant/refractory small cell lung cancer (SCLC) is worse than other types of lung cancer, and many other tumor types, given a response rate of less than 10% and an overall survival of less than six months. It was broadly classified into three groups based on the initial response to cisplatin/etoposide therapy, platinum-refractory, platinum-resistant, and platinum-sensitive, extensive stage SCLC inevitably relapses, at which point the only standard options are to rechallenge with the first-line chemotherapeutic regimen in the case of sensitive disease or to start the topoisomerase I inhibitor, topotecan. Sensitive disease is defined by a response to the first-line therapy and a treatment-free interval of at least 90 days, while the definitions of refractory and resistant disease, respectively, are nonresponse to the first-line treatment or relapse within 90 days. As an important predictor of response to the second-line treatment, the clinical cutoff of three months (or two months in some cases) for resistant and sensitive disease, which along with performance status prognostically separates patients into high- and low-risk categories, dictates subsequent management. This case report presents a resistant SCLC patient enrolled on a Phase II clinical trial called QUADRUPLE THREAT (formerly TRIPLE THREAT; NCT02489903) who responded to reintroduced platinum doublets after sequential priming with the resistance-reversing epi-immunotherapeutic agent, RRx-001. In the QUADRUPLE THREAT clinical trial, both during priming with RRx-001 and during sequential treatment with platinum doublets, the patient maintained a good quality of life and performance status.
authors.affiliation: EpicentRx, Mountain View, CA, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Oronsky
authors.affiliation: EpicentRx, Mountain View, CA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Caroen
authors.affiliation: Walter Reed Military Medical Center, Bethesda, MD, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Zeman
authors.affiliation: Walter Reed Military Medical Center, Bethesda, MD, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Quinn
authors.affiliation: Walter Reed Military Medical Center, Bethesda, MD, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Brzezniak
authors.affiliation: EpicentRx, Mountain View, CA, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Scicinski
authors.affiliation: Department of Bioengineering, UCSD, La Jolla, CA, USA.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cabrales
authors.affiliation: Moores Cancer Center, UCSD, La Jolla, CA, USA.
authors.forename: Tony R
authors.initials: TR
authors.lastname: Reid
authors.affiliation: Center for Cancer Research National Cancer Institute, Bethesda, MD, USA.
authors.forename: Jane B
authors.initials: JB
authors.lastname: Trepel
authors.affiliation: Innovexe, Palo Alto, CA, USA.
authors.forename: Nacer D
authors.initials: ND
authors.lastname: Abrouk
authors.affiliation: Moores Cancer Center, UCSD, La Jolla, CA, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Larson
authors.affiliation: InterWest Partners, Menlo Park, CA, USA.
authors.forename: Arnold
authors.initials: A
authors.lastname: Oronsky
authors.affiliation: University of Helsinki, Helsinki, Finland.
authors.forename: Harry E
authors.initials: HE
authors.lastname: Lybeck
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Day
authors.affiliation: Walter Reed Military Medical Center, Bethesda, MD, USA.
authors.forename: Corey A
authors.initials: CA
authors.lastname: Carter
keywords: RRx-001; epigenetic; platinum doublets; resensitization; resistance reversal; resistant SCLC