Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma.

Publication Title

Clinical cancer research : an official journal of the American Association for Cancer Research

Authors

Santosh Kesari, Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute/Pacific Neuroscience Institute, 2200 Santa Monica Boulevard, Santa Monica, CA, 90404, USAFollow
Naveed Wagle, Pacific Neuroscience Institute, Santa Monica, California, USA; Department of Translational Neurosciences, Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USAFollow
Jose Carrillo, Pacific Neuroscience Institute, Santa Monica, California, USA; Department of Translational Neurosciences, Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California, USAFollow
Akanksha Sharma, Department of Translational Neurosciences, Pacific Neuroscience Institute at Saint John Cancer Institute, Santa Monica, CA, USAFollow
Minhdan Nguyen, Department of Translational Neurosciences and Neurotherapeutics, Pacific Neuroscience Institute, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USAFollow
Judy D Truong, Department of Translational Neurosciences and Neurotherapeutics, Pacific Neuroscience Institute, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA, USAFollow
Jaya Mini Gill, John Wayne Cancer InstituteFollow
Raffi Nersesian, ProvidenceFollow
Natsuko Nomura, John Wayne Cancer Institute and Pacific Neuroscience Institute at Providence Saint John's Health Center, Santa Monica, CA, USA.Follow
Elnaz Rahbarlayegh, Pacific Neuroscience Institute, Santa Monica, California.Follow
Garni Barkhoudarian, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, California, USA.Follow
Walavan Sivakumar, Department of Neurosurgery, Pacific Neuroscience Institute, Santa Monica, California, United States.Follow
Daniel F Kelly, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, California, USA.Follow
Howard Krauss, Pacific Neuroscience Institute, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CaliforniaFollow
Matias A Bustos, Department of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI) at Providence Saint John's Health Center, Santa MonicaFollow
Dave HoonFollow
Lars Anker, Center for Cancer Prevention and Treatment, St. Joseph Hospital, Orange, Calif.Follow
Arun S Singh
Kamalesh K Sankhala
Tiffany Juarez, Department of Translational Neurosciences and Neurotherapeutics, Pacific Neuroscience Institute, John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA.Follow

Document Type

Article

Publication Date

1-17-2024

Keywords

california; pni; sjci; pacific neurosci; covid-19; Adult; Humans; Pemetrexed; Chordoma; Pilot Projects; Glutamates; Guanine; Neoplasm Staging; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Lung Neoplasms

Abstract

PURPOSE: Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma.

PATIENTS AND METHODS: Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers.

RESULTS: Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4-31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months-undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms.

CONCLUSIONS: High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.

Area of Special Interest

Neurosciences (Brain & Spine)

Area of Special Interest

Cancer

Area of Special Interest

Mental Health

Specialty/Research Institute

Infectious Diseases

Specialty/Research Institute

Behavioral Health

Specialty/Research Institute

Neurosciences

DOI

10.1158/1078-0432.CCR-23-2317