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