학술논문
Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma.
Document Type
Academic Journal
Author
Kesari S; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Wagle N; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Carrillo JA; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Sharma A; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Nguyen M; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Truong J; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Gill JM; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Nersesian R; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Nomura N; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Rahbarlayegh E; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Barkhoudarian G; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Sivakumar W; Pacific Neuroscience Institute, Santa Monica, California.; Kelly DF; Pacific Neuroscience Institute, Santa Monica, California.; Krauss H; Pacific Neuroscience Institute, Santa Monica, California.; Bustos MA; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Hoon DSB; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.; Anker L; Providence St. Joseph Hospital Orange, Orange, California.; Singh AS; UCLA Health, Santa Monica Cancer Care, Santa Monica, California.; Sankhala KK; Cedars-Sinai Medical Center, Samuel Oschin Cancer Center, Los Angeles, California.; Juarez TM; Pacific Neuroscience Institute, Santa Monica, California.; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.
Source
Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE
Subject
Language
English
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.
(©2023 American Association for Cancer Research.)
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.
(©2023 American Association for Cancer Research.)