Citation

Frankel P, Ruel C, Uche A, Choy E, Okuno S, Somiah N, Chow WA. Journal of Oncology 2022; 2022.

Copyright

(Copyright © 2022)

DOI

10.1155/2022/3691025

PMID

unavailable

Abstract

Background. This single-arm, multicenter, phase 2 study evaluated the safety and antitumor activity of pazopanib in patients with unresectable, pulmonary metastatic osteosarcoma. Patients and Methods. Patients with pulmonary metastatic osteosarcoma unresponsive to chemotherapy were eligible. Patients who received prior tyrosine kinase inhibitor therapy were excluded. Pazopanib at 800 mg once daily was administered for 28-day cycles. Tumor responses were evaluated by local radiology assessment 1 month prior to and after initiation of treatment to calculate tumor doubling time and after every even numbered cycle. The primary endpoints were progression-free survival at 4 months, concomitant with a demonstrated 30% increase in tumor doubling time relative to the pretreatment growth rate.

RESULTS. 12 patients (7 female) were enrolled. The study was terminated prematurely due to withdrawal of financial support by the sponsor. 8 subjects were eligible for the primary analysis, whereas 4 patients were in a predefined exploratory "slow-growing"cohort. In the "fast-growing"cohort, 3 of the 8 patients (37.5%) eligible for first-stage analysis were deemed "success"by the preplanned criteria, adequate to proceed to second-stage accrual. In addition, 1 of the 4 patients in the "slow-growing"cohort experienced a partial remission. Grade 1-2 diarrhea was the most common adverse event, and grade 3 events were infrequent.

CONCLUSION. This study illustrates a novel method of demonstrating positive drug activity in osteosarcoma by increasing tumor doubling time, and this is further supported by a partial response in a patient with "slow-growing"disease. This trial is registered with NCT01759303. © 2022 Paul Frankel et al.

Language: en

Keywords

adult; human; female; male; aged; suicide attempt; pain; fatigue; anorexia; vomiting; clinical article; high performance liquid chromatography; tachycardia; neutropenia; thrombocytopenia; lung embolism; drug safety; follow up; drug efficacy; nausea; drug withdrawal; multicenter study; computer assisted tomography; hypertension; financial management; cohort analysis; side effect; anemia; Caucasian; alanine aminotransferase; aspartate aminotransferase; leukocyte count; hyponatremia; hypothyroidism; dyspnea; dizziness; drug dose reduction; Article; bilirubin; phase 2 clinical trial; progression free survival; antineoplastic activity; heart ejection fraction; tumor volume; lung metastasis; osteosarcoma; pleura effusion; alkaline phosphatase; pazopanib; pharmacokinetic parameters; body weight loss; hand foot syndrome; inoperable cancer; tumor doubling time