First-in-Human Phase 1b Trial of Quinacrine Plus Capecitabine in Patients With Refractory Metastatic Colorectal Cancer.

Authors

• Arthur Winer
• Crystal S Denlinger
• Namrata Vijayvergia
• Steven J Cohen
• Igor Astaturov
• Efrat Dotan
• Jean-Nicolas Gallant
• Edward W Wang
• Miriam Kunkel
• Bora Lim
• Harold A Harvey
• Jeffrey Sivik
• Kenneth Korzekwa
• Karen Ruth
• Kevin White
• Harry S Cooper
• Eric A Ross
• Lanlan Zhou
• Wafik S El-Deiry

Publication/Presentation Date

3-1-2021

Abstract

BACKGROUND: Quinacrine plus a fluoropyrimidine has in vivo efficacy against metastatic colorectal cancer (mCRC). This phase 1b trial evaluated the combination of quinacrine plus capecitabine in patients with treatment-refractory mCRC.

PATIENTS AND METHODS: Using a modified Simon accelerated titration design, adults with treatment-refractory mCRC were treated with capecitabine 1000 mg/m

RESULTS: Ten patients (median age of 60 years) were treated in phase 1b. The first 2 quinacrine dosing levels were well tolerated. Dose-limiting toxicities were seen in 3 patients treated with quinacrine 200 mg twice daily. Five additional patients tolerated quinacrine 100 mg twice daily without further dose-limiting toxicities, thus establishing the maximum tolerated dose. Seven additional expansion-cohort patients enrolled onto the study before quinacrine manufacturing ceased within the United States. Five patients experienced stable disease, 1 partial response, and 10 disease progression. Median TTP overall was 2.12 months and median overall survival 5.22 months for the 17 patients.

CONCLUSION: Capecitabine and quinacrine can be safely administered at the maximum tolerated dose of capecitabine 1000 mg/m

Volume

20

Issue

1

First Page

43

Last Page

43

ISSN

1938-0674

Published In/Presented At

Winer, A., Denlinger, C. S., Vijayvergia, N., Cohen, S. J., Astaturov, I., Dotan, E., Gallant, J. N., Wang, E. W., Kunkel, M., Lim, B., Harvey, H. A., Sivik, J., Korzekwa, K., Ruth, K., White, K., Cooper, H. S., Ross, E. A., Zhou, L., & El-Deiry, W. S. (2021). First-in-Human Phase 1b Trial of Quinacrine Plus Capecitabine in Patients With Refractory Metastatic Colorectal Cancer. Clinical colorectal cancer, 20(1), e43–e52. https://doi.org/10.1016/j.clcc.2020.08.003

Disciplines

Medicine and Health Sciences

PubMedID

32972830

Department(s)

Hematology-Medical Oncology Division

Document Type

Article