Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters











Database
Language
Publication year range
2.
Clin Colorectal Cancer ; 20(1): e43-e52, 2021 03.
Article in English | MEDLINE | ID: mdl-32972830

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/m2 twice daily for 14/21-day cycle, and escalating doses of quinacrine 100 mg daily, 100 mg twice daily, and 200 mg twice daily for 21 days. The primary endpoint was identifying the maximum tolerated dose, determining tolerability and safety. In an expansion cohort, it was overall response rate and time to tumor progression (TTP). 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/m2 by mouth twice daily on days 1-14 and quinacrine 100 mg by mouth twice daily on days 1-21 of a 21-day cycle in mCRC patients. Although the expansion study was halted early, TTP was in line with other studies of refractory mCRC, suggesting activity of this regimen in heavily pretreated patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Capecitabine/administration & dosage , Colorectal Neoplasms/drug therapy , Quinacrine/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine/adverse effects , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Drug Administration Schedule , Drug Resistance, Neoplasm , Humans , Male , Maximum Tolerated Dose , Middle Aged , Progression-Free Survival , Quinacrine/adverse effects
SELECTION OF CITATIONS
SEARCH DETAIL