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

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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish
Pages (from-to)e43-e52
JournalClinical Colorectal Cancer
Issue number1
StatePublished - Mar 2021


  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols/administration & dosage
  • Capecitabine/administration & dosage
  • Colorectal Neoplasms/drug therapy
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Progression-Free Survival
  • Quinacrine/administration & dosage


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