Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2).

Abstract

PURPOSE:

The antimalarial drug artesunate (ART) is a promising candidate for cancer treatment as it displays anticancer effects in various models. While in short-term treatment of malaria, an excellent safety profile has been found for ART, the potential long-term treatment of cancer patients demands a phase I dose-finding clinical trial determining the daily ART dose which would be well tolerated as add-on therapy.

METHODS:

Patients with metastatic breast cancer were to receive either 100 or 150 or 200 mg oral ART daily as add-on to their guideline-based oncological therapy for a study period of four weeks with frequent clinical and laboratory monitoring until 4-8 weeks thereafter. According to the statistical design, recruitment was scheduled in groups of three patients in order not to miss a more than 33% frequency of dose-limiting adverse events (DL-AE) prior to dose escalation.

RESULTS:

Twenty-three patients were recruited, and all planned dose levels were applied. During the actual trial period of 4 ± 1 weeks, three patients experienced six DL-AEs altogether (leucopenia, neutropenia, asthenia, anemia) possibly related to ART (not exceeding 33% in any dose level).

CONCLUSIONS:

Up to 200 mg/d (2.2-3.9 mg/kg/d) oral ART were safe and well tolerated; therefore, 200 mg/d are recommended for phase II/III trials. Safety monitoring should include reticulocytes, NTproBNP, as well as audiological and neurological exploration.

• Authors: Cornelia von Hagens, Ingeborg Walter-Sack, Maren Goeckenjan, Julia Osburg, Brigitte Storch-Hagenlocher, Serkan Sertel, Michael Elsässer, Bjoern Andrew Remppis, Lutz Edler, Judith Munzinger, Thomas Efferth, Andreas Schneeweiss, Thomas Strowitzki
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 164 Issue 2 Pg. 359-369 (Jul 2017) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 28439738 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Antineoplastic Agents, Hormonal
• Artemisinins
• Artesunate

Topics

• Adult
• Aged
• Antineoplastic Agents, Hormonal (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Artemisinins (administration & dosage, adverse effects)
• Artesunate
• Breast Neoplasms (drug therapy)
• Drug Administration Schedule
• Female
• Humans
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Metastasis
• Prospective Studies
• Treatment Outcome