Is artesunate (an antimalarial medication) effective and safe for cancer treatment?

Artesunate for Cancer Treatment

Primary Recommendation

Artesunate should NOT be used for cancer treatment outside of clinical trials, as no major oncology guidelines support its use for this indication, and standard-of-care cancer therapies must not be delayed or replaced. 1

Evidence-Based Rationale

Lack of Guideline Support

• The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) do not recommend artesunate for cancer treatment 1
• The European Society for Medical Oncology and other major oncology societies have not established guidelines for artesunate use in cancer, highlighting the critical gap in evidence 1
• No survival data or established optimal dosing exists for cancer treatment applications 1

Discordance Between Laboratory and Clinical Evidence

The evidence reveals a striking disconnect between preclinical promise and clinical reality:

Preclinical Activity:

• Artesunate demonstrated activity against 55 cancer cell lines with GI50 values comparable to established cytostatic drugs, showing particular efficacy against leukemia (1.11±0.56 μM) and colon cancer (2.13±0.74 μM) cell lines 2
• The drug induces oxidative DNA damage, sustained DNA double-strand breaks, and activates the ATM/ATR damage response pathway in cancer cells 3

Clinical Reality:

• A phase I trial in metastatic breast cancer patients found doses up to 200 mg/day (2.2-3.9 mg/kg/day) were tolerable but demonstrated only safety data, not efficacy 4
• Testing in patient-derived cancer spheroids (PDCS) showed that only 84.62% of 39 samples responded to artesunate, with a mean inhibitory effect of merely 13.87%—2-fold weaker than standard cytostatic monotherapies 5
• Critical concern: 15.38% of PDCS models showed tumor stimulation up to 16.30%, and combined testing with chemotherapy resulted in chemo-stimulation in eight samples (up to 36.90%) 5

Safety Considerations for Cancer Use

If artesunate were to be considered off-label in refractory cases, extensive monitoring would be required:

• Post-artesunate delayed hemolysis (PADH) occurs in approximately 37.4% of patients treated for severe malaria 6, 1
• Mandatory monitoring would include: complete blood count with reticulocytes, NTproBNP, hemoglobin/haptoglobin/LDH at days 7,14,21, and 28, plus audiometry and neurological examination 1, 4
• Dose-limiting adverse events in the phase I trial included leucopenia, neutropenia, asthenia, and anemia 4

Clinical Algorithm

For patients inquiring about artesunate for cancer:

1. Explain that artesunate is FDA-approved only for malaria treatment 6, 7
2. Direct patients to clinical trials if they wish to access artesunate for cancer 1
3. Emphasize that standard-of-care cancer therapies must not be delayed 1
4. If patient has refractory disease with no standard options remaining, enrollment in a formal clinical trial is the only appropriate pathway 1

Critical Pitfalls to Avoid

• Do not prescribe artesunate off-label for cancer based on in vitro data alone—the complexity of tumor models dramatically affects efficacy, with patient-derived models showing minimal benefit 5
• Beware of potential tumor stimulation—artesunate can paradoxically enhance tumor growth in some cases and may stimulate rather than inhibit chemotherapy effects 5
• Do not assume the excellent safety profile in short-term malaria treatment translates to long-term cancer therapy—chronic use requires different safety considerations 4