Artemisinin, a chemical compound extracted from the plant Artemisia annua, commonly used in Chinese medicine for treating for malaria, is considered to have anti-cancer properties based on in vitro/in vivo and few clinical studies. However, more well-defined larger clinical trials are needed to determine the conditions and dosage under which Artemisinin or artesunate, a derivative of artemisinin, may be safe and effective in cancer patients. Additionally, the patients should also be monitored for potential side-effects in these trials, before prescribing artesunate/artemisinin for cancer treatment.
What is Artemisinin?
Artemisinin is a chemical compound extracted from Artemisia annua, an annual herb native to China, belonging to the Asteraceae family. Various combinations with Artemisinin extracted from this herb have been traditionally used in Chinese medicine to treat several illnesses.
Artesunate is the semisynthetic product/derivative of artemisinin.
The plant Artemisia annua is also known by several other names such as sweet wormwood, qinghaosu, qing hao, sweet sagewort, sweet Annie and annual wormwood.
What are the Purported Uses/Benefits of Artemisinin?
Artemisia annua/Artemisinin has been used in traditional Chinese medicine for illnesses like:
Some of the other purported uses/benefits of Artemisia annua/Artemisinin/Artesunate are listed below:
- Chagas’ disease
- African sleeping sickness
- Pain reduction in patients with osteoarthritis
- Potential to treat cancer – being studied as a cancer treatment
What are the Side-effects of Artemisinin?
One or more of the following side-effects were found in some people after using artemisinin:
- skin rash
- loss of appetite
- hearing loss
- liver problems
- ringing in the ears
Apart from these side-effects, Artemisia annua extracts/artemisinin can cause complications in patients with gastrointestinal disorders and should hence be avoided. One should also avoid artemisinin if taking anti-seizure medications.
Artemisia extracts/artemisinin may induce CYP2B6 and CYP3A4 enzymes and hence may interact with cancer drugs or other drugs metabolized by these enzymes, thereby affecting their concentration/dosage and bioavailability.
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Does Artemisinin have Anti-Cancer Properties?
Cancer cells require a large amount of iron to proliferate. Artemisinin can react with iron to form free radicals which can kill the cells. When compared to normal cells, cancer cells are more susceptible to the cytotoxic effect of artemisinin.
Artemisinin may hence cause the cancer cells to self-destruct as well as stop proliferating and spreading.
Due to this property of artemisinin, many researchers believe that artemisinin could be considered as an alternative to many of the aggressive cancer therapies. However, so far only a few clinical trials evaluated the potential of artemisinin in cancer treatment. Below are the findings of some of these clinical studies associated with artemisinin use in cancer.
Studies associated with Use of Artemisinin in Cancer
Impact of Artesunate in Patients with Non-Small Cell Lung Cancer (NSCLC)
In a study done by the researchers from the Dongguan Kuanghua Hospital in China, they compared the efficacy and toxicity of artesunate (derivative of artemisinin) combined with NP (a chemotherapy regimen of vinorelbine and cisplatin) and NP alone in the treatment of 120 cases of advanced non-small cell lung cancer (NSCLC). (Zhu-Yi Zhang et al, Zhong Xi Yi Jie He Xue Bao., 2008)
Compared to those who received only the NP chemo regimen, patients who received artesunate combined with NP chemo had a slight increase in the short-term survival rate from 34.5% to 45.1%, a slight decrease in mean survival time from 45 weeks to 44 weeks and a slight increase of 1-year survival rate from 32.7% to 45.1%.
The study also found that the disease control rate of patients who received both artemisinin and chemo regimen was 88.2% which is slightly higher than those who received the chemo alone – 72.7%. The study didn’t find any significant difference in toxicity (myelosuppression and digestion reaction) between the two groups.
Overall, this study found that Artesunate may be beneficial in the treatment of NSCLC, as the patients treated with a combination of artesunate and chemotherapy had a slower cancer progression than those who didn’t receive artesunate along with the chemotherapy.
Impact of Intravenous Artesunate in Patients with Advanced Solid Tumor Malignancies
Inova Health System in Virginia, Georgetown University Medical Center in Washington DC and Carolinas HealthCare System in North Carolina, United States, carried out a phase I study in 19 patients with advanced solid cancer to find out the maximum tolerated dosage and dose-limiting toxicities of intravenous artesunate (derivative of artemisinin). (John F Deeken et al, Cancer Chemother Pharmacol., 2018)
Based on the study done in these 19 cancer patients, it was found that the maximum tolerated dosage of intravenous artesunate/artemisinin was 18 mg/kg. The researchers also concluded that the treatment was well tolerated, however, only a modest clinical activity was seen in this pre-treated population.
Impact of Oral Artesunate Therapy in Patients with Colorectal Cancer
In a clinical study done by the researchers from the Institute of Infection and Immunity, University of London and East Surrey Hospital in the United Kingdom, Johannes Gutenberg-University and Universitätsklinikum Tübingen in Germany and Dafra Pharma in Belgium, the researchers evaluated the anti-cancer effect and tolerability of oral artesunate (derivative of artemisinin) in 20 colorectal cancer patients. (Sanjeev Krishna et al, EBioMedicine., 2014)
9 colorectal cancer patients were given oral artesunate and 11 patients were given placebo before surgery. The study found that 12% more patients from the group which received artesunate had apoptosis of > 7% of cells compared to the placebo group. The study also found that during a mean follow up of 42 months, 1 patient who received artesunate and 6 patients who received placebo developed recurrent colorectal cancer.
The researchers concluded that Artesunate may have apoptotic and anti-proliferative properties in colorectal cancer and may be well tolerated.
Impact of Artesunate in Metastatic Uveal Melanoma
Researchers from the University Hospital of Erlangen in Germany evaluated the impact of Artesunate (derivative of artemisinin) combined with standard chemotherapy in patients with metastatic uveal melanoma. The study highlighted that the therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone. (Thomas G Berger et al, Oncol Rep., 2005)
Additionally, they mentioned that artesunate when taken in combination with a second drug was found to be promising in the uveal melanoma patients. They found that:
- One of the patients who received artesunate experienced a temporary response when taken along with a drug called Fotemustine.
- The second patient showed a disease stabilization and reduction in splenic and lung metastasis after receiving artesunate along with the second drug Dacarbazine and was alive 47 months after first diagnosis of stage IV uveal melanoma which otherwise, usually has a survival of 2-5 months.
Impact of Oral Artenimol-R/Artemisinin Derivative in Advanced Cervical Cancer
Researchers from the Dafra Pharma Ltd in Belgium evaluated the clinical benefits and safety of oral administration of Artenimol-R (a derivative of artemisinin) in 10 patients with advanced cervix carcinoma for 28 days. The study found that all 10 patients had a remission and the symptoms such as pain and vaginal discharge went away in a mean period of 7 days. (Frans Herwig Jansen et al, Anticancer Res., 2011)
Ototoxicity in Metastatic or Locally Advanced Breast Cancer Patients Treated with Artesunate as Add-on Therapy
Ototoxicity could be a potential safety concern in breast cancer patients treated with long term daily doses of Artesunate (a derivative of Artemisinin) therapy. Hence, researchers from different Institutions in Heidelberg, Germany, conducted a prospective, phase I dose-escalation study called The ARTIC M33/2 study to evaluate the safety and tolerability of Artesunate in 23 patients with advanced breast cancer. (Miriam König et al, Cancer Chemother Pharmacol., 2016)
The study found that:
- 4 patients had adverse events related to hearing problems, possibly due to the intake of Artesunate, even though none of these were classified as severe adverse events as they did not require treatment interruption.
- 4 patients had vertigo during the test phase, one of which was classified as severe adverse events, but was reversible post discontinuation of Artesunate.
Impact of Oral Artesunate in Patients with Metastatic Breast Cancer
The same open phase I trial (ARTIC M33/2) done by the researchers from different Institutions in Heidelberg, Germany, evaluated the safety and tolerability of long-term treatment with Artesunate (a derivative of artemisinin) in patients with metastatic breast cancer who were undergoing their cancer treatments. The study mentioned that in 13 patients with metastatic breast cancer, up to 200 mg/day oral Artesunate add-on therapy (2.3-4.1 mg/kg BW/day) in up to 37 treatment months did not result in any major safety concerns. (Cornelia von Hagens et al, Phytomedicine., 2019)
A very low number of clinical trials, especially small clinical trials with low number of patients, were conducted that evaluated the role of artemisinin in the treatment of different types of cancers. Although, different studies conducted with artemisinin as an add-on therapy with other cancer treatments indicated that artemisinin may have the potential to inhibit cancer, more well-designed larger clinical trials are needed to confirm the findings in different cancer types as well as evaluate the safety, right dosage and toxicity, before recommending artesunate/artemisinin for the treatment of cancer. Patients also need to be monitored for side effects before prescribing artesunate/artemisinin for cancer therapy.
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