While some drugs might be used off-label while waiting for approval, others are used experimentally. Some cases are presented below.
Chemosensitivity improvement with malaria medication
A first example is described in [1], where patients with recurrent glioblastoma have been treated with a combination autophagy inhibitor chloroquine, usually used in malaria treatment and prevention [2], and the cell growth inhibitor vemurafenib or standard chemotherapeutics.
Trials both in adults and children showed that chloroquine improves vemurafenib sensitivity, and this combination could prove to be useful not only for brain tumours, but for other types of cancers, as well, as long as these cancers present a specific mutation (BRAFV600E), both in adults and children.
From the three patient this paper reports on, one has died of an intracranial haemorrhage; however, the other two presented an initial response, but also showed resistance to vemurafenib, suggesting scientists that combination therapies need to be developed.
Ex vivo experiments with chloroquine and vemurafenib showed improved sensitivity of the culture, being a possible solution for the patients that become treatment-resistant. Therefore, in the presence of the BRAFV600E biomarker, treatment response could be improved with a drug previously aimed to help other diseases.
Another paper showing the efficacy of chloroquine combined with the conventional surgery, chemotherapy, and radiotherapy in the treatment of glioblastoma is [3], that shows that survival time with chloroquine to be 25 +/- 3.4 months, and that in control subjects 11.4 +/- 1.3 months.The number of patients in this study is 41 additionally treated with chloroquine, and 82 who were not. As the numbers show, the mean survival time was doubled.
Image source: [4]
Cure for acne, another help in brain cancers
Other possible 'helps' in improving the efficacy of chemotherapy came up when I came upon an article about Prof Ben Williams, who, upon finding out he suffered from an immense glioblastoma, he started doing everything he could to improve his chances of survival. Therefore, he looked up possible methods to improve his response to chemotherapy (which followed his tumour removal surgery).[5] Drugs he took include : tamoxifen (used for breast cancer) together with aspirin (since tamoxifen causes blood clots), Verapamil (originally aimed to treat high blood pressure; here intended to improve the chemotherapy drug's penetration of the blood-brain barrier). Then, between his first and second round of chemotherapy, he started taking accutane (used for acne treatment, and which he was buying from Mexico, since it was not sold in the US). He also added melatonin (hormone that regulates sleep) and an immune-boosting mushroom supplement (which he still continues taking). Later during the chemotherapy, he started also taking gamma linolenic acid (an essential fatty acid thought to be important in brain function) in the form of borage seed oil. After four cycles of chemotherapy, all the residual tumour has vanished. [6]
Prof Ben Williams' Book. Image source:[7]
Cases like this , and the fact that the development of new cancer medication takes 10 year, costs more than 1 billion, and has a success rate of 10% [5] has led to starting the ReDO project [8] (Repurposing Drugs in Oncology), an international collaboration that seeks to re-purpose existing drugs, with low or no toxicity, that could be used in cancer treatment. Currently, they have identified around 70 agents, whose efficiency is being researched.
Such research is also carried out in Germany: as a 'cocktail' of medicine is being tested in treatment of recurrent glioblastoma. This composition is made of: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, sertraline, ritonavir. They are trying to inhibit the growth-enhancing pathways used by glioblastomas. [9]
Bibliography:
1), , , , , , , , , and
3)Briceño E1, Calderon A, Sotelo J.,Institutional experience with chloroquine as an adjuvant to the therapy for glioblastoma multiforme ,accessed from https://www.ncbi.nlm.nih.gov/pubmed/17350410 on 10 July 2017
4)https://www.seenso.com/index.php?dbname=Rose&i=24940040
5) The professor who 'cured' his cancer with a cocktail of everyday pills and 20 years on remains disease-free, accessed from http://www.telegraph.co.uk/lifestyle/wellbeing/healthadvice/11424747/The-professor-who-cured-his-cancer-with-a-cocktail-of-everyday-pills-and-20-years-on-remains-disease-free.html on 11 July 2017
6)Exploring Strategies for IDH1 Mutated Gliomas, http://astrocytomaoptions.com/exploring-strategies-for-idh1-mutated-gliomas/
7)https://www.amazon.co.uk/Surviving-Terminal-Cancer-Treatments-Oncologist/dp/1477496513
9)Kast RE, Karpel-Massler G, Halatsch ME., CUSP9* treatment protocol for recurrent glioblastoma: aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, sertraline augmenting continuous low dose temozolomide., accessed from https://www.ncbi.nlm.nih.gov/pubmed/25211298 on 11 July 2017