Chemotherapy as a Tablet Instead of an Intravenous Infusion

Tuesday, March 28, 2017 Drug News
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Coming Wednesday (29 March 2017), Dutch pharmacist Emilia Sawicki will be defending her doctoral thesis in which she describes how some anticancer medicines can be formulated in such a way that patients take chemotherapy orally as a tablet, rather than as an intravenous infusion at the hospital. One of the anticancer medicines for which she developed a tablet formulation is the widely used drug docetaxel. The formulation is a tablet which is made as a ‘solid dispersion’, and was co-developed by Sawicki at the Slotervaart Medical Centre and the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital in Amsterdam. The discovery has already progressed to an advanced stage in the clinical development: shortly, a clinical trial will be opened at several Dutch hospitals where patients with prostate cancer will be treated with the solid dispersion tablet of docetaxel.

Anticancer medicines are increasingly being used as capsules or tablets. Oral medicines are more patient-friendly than the traditional way of administration the chemotherapy as an intravenous infusion. Patients can take the medicine at home as a tablet and no longer have to travel to a hospital to receive chemotherapy. One of the requirements is that the anticancer medicine dissolves in water in order to be effectively taken up in the blood. Dissolution is better if a ‘solid dispersion’ is used: a mixture of tiny particles of powdered medication, which dissolve faster and better in water than larger particles, such as crystalline powders.

In her doctoral thesis ‘Solid dispersions in oncology: a solution to solubility-limited oral drug absorption’, Sawicki describes a new production method for solid dispersions of docetaxel and paclitaxel, two anticancer medicines that are often prescribed to patients with prostate cancer, breast cancer and lung cancer. For example, docetaxel is prescribed approximately 24,000 times a year to cancer patients in the Netherlands. As a solid form docetaxel and paclitaxel are not well absorbed in the blood. This is because they are very poorly soluble in water and because they are broken down by enzymes in the gastrointestinal tract and liver. The solid dispersion method increases the dissolution of docetaxel and paclitaxel 40 to 100 times and when co-administered with enzyme inhibitor ritonavir these anticancer medicines are then effectively absorbed in the blood. As a result, many patients experience a highly promising anticancer effect.

Moreover, the production method for the solid dispersion tablet of docetaxel is suitable to supply the medicine on a large scale and this makes it possible to conduct large clinical trials. Amsterdam-based biopharmaceutical company Modra Pharmaceuticals is launching shortly several clinical trials with the solid dispersion tablet of docetaxel.

In addition, Sawicki also used the solid dispersion technique to develop a tablet formulation of elacridar, a medicine predominantly used in studies focusing on brain tumours, since elacridar promotes the absorption of other anticancer medicines in the brain

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