One of the diseases that most affects people worldwide, cancer has about 12 million new cases per year and causes more than eight million deaths, according to the National Cancer Institute José Alencar Gomes da Silva (Inca). Still according to data from Inca, between 2016 and 2017 about 600,000 Brazilians should be diagnosed with one of the over 100 different types of cancer, with approximately 180,000 cases of non-melanoma skin cancer, the most common in the country.

 

Currently, people diagnosed with cancer undergo a series of treatments that seek to destroy the diseased cells that form the cancerous tumor. Treatments may include surgery, radiation therapy, chemotherapy or bone marrow transplant according to each patient’s case.

Chemotherapy, one of the most common therapies against cancer, makes use of two types of medicaments for the treatment: drugs that act on specific molecular mechanisms, the so called targeted therapies; and the cytotoxic,  predominant form of treatment using toxic drugs which, besides eliminating tumor cells, cause a variety of adverse effects in patients.

 

According to Professor Rafael Linden, coordinator of the Master's Degree in Toxicology and Toxicological Analysis at Feevale University, doses of cytotoxic chemotherapy drugs used by patients are not individualized, so that, in general, all patients receive the same dose of medicine. The cytotoxic doses as docetaxel and 5-fluorouracil are adjusted based solely on the height and weight of the patient, while tamoxifen, commonly used in the treatment of breast cancer, does not go through any adjustment being prescribed to all patients a daily dose of 20mg.

 

According to Marina Venzon Antunes, professor of the Master's Degree in Toxicology and Toxicological Analysis, the lack of a fine adjustment of doses can cause increased toxicity in some people or even therapeutic failure in others. This is because not all people metabolize drugs in the same way. Genetic variations or external factors such as drug interactions may impair or enhance the activity of enzymes responsible for the biotransformation of drugs, which leads to accumulation or reduction of their concentration in the body.

 

Through the Master's degree in Toxicology and Toxicological Analysis, Feevale does a lot of researches that seek to personalize chemotherapy for people being treated. Currently, the following researches are developed: Genotypic and phenotypic evaluation of 5-fluorouracil metabolism and its relationship with the occurrence of toxicity in the treatment of cancer, led by Professor Linden, and Genotypic evaluation of the pharmacokinetics of docetaxel and its relationship with the occurrence of toxicity in the treatment cancer, led by professor Marina. In 2014 the research Genotype and phenotype CYP2D6 evaluation on tamoxifen metabolism in patients with breast cancer was finished, also carried out by Linden, and that follows the same line of personalized chemotherapy treatment.

The researches try to understand the process of metabolizing 5-fluorouracil drugs, docetaxel and tamoxifen in the body of patients, identifying the factors that are important for biotransformation and taking into account the different profiles of people in treatment. In this regard, the researchers accompany patients in the Oncology Center of the Hospital de Clínicas de Porto Alegre, Feevale’s partner in carrying out the research.

Patients undergo a series of tests, including the dosages of drugs, genetic and biochemical testing, and evaluation of demographic characteristics such as weight, height, gender and age. Based on examination results, responses to treatment and the concentration of drugs presented in the blood and saliva of the patients, the researchers establish relationships between these factors, creating parameters for the treatment individualization.

According to Marina, the research is not being done effectively, the adjustment of drug doses in patients followed by the researchers. However, the information obtained from these studies will, in the future, provide new research in which it is possible to have groups of patients using conventional treatment and patient groups receiving individualized doses, thus allowing comparison of the effectiveness of treatments.

 

"Once we know the factors that are important for metabolism and what are the genetic and environmental information to be evaluated, we can identify patients at risk of toxicity, who are possibly in need of a dose adjustment or some important drug interaction, and this can be reported to the doctor. "

Marina Venzon Antunes, professor of the Master's Degree in Toxicology and Toxicological Analysis.

 

“Through this approach we can greatly increase the number of people who will have therapeutic response and dramatically reduce those who have toxic events. Toxicity can be very severe, the patient can go to the ICU receive very expensive drugs to treat this toxicity. This then improves the effectiveness of the treatment and improves the safety and quality of life of patients. "

Rafael Linden, coordinator of the Master's Degree in Toxicology and Toxicological Analysis

Chemotherapy is a treatment that uses drugs to destroy sick cells forming a tumor. Within the human body, each drug acts in a different way. The medicaments are mixed with the blood and are carried to all parts of the body, destroying the diseased cells that are forming a tumor and blocking, also, the spread throughout the body. The patient may receive chemotherapy as the only treatment or combined with others, such as radiotherapy and/or surgery. Chemotherapy may be taken orally, intravenously, intramuscularly, subcutaneously, intracranially or topically. The duration of treatment is planned according to the type of tumor and will vary in each case.

*Source: Instituto Nacional de Câncer José Alencar Gomes da Silva