Chemotherapy is one of the key systemic oncologic therapy options against tumors along with many others. This complex, yet effective, system often leads to a lot of side effects. Besides severe side effects, chemotherapy is also potentially harmful to the environment. By introducing new therapeutic solutions, the healthcare system is gradually moving away from conventional chemotherapy. The European Society for Medical Oncology (ESMO) has identified bladder cancer as being the next in line for chemotherapy-free treatment.
Chemotherapy
Chemotherapy is a systemic treatment method for malignant diseases that involves the use of cytostatics, drugs that destroy rapidly dividing cells. It is used to treat almost all types of cancer, either alone or in combination with other therapies, like monotherapy or polychemotherapy, which involves the use of multiple drugs. Neoadjuvant chemotherapy is the initial step of treatment before surgery or radiotherapy to reduce the tumor’s size, which helps in later treatment. It is mostly used in breast cancer, esophagus cancer, non-small cell lung cancer, and bladder cancer in 2 to 4 cycles. Adjuvant chemotherapy is administered after surgery or radiotherapy in 4 to 8 cycles if the tumor has been removed. Adjuvant chemotherapy aims to eliminate the tumor microplants, potential residue in the form of circulating cells, that can’t be surgically removed or detected. This reduces the risk of disease comeback and metastasis. It is used in many tumor seeds, such as breast cancer, stomach cancer, colon cancer or lung cancer. Chemotherapy is used for the treatment of advanced or metastatic diseases as palliative care to relieve pain, but also for complete healing of testicular cancer, ovarian cancer, and Hodgkin’s lymphoma.
Chemotherapy administration
Chemotherapy is most commonly administered through intravenous injections or perorally via capsules and tablets. The duration of intravenous administration can vary from a few minutes to a few days, depending on the protocol. Other ways include
- intramuscular or subcutaneous injections
- intraperitoneal injections into the peritoneal or other cavities
- intraarterial administration into the artery that carries blood to the tumor
- topical administration by using creams on the affected area.
The majority of cytostatics do not cross the blood-brain barrier. For some central nervous system tumors, this means that the drug must be applied intrathecally, into the space surrounding the spinal cord or between the brain and its meninges. For patients with damaged peripheral veins, it is possible to install the port catheter with a minor operation. Central or peripheral permanent catheters are installed subcutaneously, mostly into the upper part of the chest that is connected to the majority of veins. The cytostatic, dose, and administration frequency are precisely chosen by the treatment protocol. The dose is determined based on the patient’s body surface area. One administration of chemotherapy is called a cycle, after which follows a 1 to 3-week rest period. The therapy can be received in the day hospital or with hospitalization, depending on the protocol.
Some tumor cells are resistant to chemotherapy or become resistant during it!
Side effects
Besides destroying malignant cells, cytostatics also destroy the surrounding healthy cells, which can restrict therapy. However, the majority of cells recover after therapy is finished. Cytostatics affect the rapidly dividing cells, such as epithelial, intestinal, and blood cells, in addition to cancerous cells. The side effects are usually temporary, with their appearance and intensity being highly individual. The most common side effects are related to blood cells (leukopenia, neutropenia, thrombocytopenia, anemia) or the gastrointestinal tract (nausea, vomiting, diarrhea, mucositis). The side effects can be general, such as nausea, vomiting, appetite loss, and fatigue or organ-specific, such as hair loss, alopecia, cardiotoxicity, nephrotoxicity, neurotoxicity, lung changes, low sperm count or absolute infertility. In case of severe side effects, the dose can be decreased, a cycle can be cancelled, and in rare cases, chemotherapy can be stopped. Today, by using combinations of drugs, we can minimize side effects. By combining drugs, it is possible to lower the dose of each drug, which decreases the risk of side effects.
Bladder cancer
Targeted therapy and immunotherapy are currently in focus and being compared to standard chemotherapy in the field of oncologic therapy. In some cases, they have completely replaced chemotherapy. During their latest meeting in Madrid, the European Society for Medical Oncology (ESMO) declared that transitional cell carcinoma (urothelial cancer) could be the next in line for chemotherapy-free treatment. Bladder cancer is a malignant disease with high mortality and morbidity. Patients with metastatic transitional cell carcinoma often have comorbidities, such as kidney damage. Cytostatics used to treat bladder cancer, cisplatin and carboplatin, are eliminated by the kidneys. This restricts their safe consumption in patients with kidney damage.
A combination of the antibody pembrolizumab and enfortumab–vedotin, a conjugate of vedotin and anti-nectin-4 antibody, attracted a lot of attention in metastatic urothelial cancer therapy. The U.S. Food and Drug Administration (FDA) granted accelerated approval for this combination to patients who don’t qualify for cisplatin chemotherapy at the beginning of last year. This accelerated approval was based on results from phases 1 and 2 of a study that showed an objective response rate of 65% to 73%. In October of last year, a study was presented involving 886 participants. The combination of enfortumab-vedotin and pembrolizumab (EV-P) showed significantly better progression-free survival rates, overall survival rates, and objective response rates than conventional chemotherapy! These results are an indication of a possible complete replacement of conventional chemotherapy as the first-line treatment of metastatic urothelial cancer with immunotherapy.
Is this the end of chemotherapy?
Aside from metastatic urothelial cancer, lung cancer and breast cancer are only a few of many malignant diseases for which the options of treatment are expanding beyond standard chemotherapy. Modern technologies and therapies are not only minimizing the harmful consequences but also improving the patient’s outcome. However, chemotherapy still has an important role in oncology, with minimal side effects when using the correct protocol. More and more studies compare immunotherapy and targeted therapy with chemotherapy and offer alternative ways of treatment for patients who are unable to safely undergo chemotherapy. The study presented during the latest ESMO meeting is very significant for the progress of oncologic therapy.
Translated by: Lara Mužević
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