Loading...
1 results
Search Results
Now showing 1 - 1 of 1
- Pharmacovigilance study of certain new classes of targeted antineoplastic therapiesPublication . Jesus, Mafalda Martins de; Morgado, Manuel Augusto Nunes Vicente Passos; Duarte, Ana Paula CoelhoCancer is considered one of the most devastating causes of death in the world. Innovative and targeted therapies have become urgent in the treatment of cancer. Examples of these therapies include the following therapeutic classes: poly(ADP-ribose) polymerase inhibitors (PARPi), cyclin-dependent kinase inhibitors (CDK4/6 inhibitors) and tyrosine kinase inhibitors (TKIs). These therapies are generally associated with better patient outcomes, with greater specificity and fewer side effects, particularly on healthy tissues. However, the literature reveals a significant list of adverse effects associated with these drugs, which can lead to changes in the chemotherapy regimens, discontinuation of therapy and, ultimately, death. Several domains are affected, including the hematological, gastrointestinal, metabolic, and cognitive domain, among others. In addition, many of these drugs are approved in an accelerated manner, with minimal clinical benefit and an unknown risk of adverse effects in the general population. Pharmacovigilance of anticancer therapies is fundamental. The detection and management of adverse drug reactions (ADR) can improve the safety of cancer patients and help healthcare professionals identify possible undocumented ADR during clinical trials. In this context, this thesis focuses essentially on the pharmacovigilance of targeted anticancer drugs namely: olaparib, niraparib and talazoparib, which belong to the PARPi class; palbociclib, ribociclib and abemaciclib, which belong to the CDK4/6 inhibitors class; and cabozantinib and lorlatinib, which belong to the TKIs class. Through a retrospective, descriptive and statistical analysis, pharmacovigilance data from the Portuguese Pharmacovigilance System and the EudraVigilance database was collected and analyzed. Variables such as sex, age group, reporter group, geographic origin, individual cases reported by system organ classes, outcome, seriousness, seriousness criteria, most reported preferred terms (PTs) (20 most reported PTs were considered), action taken, number of concomitant medicines per individual case safety report and clinical indications were considered. Hematological disorders were highly associated with PARPi and CDK4/6 inhibitors, particularly anemia, neutropenia, thrombocytopenia, and leukopenia. In addition, metabolic disorders were mainly associated with lorlatinib and hormonal disorders such as hypothyroidism were very common in patients taking cabozantinib. Pneumonitis was associated with olaparib, and some cases of peripheral neuropathy were associated with palbociclib. In general, most cases were reported as serious and were characterized as having an unknown outcome Fatal cases were associated with all three therapeutic classes studied, particularly with CDK4/6 inhibitors. New knowledge about ADR of targeted therapies may help to define timely management and prevention measures and contribute to better develop guidelines on warnings and precautions to be taken when using these drugs. Pharmacovigilance actions become imperative in improving the quality of life of cancer patients at such a critical time in their lives.