ABSTRACT
Clear cell carcinoma is a rare and very aggressive subset of cervical cancer, with poor outcome if diagnosed at advanced stage. There are few data available on the optimal management of this histotype, and treatment recommendations that include surgery and chemoradiotherapy, are essentially based on those for squamous cell carcinoma. Here we report the case of a young patient newly diagnosed with advanced stage (FIGO IIB) clear cell carcinoma of the uterine cervix who received a window of opportunity one injection of nivolumab followed by standard chemoradiotherapy. She showed a persistent complete remission after 28 months of follow-up, but developed hypothyroidism, as a consequence of immunotherapy, and required lifelong thyroid hormone replacement.
ABSTRACT
PARP inhibitors (PARPi) have established themselves as a class of essential anti-cancer drugs. They inhibit PARP proteins involved in DNA damage repair. Their anti-tumor action requires a concomitant abnormality in DNA damage repair, the homologous recombination deficiency (HRD). The genomic instability being too substantial, the tumor cell goes into apoptosis (concept of synthetic lethality). This last decade, the selection of patients benefiting from PARPi has been refined with convincing results for ovarian cancers, but also breast, prostate and pancreatic cancers. This article presents recent data that have impacted our clinical practice and the PARPi authorized in Switzerland.
Les inhibiteurs de la PARP (poly-ADP-ribose-polymérase : iPARP) se sont imposés comme une classe de médicaments anticancéreux incontournable. Ils inhibent les protéines PARP impliquées dans la réparation de l'ADN. Leur action antitumorale nécessite une anomalie concomitante dans la réparation de l'ADN, le déficit de recombinaison homologue (HRD). L'instabilité génomique devenant trop conséquente, la cellule tumorale entre en apoptose (concept de synthetic lethality). La sélection des patient-e-s bénéficiant des iPARP s'est affinée cette dernière décennie avec des résultats probants pour les cancers de l'ovaire, mais aussi du sein, de la prostate et du pancréas. Cet article présente les données récentes ayant impacté notre pratique clinique et les iPARP autorisés en Suisse.
Subject(s)
Ovarian Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Male , Female , Humans , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Patient Selection , Ovarian Neoplasms/genetics , DNA Repair , Synthetic Lethal MutationsABSTRACT
Immunotherapy is becoming increasingly important in the management of urological, gynecological, and gastrointestinal cancers. Immune checkpoint inhibitor-based combinations have become a standard of care for patients with metastatic renal and liver cancers, as well as for many patients with bladder, cervical, gastric, and esophageal cancers, based on various biomarkers. Some tumor types are less responsive to immunotherapy, such as prostate and colon cancer. In these tumors, however, a subgroup of patients with a microsatellite-instability-high/DNA-mismatch repair deficient molecular phenotype significantly benefits from immunotherapy. Molecular characterization is therefore essential to identify patients who may benefit from these treatments. One of the major challenges is the search for new predictive biomarkers and novel combinations or strategies to further improve patient outcome.
Subject(s)
Gastrointestinal Neoplasms , Gynecology , Liver Neoplasms , Male , Humans , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/therapy , Immunotherapy , KidneyABSTRACT
High-dose intravenously (i.v) vitamin C in cancer patients is controversial. Numerous studies carried out on cancer cell lines and animal models demonstrated that millimolar vitamin C concentrations inhibit tumor cells viability, especially in association with chemotherapy. In cancer patients, high-dose i.v vitamin C in monotherapy does not show any anti-cancer activity. Clinical trials assessing high-dose i.v vitamin C concomitantly with chemotherapy do not conclude to reliable evidence for tumor control or overall survival benefit. Randomized double-blind trials are warranted.
La vitamine C administrée par voie intraveineuse (IV) chez les patients atteints de cancer est controversée. De nombreux travaux effectués sur des lignées cellulaires cancéreuses et des modèles animaux montrent que des concentrations plasmatiques pharmacologiques (≥ 15 mmol/l) de vitamine C sont capables de diminuer la viabilité des cellules cancéreuses. Chez les patients atteints de cancer, l'administration d'une haute dose IV de vitamine C seule ne montre pas de signe d'activité antitumorale. Elle a également été étudiée en association avec de la chimiothérapie, mais les essais cliniques réalisés ne permettent pas de conclure à un bénéfice pour les patients en termes de contrôle de la maladie oncologique ou de survie. Des études randomisées contre placebo et en double aveugle sont indispensables.
