ABSTRACT
BACKGROUND: Hypersensitivity reactions (HSRs) to platinum are an important issue in the treatment of patients (pts) with ovarian cancer (OC). Germline BRCA mutations have been proposed as a risk factor. We aimed at evaluating the incidence and severity of HSRs to platinum in OC pts. with known BRCA status. PATIENTS AND METHODS: We retrospectively analyzed 432 pts. from 5 Italian Centers. In addition, we performed a systematic review and meta-analysis of published series. RESULTS: Four hundred nine pts. received at least one prior platinum-based treatment line: 314 were BRCA wild type (77%) and 95 were BRCA mutated (23%). There was no statistical difference in exposure to platinum. Incidence of any grade HSRs was higher among BRCA mutated pts. [9% vs 18%, p = 0.019] and the time-to-HSRs curves show that the risk increases with the duration of platinum exposure, in BRCA mutated pts. more than in BRCA wild type. A multivariable analysis showed that harboring a germline BRCA mutation was related to a higher incidence of HSRs (HR: 1.84, 95% CI 1.00-3.99, p = 0.05) while having received pegylated liposomal doxorubicin (PLD) was related to a lower incidence of HSRs (HR: 0.03 95% CI 0.004-0.22, p = 0.001). The systematic review confirmed the higher incidence of HSRs in BRCA mutated pts., though heterogeneity among series was significant. CONCLUSIONS: In OC pts. with BRCA mutations, there is a significantly higher incidence of HSRs to carboplatin, not justified by longer drug exposure. On the other hand, PLD exerted a protective role in our series.
Subject(s)
BRCA1 Protein/genetics , BRCA2 Protein/genetics , Drug Hypersensitivity/genetics , Organoplatinum Compounds/adverse effects , Female , Genes, BRCA1 , Genes, BRCA2 , Germ-Line Mutation , Humans , Multicenter Studies as Topic , Observational Studies as Topic , Organoplatinum Compounds/therapeutic use , Retrospective StudiesABSTRACT
The case of a 37-year-old male diagnosed 16 years previously with ulcerative colitis, admitted on account of hemolytic anaemia and thrombocytopaenia that responded to immunosuppressive therapy, is reported. Despite various peculiarities discussed, this may be the first reported case of Evans' syndrome associated with ulcerative colitis.
