ABSTRACT
Tamoxifen may lead to bothersome side effects contributing to non-compliance and decreased quality of life. Patients searching for relief are increasingly turning to cannabinoids such as CBD-oil. However, CBD-oil might affect tamoxifen pharmacokinetics (PK) through CYP2D6 inhibition. The aims of this open-label, single-arm study were (1) to determine the PK profile of tamoxifen when using CBD-oil, and (2) to subsequently investigate whether CBD-oil has a beneficial influence on side effects. Study patients had to have steady-state endoxifen concentrations ≥16 nM (conservative threshold). PK sampling and side effect assessment was done at initiation of CBD-oil and 28 days thereafter. Bio-equivalence could be concluded if the 90% confidence interval (CI) for the difference in endoxifen AUC fell within the [-20%; +25%] interval. The effect of CBD-oil on side effects was evaluated using the FACT-ES questionnaire. Endoxifen AUC decreased after CBD-oil by 12.6% (n = 15, 90% CI -18.7%, -6.1%) but remained within bio-equivalence boundaries. The endocrine sub-scale of the FACT-ES improved clinically relevant with 6.7 points (n = 26, p < 0.001) and health-related quality of life improved with 4.7 points after using CBD (95% CI + 1.8, +7.6). We conclude that CBD-oil, if of good quality and with a dosage below 50 mg, does not have to be discouraged in patients using it for tamoxifen-related side effects. Clinical trial registration: International Clinical Trial Registry Platform (NL8786; https://www.who.int/clinical-trials-registry-platform ).
ABSTRACT
Since 2017, the non-invasive prenatal test (NIPT) has been offered to all pregnant woman in the Netherlands in the context of the TRIDENT-2 study, which has been implemented as a trial within the Dutch national screening programme for Down's, Edwards' and Patau's syndrome. The NIPT examines cell-free DNA in maternal blood. A small proportion of this DNA is of placental origin, but a vast proportion originates from the expectant mother. Findings other than the aforementioned syndromes are considered incidental. Occasionally, maternal malignancy is suspected in asymptomatic women as a result of aberrant NIPT results. In this case series, we present three patients with suspected malignancy based on NIPT results. We recommend the implementation of clinical guidelines for when this situation arises.
Subject(s)
Incidental Findings , Neoplasms/diagnosis , Prenatal Diagnosis/methods , Adult , Female , Humans , Netherlands , Pregnancy , Pregnancy Trimester, FirstABSTRACT
BACKGROUND: Acute graft-versus-host disease (aGVHD) is an important complication of allogeneic stem cell transplantation (alloSCT). High dose glucocorticosteroids, are currently recommended as first-line treatment for grade II-IV aGVHD resulting in overall complete responses (CR) in 40%-50% of patients. No standard second-line regimen has been established. Different options have been reported, including anti-TNFα antibodies. METHODS: We retrospectively reviewed the outcome of 15 patients with steroid-refractory (SR) aGVHD treated with etanercept at our institution. Patients were transplanted for a hematological malignancy and received either a myeloablative or a non-myeloablative conditioning regimen. Prophylaxis of GVHD consisted of cyclosporin A and mycophenolic acid. RESULTS: Acute GVHD was diagnosed at a median of 61 days post-transplantation. All patients had grade III aGVHD of the gut. Second-line treatment with etanercept was started at a median of 13 days after initiation of first-line therapy. Overall response rate was 53%, with CR in 3 patients and PR in 5 patients. Median overall survival after initiation of treatment with etanercept was 66 days (range 5-267) for the entire group. Median overall survival was 99 days (range 47-267 days) for responders and 17 days (range 5-66 days) for non-responders (p<0.01). Nevertheless, all patients died. Causes of death were progressive GVHD in 7 patients (47%), infection in 6 patients (40%), cardiac death in 1 patient (6.7%) and relapse in 1 patient (6,7%). CONCLUSION: Second-line treatment with etanercept does induce responses in SR-aGVHD of the gut but appears to be associated with poor long-term survival even in responding patients.
Subject(s)
Etanercept/therapeutic use , Graft vs Host Disease/drug therapy , Immunosuppressive Agents/therapeutic use , Adult , Aged , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Retrospective Studies , Transplantation Conditioning , Young AdultABSTRACT
A 41-year-old man visited his general practitioner because of upper abdominal pain. Physical examination revealed splenomegaly. Laboratory testing showed pancytopenia with a striking monocytopenia with hairy cells. Immunological and molecular analysis confirmed the diagnosis hairy cell leukemia.
