Paclitaxel is metabolized, and putative metabolic products can be found in plasma of patients treated with the drug. Our results indicate that myelosuppression can be predicted by the measurement of the duration of plasma concentrations above the threshold of 0.1 mumol/L.
Background
Cancer patients are at higher risk of developing severe COVID-19. However, safety and efficacy of COVID-19 vaccination in cancer patients undergoing treatment is unclear.
Patients and Methods
In this interventional prospective multi-cohort study, priming and booster doses of the BNT162b2 COVID-19 vaccine were administered 21 days apart to solid tumor patients receiving chemotherapy, immunotherapy, targeted- or hormonal therapy, and patients with a hematologic malignancy receiving rituximab or after allogeneic hematopoietic stem cell transplantation. Vaccine safety and efficacy (until three months post-booster) were assessed. Anti-SARS-CoV-2 receptor binding domain (RBD) antibody levels were followed over time (until 28 days post-booster) and
in vitro
SARS-CoV-2 50% neutralization titers (NT50) towards the wild-type Wuhan strain were analyzed 28 days post-booster.
Results
Local and systemic adverse events (AEs) were mostly mild to moderate (only 1-3% of patients experiencing severe AEs). Local, but not systemic, AEs occurred more frequently after booster dose. 28 days post-booster vaccination of 197 cancer patients, RBD-binding antibody titers and NT50 were lower in the chemotherapy group (234.05IU/mL [95%CI 122.10-448.66] and NT50 of 24.54 [95% CI 14.50-41.52]) compared to healthy individuals (1844.93IU/mL [95% CI 1383.57-2460.14] and NT50 of 122.63 [95% CI 76.85-195.67]), irrespective of timing of vaccination during chemotherapy cycles. Extremely low antibody responses were seen in hematology patients receiving rituximab, only two patients had RBD-binding antibody titers necessary for 50% protection against symptomatic SARS-CoV-2 infection (<200IU/mL) and only one had NT50 above the limit of detection. During the study period, five cancer patients tested positive for SARS-CoV-2 infection, including a case of severe COVID-19 in a patient receiving rituximab, resulting in a 2-week hospital admission.
conclusion
The BNT162b2 vaccine is well-tolerated in cancer patients under active treatment. However, the antibody response of immunized cancer patients was delayed and diminished, mainly in patients receiving chemotherapy or rituximab, resulting in breakthrough infections.
Taxanes belong to a new group of antineoplastic agents with a novel mechanism of action for a cytotoxic drug. They promote microtubule assembly and stabilize the microtubules. Paclitaxel, the first agent in this group to become available, was isolated from the Pacific yew, Taxus brevifolia, in 1971. In preclinical and clinical studies, paclitaxel and its semisynthetic analog docetaxel exhibit significant antitumor activity. This review deals with the physicochemical properties, pharmacology, and results of preclinical and clinical trials of the taxanes.
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