Abstract
Abstract 5112 BackgroundPharmacological induction of fetal hemoglobin (Hb F) can benefit patients with beta-hemoglobinopathies. Hydroxyurea (HU) is the drug most commonly used to induce Hb F. HU is converted to a free radical scavenger in vivo and inhibits the R2 subunit of ribonucleotide reductase. When used in the treatment of myeloproliferative syndromes, HU has been described to increase Hb F in people without hemoglobinopathies (Alter et al, Blood 66(2) 373-5). Gemcitabine is a nucleoside analog chemotherapeutic that inhibits the large R1 subunit of ribonucleotide reductase. We hypothesized that like HU, gemcitabine treatment would cause Hb F percentage to rise. Though oncology patients are a distinct population, gemcitabine induction of Hb F during the treatment of cancer would suggest a potential role for gemcitabine in the management of beta-hemoglobinopathies such as sickle cell disease and beta-thalassemia. MethodsParticipants for this prospective observational cohort study were recruited from the Moores UCSD Cancer Center upon documentation of a cancer diagnosis and oncologist-initiated plans for treatment with single agent gemcitabine. Enrolled subjects were gemcitabine naïve and had not received any chemotherapy for the preceding 4 weeks. Serum Hb F was quantified by electrophoresis prior to each of the first 4 gemcitabine treatments. All other laboratory evaluation was standard-of-care. The primary objective was to assess changes in Hb F among cancer patients in response to their initial 3 treatments with gemcitabine. Enrollment was halted early given the absence of a substantial treatment effect among the first 6 subjects. ResultsSix subjects were eligible. Three were men. Five were Caucasian and one was an Asian/Pacific Islander. All subjects received gemcitabine monotherapy for the treatment of adenocarcinoma of the pancreas or breast at a weekly dose of 1000 mg/m2. Baseline Hb F range was 0 – 1.0%. Four of the six subjects (three women, one man; all Caucasian) experienced no change in Hb F from baseline to the final measurement. Two subjects experienced a 0.4% increase in Hb F from baseline to the final measurement 4 weeks later. Final Hb F range was 0 – 1.4%. ConclusionsWe found that gemcitabine monotherapy for the treatment of cancer did not induce Hb F in this small study cohort. Gemcitabine may lack this ability. Alternative explanations for the absence of clinically meaningful Hb F induction include the small population studied, differences between oncology patients and the general population, short duration of treatment, and intermittent dosing of gemcitabine. DisclosuresNo relevant conflicts of interest to declare.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.