Enhancing Effect on Tumour Apoptosis With the Use of Pentoxifylline in Patients With Hodgkin Lymphoma
Status:
Recruiting
Trial end date:
2024-07-01
Target enrollment:
Participant gender:
Summary
Hodgkin's Lymphoma (HL) is a neoplasm that affects the lymph nodes and the lymphatic system.
In Mexico, HL is the seventh most incident cancer and the ninth with the highest mortality.
It is characterized by the presence of Reed-Sternberg (HRS) cells derived from B cells of the
germinal center. They harbor mutations that activate the NF-κB pathway, favoring cell
survival and their reprogram. Currently, the available therapeutic options are chemotherapy
and radiotherapy, achieving cure rates of 75% in patients in advanced stages, in which 70% of
these are found at the time of diagnosis. The investigators proposed the use of
pentoxifylline (PTX) as a therapeutic option to enhance the antitumor effect generated by the
treatment, since it can increases the efficacy of apoptosis, in vitro and in vivo, induced by
doxorubicin, cisplatin, and adriamycin in human leukemic and cervical cancer cells, through
inhibition of NF-κB by preventing phosphorylation of serine 32 of the inhibitor κB; it also
decreases the expression of Bcl-2 and Bcl-XL, induces the release of cytochrome c and
caspases 3, 9, and cleavage of caspase 8. The investigators evaluated the effects of PTX
during the steroid window phase at induction to remission in pediatric patients with LLA of a
recent diagnosis, where it was shown that the combined treatment of prednisone (PRD) with PTX
achieves greater percentages of apoptosis compared to individual treatment. In addition, the
effect of PTX on the expression of genes associated with apoptosis was evaluated; where it
was shown that activates the intrinsic and extrinsic pathways of apoptosis. Fortilin is a
protein whose serum levels increase 2.4 times more after treatment with chemotherapy or
radiotherapy in patients with malignancies, so it is considered a specific and sensitive
biomarker of early apoptosis in vivo. The present protocol will evaluate the enhancing effect
of PTX on tumor apoptosis in combination with chemotherapeutical agents in pediatric and AYA
patients with HL. Apoptosis will be measured in vivo by quantifying serum levels of fortilin
and cytochrome c in participants before and after treatment by ELISA; as well as an
evaluation of the clinical response based on the results of the PET-Scan, overall and
event-free survival according to the Kaplan-Meier curves, and the adverse effects associated
with the use of PTX according to the common terminology criteria for adverse events and
causality algorithms.