ABSTRACT
TKIs long-term treatment in CML may lead to persistent adverse events (AEs) that can promote relevant morbidity and mortality. Consequently, TKIs dose reduction is often used to prevent AEs. However, data on its impact on successful treatment-free remission (TFR) are quite scarce. We conducted a retrospective study on the outcome of CML subjects who discontinued low-dose TKIs from 54 Italian hematology centers participating in the Campus CML network. Overall, 1.785 of 5.108 (35.0%) regularly followed CML patients were treated with low-dose TKIs, more frequently due to relevant comorbidities or AEs (1.288, 72.2%). TFR was attempted in 248 (13.9%) subjects, all but three while in deep molecular response (DMR). After a median follow-up of 24.9 months, 172 (69.4%) patients were still in TFR. TFR outcome was not influenced by gender, Sokal/ELTS risk scores, prior interferon, number and last type of TKI used prior to treatment cessation, DMR degree, reason for dose reduction or median TKIs duration. Conversely, TFR probability was significantly better in the absence of resistance to any prior TKI. In addition, patients with a longer DMR duration before TKI discontinuation (i.e., >6.8 years) and those with an e14a2 BCR::ABL1 transcript type showed a trend towards prolonged TFR. It should also be emphasized that only 30.6% of our cases suffered from molecular relapse, less than reported during full-dose TKI treatment. The use of low-dose TKIs does not appear to affect the likelihood of achieving a DMR and thus trying a treatment withdrawal, but might even promote the TFR rate.
ABSTRACT
The treatment of glioblastoma (GBM) is a challenge for the biomedical research since cures remain elusive. Its current therapy, consisted on surgery, radiotherapy, and concomitant chemotherapy with temozolomide (TMZ), is often uneffective. Here, we proposed the use of zoledronic acid (ZOL) as a potential agent for the treatment of GBM. Our group previously developed self-assembling nanoparticles, also named PLCaPZ NPs, to use ZOL in the treatment of prostate cancer. Here, we updated the previously developed nanoparticles (NPs) by designing transferrin (Tf)-targeted self-assembling NPs, also named Tf-PLCaPZ NPs, to use ZOL in the treatment of brain tumors, e.g., GBM. The efficacy of Tf-PLCaPZ NPs was evaluated in different GBM cell lines and in an animal model of GBM, in comparison with PLCaPZ NPs and free ZOL. Tf-PLCaPZ NPs were characterized by a narrow size distribution and a high incorporation efficiency of ZOL. Moreover, the presence of Tf significantly reduced the hemolytic activity of the formulation. In vitro, in LN229 cells, a significant uptake and cell growth inhibition after treatment with Tf-PLCaPZ NPs was achieved. Moreover, the sequential therapy of TMZ and Tf-PLCaPZ NPs lead to a superior therapeutic activity compared to their single administration. The results obtained in mice xenografted with U373MG, revealed a significant anticancer activity of Tf-PLCaPZ NPs, while the tumors remained unaffected with free TMZ. These promising results introduce a novel type of easy-to-obtain NPs for the delivery of ZOL in the treatment of GBM tumors.
Subject(s)
Diphosphonates/administration & dosage , Glioblastoma/therapy , Imidazoles/administration & dosage , Nanocapsules/chemistry , Receptors, Transferrin/metabolism , Transferrin/metabolism , Transferrin/pharmacokinetics , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Diffusion , Diphosphonates/chemistry , Glioblastoma/pathology , Imidazoles/chemistry , Male , Mice , Mice, Nude , Molecular Targeted Therapy/methods , Nanocapsules/ultrastructure , Transferrin/chemistry , Treatment Outcome , Zoledronic AcidSubject(s)
Lung Neoplasms/surgery , Respiratory Mechanics , Aged , Female , Follow-Up Studies , Humans , Male , Mathematics , Middle Aged , Postoperative Period , Preoperative CareABSTRACT
A case of pheochromocytoma observed in a 31-year old woman at the sixth month of pregnancy is reported. The treatment was successful for both the mother and fetus. Oral phenoxybenzamine has allowed most favourable pressure control and completion of pregnancy at term with cesarean section and tumor resection performed at the same time. The prognostic role of early diagnosis is stressed and the therapeutic problems posed by this rare association at high maternal and fetal risk, are discussed.
