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1.
Nagoya J Med Sci ; 86(2): 304-313, 2024 May.
Article in English | MEDLINE | ID: mdl-38962412

ABSTRACT

Radiotherapy combined with temozolomide (TMZ+RT) is the primary treatment for high-grade glioma. TMZ is classified as a moderate emetic risk agent and, thus, supportive care for nausea and vomiting is important. In Nagoya University Hospital, all patients are treated with a 5-hydroxy-tryptamine 3 receptor antagonist (5-HT3RA) for the first 3 days. The daily administration of 5-HT3RA is resumed after the 4th day based on the condition of patients during TMZ+RT. Therefore, the present study investigated risk factors for nausea and vomiting in patients requiring the daily administration of 5-HT3RA. Patients with high-grade glioma who received TMZ+RT between January 2014 and December 2019 at our hospital were included. Patients were divided into two groups: a control group (patients who did not resume 5-HT3RA) and resuming 5-HT3RA group (patients who resumed 5-HT3RA after the 4th day), and both groups were compared to identify risk factors for nausea and vomiting during TMZ+RT. There were 78 patients in the control group (68%) and 36 in the resuming 5-HT3RA group (32%). A multivariate analysis of patient backgrounds in the two groups identified age <18 years, PS 2 or more, and occipital lobe tumors as risk factors for nausea and vomiting. Nausea and vomiting were attenuated in 30 patients (83%) in the resuming 5-HT3RA group following the resumption of 5-HT3RA. The results obtained highlight the importance of extracting patients with these risk factors before the initiation of therapy and the early resumption or daily administration of 5-HT3RA according to the condition of each patient.


Subject(s)
Glioma , Nausea , Serotonin 5-HT3 Receptor Antagonists , Temozolomide , Vomiting , Humans , Temozolomide/therapeutic use , Temozolomide/administration & dosage , Temozolomide/adverse effects , Male , Serotonin 5-HT3 Receptor Antagonists/therapeutic use , Serotonin 5-HT3 Receptor Antagonists/administration & dosage , Female , Vomiting/chemically induced , Vomiting/drug therapy , Middle Aged , Glioma/drug therapy , Glioma/radiotherapy , Risk Factors , Aged , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Adult , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Agents, Alkylating/administration & dosage , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods
2.
Clin Transl Sci ; 17(7): e13866, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38965809

ABSTRACT

Rising cure rates in pediatric cancer patients warrants an increased attention toward the long-term consequences of the diagnosis and treatment in survivors. Chemotherapeutic agents can be gonadotoxic, rendering them at risk for infertility post-survival. While semen cryopreservation is an option that can be provided for most (post)pubertal boys before treatment, this is unfortunately not an option prepubertal in age, simply due to the lack of spermatogenesis. Over the last couple of years, studies have thus focused on better understanding the testis niche in response to various chemotherapeutic agents that are commonly administered and their direct and indirect impact on the germ cell populations. These are generally compounds that have a high risk of infertility and have been classified into risk categories in curated fertility guidelines. However, with it comes the lack of evidence and the challenge of using informative models and conditions most reflective of the physiological scenario, in short, the appropriate study designs for clinically relevant outcomes. Besides, the exact mechanism(s) of action for many of these "risk" compounds as well as other agents is unclear. Understanding their behavior and effect on the testis niche will pave the way for incorporating new strategies to ultimately combat infertility. Of the various drug classes, alkylating agents pose the highest risk of gonadotoxicity as per previously established studies as well as risk stratification guidelines. Therefore, this review will summarize the findings in the field of male fertility concerning gonadotoxicity of akylating agents as a result of chemotherapy exposure.


Subject(s)
Antineoplastic Agents, Alkylating , Testis , Humans , Male , Testis/drug effects , Child , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Agents, Alkylating/administration & dosage , Infertility, Male/chemically induced , Infertility, Male/etiology , Infertility, Male/diagnosis , Animals , Spermatogenesis/drug effects , Spermatogenesis/radiation effects , Neoplasms/drug therapy , Puberty/drug effects , Puberty/physiology , Alkylating Agents/adverse effects , Alkylating Agents/administration & dosage
3.
BMC Cancer ; 24(1): 747, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898388

ABSTRACT

BACKGROUND: The prognosis of patients with Relapsed/Refractory Osteosarcoma (R/R OS) remains dismal without an agreement on systemic therapy. The use of High-Dose Ifosfamide (14 g/sqm) with an external pump in outpatient setting (14-IFO) in R/R OS patients is limited. This study represents the first retrospective cohort analysis focused on evaluating the activity and toxicity of 14-IFO in this setting. PATIENTS AND METHODS: The study investigated 14-IFO activity, in terms of tumour response according to RECIST 1.1 criteria, as well as survival rates and toxicity, according to CTCAE v.5. RESULTS: The trial enrolled 26 patients with R/R OS. The Overall Response Rate (ORR) and Disease Control Rate (DCR) obtained was 23% and 57.5%, respectively. Patients with relapsed OS showed a higher ORR (45%) and DCR (82%) compared to refractory patients, irrespective of the number of prior treatment lines received. The achievement of disease control with 14-IFO administration enabled 27% of patients to undergo new local treatment. Four-month Progression-Free Survival (PFS) was 54% for all patients and 82% for the relapsed OS sub-group. Median Overall Survival (OSurv) was 13.7 months, with 1-year OSurv of 51% for all patients and 71% for relapsed patients. Age over 18 years and the presence of refractory disease were identified as negative prognostic factors for this patient cohort. A total of 101 cycles were evaluated for toxic assessment, demonstrating a tolerable profile without grade 3-4 non-haematological toxicities. CONCLUSIONS: 14-IFO should be considered a viable treatment option for R/R OS, particularly due to its well tolerated toxicity profile and the potential for home-administration, which can improve patient quality of life without compromising efficacy.


Subject(s)
Bone Neoplasms , Ifosfamide , Neoplasm Recurrence, Local , Osteosarcoma , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Ifosfamide/therapeutic use , Male , Female , Retrospective Studies , Osteosarcoma/drug therapy , Osteosarcoma/mortality , Osteosarcoma/pathology , Adult , Adolescent , Young Adult , Bone Neoplasms/drug therapy , Bone Neoplasms/mortality , Bone Neoplasms/pathology , Neoplasm Recurrence, Local/drug therapy , Middle Aged , Child , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Alkylating/adverse effects , Neoplasm Grading , Treatment Outcome
4.
Med Oncol ; 41(7): 177, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38884819

ABSTRACT

Treating metastatic malignancies to the central nervous system (CNS) is challenging because many drugs cannot cross the blood-brain-barrier (BBB). Direct intrathecal (IT) drug administration into the cerebrospinal fluid (CSF) is a strategy to overcome this problem. Thiotepa has effective CNS penetration but its popularity has waned over the last two decades due to concerns about its efficacy and potential systemic toxicity. This review evaluates the available evidence for the use of IT thiotepa in hematologic malignancies and non-CNS solid tumors with leptomeningeal disease metastases (LMD). Our search shows that IT thiotepa is a reasonable alternative in hematologic malignancies and LMD due to solid organ malignancies. This suggests a potential role of IT thiotepa in second-or third-line treatment or a substitute role in cases of drug-shortages and adverse effects with other agents. Future research should focus on rigorous comparative trials to establish its definitive role in the evolving landscape of CNS-directed chemotherapy.


Subject(s)
Central Nervous System Neoplasms , Injections, Spinal , Thiotepa , Humans , Thiotepa/administration & dosage , Thiotepa/adverse effects , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/secondary , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Hematologic Neoplasms/drug therapy , Meningeal Neoplasms/drug therapy , Meningeal Neoplasms/secondary
5.
J Neurooncol ; 168(3): 393-404, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38780714

ABSTRACT

PURPOSE: It remains unclear whether combining carmustine wafer (CW) implantation with the standard treatment for adult-type diffuse gliomas is safe and has a prognostic impact. This study aimed to investigate the prognostic value and safety of CW implantation. METHODS: Adult patients with IDH-wild-type and -mutant gliomas, grades 3-4 treated with surgical resection, radiotherapy, and temozolomide chemotherapy between 2013 and 2023 were surveyed. CWs were implanted except in cases of intraoperative wide ventricle opening or marked preoperative brain swelling. For survival analyses, a case-matched dataset based on propensity score matching (PSM), including multiple factors (patient background, diagnosis, and extent of resection) was generated. Progression-free survival (PFS), overall survival (OS), and frequency of complications of CW implantation (brain edema, infection, and cerebrospinal fluid leakage) were compared between the CW and non-use groups. RESULTS: In total, 127 patients (75 in the CW use group and 52 in the non-use group) were enrolled. Regardless of stratification, no significant differences in PFS and OS were observed between the CW use and non-use groups. The frequency of postoperative brain edema was significantly higher in the CW use group than in the non-use group. An adjusted dataset containing 41 patients in the CW use and nonuse groups was generated. Even after PSM, CW implantation had no prognostic effect. CONCLUSIONS: CW implantation with standard treatment demonstrated little beneficial effect for the present strategy of CW use.


Subject(s)
Antineoplastic Agents, Alkylating , Brain Neoplasms , Carmustine , Glioma , Propensity Score , Humans , Male , Female , Carmustine/administration & dosage , Carmustine/adverse effects , Carmustine/therapeutic use , Glioma/drug therapy , Middle Aged , Brain Neoplasms/surgery , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Agents, Alkylating/administration & dosage , Adult , Retrospective Studies , Prognosis , Cohort Studies , Aged , Drug Implants , Survival Rate , Follow-Up Studies
8.
Cancer Med ; 13(10): e7292, 2024 May.
Article in English | MEDLINE | ID: mdl-38752476

ABSTRACT

INTRODUCTION: Type of conditioning regimen impacts the outcome of patients who undergo allogeneic HSCT since graft versus host disease (GVHD), infections, regimen related toxicities (RRT) are important causes of post-transplant mortality. Despite the RRT profile of busulfan, it is frequently used worldwide. Treosulfan has advantages in terms of dose of administration, lower incidence of sinusoidal obstruction syndrome and lower neurotoxicity. We retrospectively investigated outcomes of patients who underwent allogeneic HSCT with treosulfan or busulfan based conditioning regimens in our institution. METHODS: Treosulfan was administered to 94 patients while 85 patients received busulfan. Our outcomes were RRT, chronic and acute GVHD, relapse related mortality (RRM), non-relapse mortality, and fungal infection. The clinical follow up data, regarding the primary and secondary endpoints of our study, of the patients who received treosulfan or busulfan based conditioning regimens were statistically analyzed. RESULTS: The median follow-up was 14 months for the treosulfan group while it was 11 months for the busulfan group (p = 0.16). RRT was 11.7% and 7.1% for treosulfan and busulfan respectively. The incidence of extensive chronic GVHD was less frequent in the treosulfan group compared to the busulfan group (15.7% vs. 32.1%) (p < 0.001). The incidence of acute GVHD (Grade 3 or higher) was 32.2% in the treosulfan group while it was 31.6% in the busulfan group. The RRM was 17% in the treosulfan group while it was 34% in the busulfan group. The non-relapse mortality was 35.5% and 29.4% in the treosulfan group and in the busulfan group respectively (p = 0.962). CONCLUSION: Treosulfan, with a lower RRM, lower chronic GVHD incidence and with a similar RRT profile appears to be a safe alternative to busulfan.


Subject(s)
Busulfan , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Transplantation Conditioning , Transplantation, Homologous , Humans , Busulfan/analogs & derivatives , Busulfan/therapeutic use , Busulfan/adverse effects , Busulfan/administration & dosage , Transplantation Conditioning/methods , Female , Male , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Adult , Middle Aged , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Graft vs Host Disease/epidemiology , Retrospective Studies , Young Adult , Adolescent , Treatment Outcome , Aged , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Alkylating/adverse effects
9.
Pediatr Blood Cancer ; 71(7): e31004, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38637875

ABSTRACT

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial pneumonia with distinct clinicopathologic features. It has been associated with exposure to hematopoietic stem cell transplantation (HSCT) and classical alkylating agents. Here, we highlight PPFE as a late complication of childhood cancer therapy by describing the cases of four survivors of childhood cancer with a diagnosis of treatment-related PPFE. All patients received high-dose alkylating agents. PPFE should be considered in the differential diagnosis of restrictive lung disease in patients with history of exposure to alkylating agents or HSCT. Development of PPFE-specific, noninvasive diagnostic tools and disease-modifying therapies will clinically benefit these patients.


Subject(s)
Lung Diseases, Interstitial , Humans , Male , Female , Child , Adolescent , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/chemically induced , Lung Diseases, Interstitial/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Neoplasms/drug therapy , Neoplasms/complications , Neoplasms/pathology , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/pathology , Child, Preschool , Antineoplastic Agents, Alkylating/adverse effects
10.
J Cancer Res Clin Oncol ; 150(4): 212, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662247

ABSTRACT

BACKGROUND AND AIM: Morinda citrifolia fruit juice (noni) is an herbal remedy documented to have antioxidant properties. It has been suggested that prevention of carcinogen-DNA adduct formation and the antioxidant activity of NJ may contribute to the cancer preventive effect. In the present study, the antitumor activity of noni was investigated in the presence of cyclophosphamide (CYL) in vitro and in vivo. METHODS: In vitro breast cancer cells (MDA-MB-468) were used to measure the percentage of inhibition and the IC50. The in vivo antitumor activity of noni was studied by monitoring the mean survival time (MST), percentage increase in life span (%ILS), viable and non-viable cell count, tumor volume, body weight, and hematological and serum biochemical parameters in mice. Treatment with noni and CYL exhibited dose- and time-dependent cytotoxicity toward breast cancer cells. RESULTS: Individual treatment of noni and CYL exhibited dose- and time-dependent cytotoxicity on breast cancer cell lines, while in combination therapy of noni and CYL, noni enhances cytotoxic effect of CYL at 48 h than that at 24 h. Similar result was found in in vivo studies, the results of which revealed that alone treatment of CYL and noni suppressed tumor growth. However, combination treatment with CYL and noni presented better tumor inhibition than that of alone treatment of CYL and noni. On the contrary, CYL alone drastically attenuated hematological parameters, i.e., RBC, WBC, and Hb compared to normal and control groups, and this change was reversed and normalized by noni when given as combination therapy with CYL. Moreover, the levels of serum biochemical markers, i.e., AST, ALP, and ALT, were significantly increased in the control and CYL-treated groups than those in the normal group. In the combination treatment of noni and CYL, the above biochemical marker levels significantly decreased compared to CYL alone-treated group. CONCLUSIONS: The present study suggested that CYL treatment can cause serious myelotoxicity and hepatic injury in cancer patients. In conclusion, the combined use of noni with CYL potentially enhances the antitumor activity of CYL and suppresses myelotoxicity and hepatotoxicity induced by CYL in tumor-bearing mice.


Subject(s)
Breast Neoplasms , Cyclophosphamide , Morinda , Animals , Cyclophosphamide/pharmacology , Cyclophosphamide/adverse effects , Mice , Humans , Female , Morinda/chemistry , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Fruit and Vegetable Juices , Xenograft Model Antitumor Assays , Drug Synergism , Plant Extracts/pharmacology , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Agents, Alkylating/pharmacology , Antineoplastic Agents, Alkylating/adverse effects , Mice, Inbred BALB C , Chemical and Drug Induced Liver Injury/prevention & control , Chemical and Drug Induced Liver Injury/etiology
11.
J Hematol Oncol ; 17(1): 19, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38644469

ABSTRACT

Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. However, bendamustine as lymphodepletion prior to lisocabtagene maraleucel (liso-cel), a 4-1BB co-stimulated, fixed CD4:CD8 ratio anti-CD19 CART product, has not been described yet. Thus, we studied a cohort of sequentially-treated patients with large B-cell lymphomas who received bendamustine lymphodepletion before liso-cel at the University of Pennsylvania between 5/2021 and 12/2023 (n = 31). Patients were evaluated for toxicities and responses. Of note, 7 patients (22.6%) would have dnot met the inclusion criteria for the registrational liso-cel clinical trials, mostly due to older age. Overall and complete response rates were 76.9% and 73.1%, respectively. At a median follow-up of 6.3 months, the 6-month progression-free and overall survival were 59.9% and 91.1%, respectively. Rates of cytokine-release syndrome (CRS) and neurotoxicity (ICANS) of any grade were 9.7% and 9.7%, respectively, with no grade ≥ 3 events. No infections were reported during the first 30 days following liso-cel infusion. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.


Subject(s)
Bendamustine Hydrochloride , Immunotherapy, Adoptive , Humans , Bendamustine Hydrochloride/therapeutic use , Middle Aged , Male , Female , Aged , Immunotherapy, Adoptive/methods , Immunotherapy, Adoptive/adverse effects , Retrospective Studies , Adult , Lymphoma, Large B-Cell, Diffuse/drug therapy , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Alkylating/adverse effects , Biological Products/therapeutic use , Biological Products/adverse effects , Aged, 80 and over , Treatment Outcome
13.
Int J Mol Sci ; 25(6)2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38542190

ABSTRACT

A glioblastoma (GBM) is one of the most aggressive, infiltrative, and treatment-resistant malignancies of the central nervous system (CNS). The current standard of care for GBMs include maximally safe tumor resection, followed by concurrent adjuvant radiation treatment and chemotherapy with the DNA alkylating agent temozolomide (TMZ), which was approved by the FDA in 2005 based on a marginal increase (~2 months) in overall survival (OS) levels. This treatment approach, while initially successful in containing and treating GBM, almost invariably fails to prevent tumor recurrence. In addition to the limited therapeutic benefit, TMZ also causes debilitating adverse events (AEs) that significantly impact the quality of life of GBM patients. Some of the most common AEs include hematologic (e.g., thrombocytopenia, neutropenia, anemia) and non-hematologic (e.g., nausea, vomiting, constipation, dizziness) toxicities. Recurrent GBMs are often resistant to TMZ and other DNA-damaging agents. Thus, there is an urgent need to devise strategies to potentiate TMZ activity, to overcome drug resistance, and to reduce dose-dependent AEs. Here, we analyze major mechanisms of the TMZ resistance-mediated intracellular signaling activation of DNA repair pathways and the overexpression of drug transporters. We review some of the approaches investigated to counteract these mechanisms of resistance to TMZ, including the use of chemosensitizers and drug delivery strategies to enhance tumoral drug exposure.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Temozolomide/pharmacology , Temozolomide/therapeutic use , Glioblastoma/metabolism , Antineoplastic Agents, Alkylating/adverse effects , Quality of Life , Brain Neoplasms/pathology , Neoplasm Recurrence, Local/drug therapy , DNA/pharmacology , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor
14.
J Clin Oncol ; 42(13): 1488-1498, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38315944

ABSTRACT

PURPOSE: Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting BRCA mutation and/or BRCAness phenotype. METHODS: A prospective, open-label, randomized phase III MITO-23 trial evaluated the activity and safety of trabectedin 1.3 mg/m2 given once every 3 weeks (arm A) in BRCA 1/2 mutation carriers or patients with BRCAness phenotype (ie, patients who responded to ≥two previous platinum-based treatments) with recurrent OC, primary peritoneal carcinoma, or fallopian tube cancer in comparison with physician's choice chemotherapy in the control arm (arm B; pegylated liposomal doxorubicin, topotecan, gemcitabine, once-weekly paclitaxel, or carboplatin). The primary end point was overall survival (OS) evaluated in the intention-to-treat population. RESULTS: Overall, 244 patients from 21 MITO centers were randomly assigned (arm A = 122/arm B = 122). More than 70% of patients received ≥three previous chemotherapy lines and 35.7% had received a poly (ADP-ribose) polymerase inhibitor (PARPi) before enrollment. Median OS was not significantly different between the arms: arm A: 15.8 versus arm B: 17.9 months (P = .304). Median progression-free survival was 4.9 months in arm A versus 4.4 months in arm B (P = .897). Among 208 patients evaluable for efficacy, the objective response rate was 17.1% in arm A and 21.4% in arm B, with comparable median duration of response (5.62 v 5.66 months, respectively). No superior effect was observed for trabectedin in the prespecified subgroup analyses according to BRCA mutational status, chemotherapy type, and pretreatment with a PARPi and/or platinum-free interval. Trabectedin showed a higher frequency of grade ≥3 adverse events (AEs), serious AEs, and serious adverse drug reactions compared with control chemotherapy. CONCLUSION: Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.


Subject(s)
Mutation , Neoplasm Recurrence, Local , Ovarian Neoplasms , Trabectedin , Humans , Female , Trabectedin/therapeutic use , Trabectedin/administration & dosage , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Aged , Adult , Neoplasm Recurrence, Local/drug therapy , Phenotype , Prospective Studies , BRCA2 Protein/genetics , BRCA1 Protein/genetics , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Aged, 80 and over , Progression-Free Survival
15.
Expert Rev Anticancer Ther ; 24(1-2): 5-14, 2024.
Article in English | MEDLINE | ID: mdl-38031874

ABSTRACT

INTRODUCTION: Ifosfamide is an alkylating chemotherapeutic agent used in the treatment of various neoplasms. Its main adverse effects include renal damage. AREAS COVERED: A comprehensive review was conducted, including 100 articles from the Scielo, Scopus, and EMBASE databases. Ifosfamide-induced nephrotoxicity is attributed to its toxic metabolites, such as acrolein and chloroacetaldehyde, which cause mitochondrial damage and oxidative stress in renal tubular cells. Literature review found a 29-year average age with no gender predominance and a mortality of 13%. Currently, no fully effective strategy exists for preventing ifosfamide-induced nephrotoxicity; however, hydration, forced diuresis, and other interventions are employed to limit renal damage. Long-term renal function monitoring is essential for patients treated with ifosfamide. EXPERT OPINION: Ifosfamide remains essential in neoplasm treatment, but nephrotoxicity, often compounded by coadministered drugs, poses diagnostic challenges. Preventive strategies are lacking, necessitating further research. Identifying timely risk factors can mitigate renal damage, and a multidisciplinary approach manages established nephrotoxicity. Emerging therapies may reduce ifosfamide induced nephrotoxicity.


Ifosfamide is a type of chemotherapy used to treat different types of cancers. However, one of its main side effects is kidney damage. Researchers reviewed 100 articles from medical databases to understand how ifosfamide affects the kidneys. The kidney damage is caused by harmful substances produced when ifosfamide is broken down in the body. These substances can harm the cells in the kidneys. Studies have shown that 13% of the patients treated with ifosfamide can die. Currently, there is no perfect way to prevent kidney damage from ifosfamide, but doctors try to protect the kidneys by giving patients plenty of fluids and using other treatments, so it's important for patients who receive ifosfamide to have their kidney function checked regularly. Although ifosfamide is effective against cancer, its potential kidney side effects should be carefully considered by doctors when deciding on the best treatment for each patient.


Subject(s)
Antineoplastic Agents, Alkylating , Ifosfamide , Humans , Ifosfamide/adverse effects , Antineoplastic Agents, Alkylating/adverse effects , Kidney
16.
J Neurooncol ; 166(3): 407-415, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38153582

ABSTRACT

PURPOSE: The optimal duration of post-radiation temozolomide in newly diagnosed glioblastoma remains unclear, with no published phase III randomised trials. Standard-of-care stipulates 6 months. However, in routine care, it is often extended to 12 months, despite lacking robust supporting data. METHODS: GEINO14-01 (Spain) and EX-TEM (Australia) studies enrolled glioblastoma patients without progression at the end of 6 months post-radiation temozolomide. Participants were randomised 1:1 to six additional months of temozolomide or observation. Primary endpoint was 6-month progression free survival from date of randomisation (6mPFS). Secondary endpoints included overall survival (OS) and toxicity. 204 patients were required to detect an improvement in 6mPFS from 50 to 60% (80% power). Neither study recruited sufficient patients. We performed a combined analysis of individual patient data. RESULTS: 205 patients were recruited: 159 in GEINO14-01 (2014-2018) and 46 in EX-TEM (2019-2022). Median follow-up was 20.0 and 14.5 months. Baseline characteristics were balanced. There was no significant improvement in 6mPFS (57.2% vs 64.0%, OR0.75, p = 0.4), nor across any subgroups, including MGMT methylated; PFS (HR0.92, p = 0.59, median 7.8 vs 9.7 months); or OS (HR1.03, p = 0.87, median 20.1 vs 19.4 months). During treatment extension, 64% experienced any grade adverse event, mainly fatigue and gastrointestinal (both 54%). Only a minority required treatment changes: 4.5% dose delay, 7.5% dose reduction, 1.5% temozolomide discontinuation. CONCLUSION: For glioblastoma patients, extending post-radiation temozolomide from 6 to 12 months is well tolerated but does not improve 6mPFS. We could not identify any subset that benefitted from extended treatment. Six months should remain standard-of-care.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Temozolomide/therapeutic use , Glioblastoma/drug therapy , Glioblastoma/radiotherapy , Prospective Studies , Dacarbazine/adverse effects , Disease-Free Survival , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Antineoplastic Agents, Alkylating/adverse effects
17.
J Neurooncol ; 165(3): 561-568, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38108984

ABSTRACT

PURPOSE: starting from a lack of precise and coherent data in literature, aim of this work is to retrospectively study the influence of chemotherapy with Temozolomide (TMZ) on a wide series of neuropsychological functions in a population of adult high-grade glioma patients. METHODS: an extensive neuropsychological battery was administered pre-operatively (T0) and after 6 (T1) and 12 months (T2) from surgery. After full recovery from surgery, TMZ was delivered concomitant to radiotherapy and, subsequently, adjuvantly for 5-day cycles per month. Parametric and non-parametric analyses were conducted to verify the influence of several aspects of chemotherapy on the adjusted scores of each cognitive test at the two post-operative follow-ups. RESULTS: Sixty-one patients were included at T0; patients with a lower adjuvant TMZ dosage reported a better performance at the visual attention test at T1, and at the deductive reasoning test at T2. Undergoing more than 8 cycles of adjuvant therapy was slightly associated with a better performance at the long-term verbal memory tasks at T2. No other associations were found with the other cognitive tests and autonomy scales administered. CONCLUSIONS: TMZ proved to be a secure treatment with no negative side effects on cognition and on level of daily autonomy, even at the highest dosage used. This is a positive finding which enables clinicians to reassure patients about the absence of significant negative effects of TMZ on their daily life functioning. In this view, eventual cognitive changes during treatment might not be attributed to chemotherapy but to other events such as tumour relapse.


Subject(s)
Brain Neoplasms , Glioma , Adult , Humans , Temozolomide/therapeutic use , Retrospective Studies , Dacarbazine/adverse effects , Brain Neoplasms/pathology , Neoplasm Recurrence, Local/drug therapy , Glioma/pathology , Antineoplastic Agents, Alkylating/adverse effects
18.
Int J Circumpolar Health ; 82(1): 2285077, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37992407

ABSTRACT

Glioblastoma (GBM), WHO grade IV, is the most common primary malignant brain tumour among adults with a devastating overall survival of 14-22 months. Standard treatment of GBM includes maximum safe resection, radiotherapy plus concomitant and adjuvant temozolomide (TMZ), given over a period of approximately 9 months. Treatment and follow-up for Greenlandic patients with GBM are managed at Rigshospitalet (RH), Copenhagen. Greenlandic GBM patients, therefore, travel back and forth to RH, often unaccompanied, and challenged by cognitive failure or other symptoms from their disease and/or treatment. Few Greenlandic patients are diagnosed with GBM annually, but considering the poor prognosis and short remaining lifespan, it would be preferable to limit their travels. TMZ is administrated as capsules. Health personnel at Queen Ingrid's Hospital (DIH), Nuuk, are trained in treating other oncological diseases and handling side effects. Hence, it could be investigated whether administration of adjuvant TMZ at DIH could be feasible after personnel education as well as economic consideration and compensation, in close collaboration with neuro oncologists at RH. In this article, we describe the Greenlandic cancer treatment, and the typical workflow from diagnosis of GBM to treatment to progression.


Subject(s)
Brain Neoplasms , Glioblastoma , Adult , Humans , Glioblastoma/drug therapy , Glioblastoma/pathology , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Alkylating/adverse effects , Dacarbazine/therapeutic use , Dacarbazine/adverse effects , Chemotherapy, Adjuvant , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Temozolomide/therapeutic use
19.
Rom J Ophthalmol ; 67(3): 305-308, 2023.
Article in English | MEDLINE | ID: mdl-37876503

ABSTRACT

Objective: Description of melphalan's toxicity in retinoblastoma treatment. Methods: Clinical case report. Results: We presented a case of unilateral retinoblastoma with vitreous seeding at diagnosis, in which the use of intravitreal melphalan produced many adverse reactions. Conclusions: Vitreous seedings have been one of the most important challenges in retinoblastoma treatment. Intravitreal melphalan has achieved the regression of vitreous seedings in a large percentage of cases. It is a safe treatment; however, it can produce toxicity, even with the standard dose of 20-30 µg, which has been poorly documented. Exhaustive follow-up of patients is recommended for an early diagnosis of possible adverse effects. Abbreviations: OS = left eye, RI = magnetic resonance imaging, OCT = optical coherence tomography.


Subject(s)
Retinal Neoplasms , Retinoblastoma , Humans , Retinoblastoma/diagnosis , Retinoblastoma/drug therapy , Melphalan/adverse effects , Retinal Neoplasms/diagnosis , Retinal Neoplasms/drug therapy , Antineoplastic Agents, Alkylating/adverse effects , Retrospective Studies , Vitreous Body , Intravitreal Injections , Neoplasm Seeding
20.
J Cancer Res Ther ; 19(5): 1126-1130, 2023.
Article in English | MEDLINE | ID: mdl-37787273

ABSTRACT

Purpose: To assess the treatment response and toxicity profile among two groups of newly diagnosed glioblastoma multiforme (GBM) postoperative patients receiving conventional radiotherapy (RT) versus hypofractionated RT with concurrent temozolomide (TMZ) in both. Materials and Methods: A total of 50 patients randomly allotted into two arms (25 in each). Dose received 60 Gy (2 Gy/#) in conventional fractionation RT versus 50 Gy (2.5 Gy/#) in hypofractionated RT with concurrent TMZ 75 mg/m2 orally daily in both arms, respectively. Follow-up was done at 1, 3, 6, and 12 months after completion of treatment to evaluate toxicities, treatment response, and progression-free survival (PFS). Results: All patients were well tolerated with treatment; no major adverse effects were monitored in two arms. There was no statistical significant difference in treatment response, which was found 64% versus 60% in arm A and arm B, respectively, at 3 months of follow-up (P = 0.768). Toxicity profiles were also noted similar in both arms. The 6-month PFS was 84% and 80% in arm A and arm B, respectively (P = 0.71) and 12-month PFS was 60% and 52% in arm A and arm B, respectively (P = 0.69). Conclusion: Among the patients followed, this study showed that hypofractionated RT regimen was not inferior to conventional RT regimen.


Subject(s)
Brain Neoplasms , Glioblastoma , Humans , Antineoplastic Agents, Alkylating/adverse effects , Brain Neoplasms/therapy , Brain Neoplasms/drug therapy , Chemoradiotherapy/adverse effects , Glioblastoma/therapy , Glioblastoma/drug therapy , Temozolomide/adverse effects
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