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Veterinary and Comparative Oncology Sep 2022Orally administered daily chemotherapy offers a novel treatment approach for canine lymphoma in a population of dogs that have failed or not tolerated maximum tolerable...
Orally administered daily chemotherapy offers a novel treatment approach for canine lymphoma in a population of dogs that have failed or not tolerated maximum tolerable dose chemotherapy. A multidrug oral chemotherapy protocol was designed and implemented for the treatment of 50 dogs with multicentric lymphoma with minimal side effects. The protocol consisted of oral procarbazine, prednisolone and cyclophosphamide (PPC) administered daily. Efficacy and toxicity were evaluated by clinical and laboratory evaluation. An overall response rate of 70% was achieved, with 24% and 46% of dogs having a partial and complete response, respectively, to treatment with the PPC protocol. Response to the PPC protocol (complete or partial) and age were the only factors identified as prognostic for time from initiation of the PPC chemotherapy until death. Overall, the protocol was very well tolerated with only one dog requiring protocol discontinuation due to grade 4 thrombocytopenia. Eight dogs recorded gastrointestinal toxicities, seven grade I and one grade II toxicity. These findings demonstrate that the administration of a continuous oral combination chemotherapy can provide comparable survival times in the rescue setting in dogs with multicentric lymphoma with minimal side effects.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dog Diseases; Dogs; Doxorubicin; Lymphoma; Prednisolone; Procarbazine; Treatment Outcome; Vincristine
PubMed: 35338560
DOI: 10.1111/vco.12814 -
Child's Nervous System : ChNS :... May 2024Pediatric low-grade gliomas (PLGG) are commonly treated with a combination of surgery, radiotherapy, and chemotherapy. Recent trends prioritize reducing long-term...
Pediatric low-grade gliomas (PLGG) are commonly treated with a combination of surgery, radiotherapy, and chemotherapy. Recent trends prioritize reducing long-term morbidities, particularly in younger patients. While historically chemotherapy was reserved for cases progressing after radiotherapy, evolving recommendations now advocate for its early use, particularly in younger age groups. The carboplatin and vincristine (CV) combination stands as a standard systemic therapy for PLGG, varying in dosage and administration between North America and Europe. Clinical trials have shown promising response rates, albeit with varying toxicity profiles. Vinblastine has emerged as another effective regimen with minimal toxicity. TPCV, a regimen combining thioguanine, procarbazine, lomustine, and vincristine, was compared to CV in a Children's Oncology Group trial, showing comparable outcomes, but more toxicity. Vinorelbine, temozolomide, and metronomic chemotherapy have also been explored, with varied success rates and toxicity profiles. Around 40-50% of PLGG patients require subsequent chemotherapy lines. Studies have shown varied efficacy in subsequent lines, with NF1 patients generally exhibiting better outcomes. The identification of molecular drivers like BRAF mutations has led to targeted therapies' development, showing promise in specific molecular subgroups. Trials comparing targeted therapy to conventional chemotherapy aim to delineate optimal treatment strategies based on molecular profiles. The landscape of chemotherapy in PLGG is evolving, with a growing focus on molecular subtyping and targeted therapies. Understanding the role of chemotherapy in conjunction with novel treatments is crucial for optimizing outcomes in pediatric patients with low-grade gliomas.
PubMed: 38819670
DOI: 10.1007/s00381-024-06458-w -
Clinical Lymphoma, Myeloma & Leukemia Nov 2022Chemotherapy for classic Hodgkin lymphoma (cHL) patients on hemodialysis (HD) is an extremely challenging situation because pharmacokinetic and pharmacodynamic studies... (Review)
Review
Chemotherapy for classic Hodgkin lymphoma (cHL) patients on hemodialysis (HD) is an extremely challenging situation because pharmacokinetic and pharmacodynamic studies of most chemotherapeutics are lacking for the HD patient, and the small amount of evidence available comes mostly from case reports and small case series. In this review, we provide recommendations based on treatment experience of cHL patients on HD in the literature. HD patients undergoing chemotherapy are at risk of overdose and toxicities because many drugs are significantly eliminated by the kidneys, and at the same time, are at risk of undertreatment because many drugs are removed by HD. Therefore, dose modifications and timing of drug administration in relation to HD sessions must be carefully planned according to the distinct traits of each chemotherapeutic. We carried out an exhaustive literature review of reports of actual administrations of chemotherapeutics to cHL on HD, and also extrapolated data from reports of the same chemotherapeutics that were administered to HD patients with malignancies other than cHL. We summarized the information found in the literature, and provide practical and balanced recommendations concerning dose modifications and optimal timing of drug administration in relation to HD sessions for each chemotherapeutic. Chemotherapy regimens and individual chemotherapeutics studied in this review include ABVD (doxorubicin + bleomycin + vinblastine + dacarbazine), BEACOPP (bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisolone), MOPP (mechlorethamine + vincristine + procarbazine + prednisolone), gemcitabine, vinorelbine, brentuximab vedotin, and PD-1 inhibitors (nivolumab and pembrolizumab).
Topics: Humans; Hodgkin Disease; Vinblastine; Vincristine; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Brentuximab Vedotin; Mechlorethamine; Procarbazine; Vinorelbine; Nivolumab; Immune Checkpoint Inhibitors; Bleomycin; Dacarbazine; Doxorubicin; Cyclophosphamide; Prednisolone; Renal Dialysis
PubMed: 35948477
DOI: 10.1016/j.clml.2022.07.008 -
Journal of Clinical Oncology : Official... Jan 2024JCO The primary analysis of the Early positron emission tomography (ePET) Response-Adapted Treatment in localized Hodgkin Lymphoma H10 Trial demonstrated that in... (Randomized Controlled Trial)
Randomized Controlled Trial
JCO The primary analysis of the Early positron emission tomography (ePET) Response-Adapted Treatment in localized Hodgkin Lymphoma H10 Trial demonstrated that in ePET-negative patients, the risk of relapse increased when involved-node radiotherapy (INRT) was omitted and that in ePET-positive patients, switching from doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) to bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) significantly improved 5-year progression-free survival (PFS). Here, we report the final results of a preplanned analysis at a 10-year follow-up. In the favorable (F) ePET-negative group, the 10-year PFS rates were 98.8% versus 85.4% (hazard ratio [HR], 13.2; 95% CI, 3.1 to 55.8; value for noninferiority = .9735; difference test < .0001) in favor of ABVD + INRT; in the unfavorable (U) ePET-negative group, the 10-year PFS rates were 91.4% and 86.5% (HR, 1.52; 95% CI, 0.84 to 2.75; value for noninferiority = .8577; difference test = .1628). In ePET-positive patients, the difference in terms of PFS between standard ABVD and intensified BEACOPPesc was no longer statistically significant (HR, 0.67; 95% CI, 0.37 to 1.20; = .1777). In conclusion, the present long-term analysis confirms that in ePET-negative patients, the omission of INRT is associated with lower 10-year PFS. Instead, in ePET-positive patients, no significant difference between standard and experimental arms emerged although intensification with BEACOPPesc was safe, with no increase in late adverse events, namely, second malignancies.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Dacarbazine; Disease-Free Survival; Doxorubicin; Follow-Up Studies; Hodgkin Disease; Neoplasm Recurrence, Local; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 37967311
DOI: 10.1200/JCO.23.01745 -
Frontiers in Endocrinology 2023Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative... (Meta-Analysis)
Meta-Analysis
Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.
BACKGROUND
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
MATERIALS AND METHOD
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
RESULTS
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
CONCLUSION
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Topics: Humans; Male; Animals; Rats; Mice; Melatonin; Antioxidants; Iodine Radioisotopes; Semen; Thyroid Neoplasms; Oxidative Stress; Body Weight
PubMed: 37701901
DOI: 10.3389/fendo.2023.1184745 -
JAMA Oncology Apr 2023Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy....
IMPORTANCE
Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy and/or alkylating chemotherapy. Although radiation dose-response associations with breast, lung, stomach, pancreatic, and esophageal cancer after HL have been demonstrated, the association of radiation therapy with colorectal cancer remains unclear.
OBJECTIVE
To quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors.
DESIGN, SETTING, AND PARTICIPANTS
A nested case-control study examined 5-year HL survivors at 5 hospital centers in the Netherlands. Participants had been diagnosed with HL in 1964 to 2000, when they were 15 to 50 years of age, and were followed for a median of approximately 26 years. Survivors of HL who developed colorectal cancer and survivors who were selected as controls were individually matched on sex, age at HL diagnosis, and date of HL diagnosis. Data were analyzed from July 2021 to October 2022.
EXPOSURES
Mean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets.
MAIN OUTCOMES AND MEASURES
Excess rate ratios (ERRs) were modeled to evaluate the excess risk associated with each 1-gray increase in radiation dose, and potential effect modification by procarbazine was explored.
RESULTS
The study population included 316 participants (mean [SD] age at HL diagnosis, 33.0 [9.8] years; 221 [69.9%] men), 78 of whom were HL survivors who developed colorectal cancer (cases) and 238 who did not (controls). The median (IQR) interval between HL and colorectal cancer was 25.7 (18.2-31.6) years. Increased colorectal cancer rates were seen for patients who received subdiaphragmatic radiation therapy (rate ratio [RR], 2.4; 95% CI, 1.4-4.1) and those who received more than 8.4 g/m2 procarbazine (RR, 2.5; 95% CI, 1.3-5.0). Overall, colorectal cancer rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The association between radiation dose and colorectal cancer rate became stronger with increasing procarbazine dose: the ERR per gray to the whole bowel was 3.5% (95% CI, 0.4%-12.6%) for patients who did not receive procarbazine, and increased 1.2-fold (95% CI, 1.1-1.3) for each 1-g/m2 increase in procarbazine dose.
CONCLUSIONS AND RELEVANCE
This nested case-control study of 5-year HL survivors found a dose-response association between radiation therapy and colorectal cancer risk, and modification of this association by procarbazine. These findings may enable individualized colorectal cancer risk estimations, identification of high-risk survivors for subsequent screening, and optimization of treatment strategies.
Topics: Male; Humans; Child; Female; Hodgkin Disease; Procarbazine; Case-Control Studies; Survivors; Colorectal Neoplasms
PubMed: 36729438
DOI: 10.1001/jamaoncol.2022.7153 -
Klinicka Onkologie : Casopis Ceske a... 2017The optimal treatment for low-grade gliomas remains controversial. Neurosurgery, radiotherapy, and chemotherapy are the main treatment options. Despite advances in... (Review)
Review
BACKGROUND
The optimal treatment for low-grade gliomas remains controversial. Neurosurgery, radiotherapy, and chemotherapy are the main treatment options. Despite advances in oncology, there are still a lot of uncertainties, and the optimal sequences, combinations, and timings of these procedures have not yet been optimized. It is still unclear whether temozolomide can replace effective, but toxic PCV chemotherapy (procarbazine, lomustine, vincristine) and whether temozolomide can be used upfront alone instead of radiotherapy alone. Mature results from phase III trials (CODEL, EORTC 22033-26033) will provide answers to these questions. Correlative analyses of survival data and molecular marker findings (1p/19q codeletion, IDH1/2 mutation, and MGMT promoter methylation status) are essential. Due to slow progressive nature of the disease, all clinical trials with low-grade gliomas are complicated by the need for long-term follow-up to obtain valid mature data, which makes any new treatment procedures or developments in basic research developed during the course of closed clinical trials difficult to apply in daily clinical practice. An example is the recently published RTOG 9802 study evaluating the role of adjuvant PCV in combination with radiotherapy for the treatment of high-risk low-grade glioma patients where the recruitment of patients was initiated almost two decades ago. Health-related quality of life after treatment of patients with expected long-term survival is also very important and its maintenance is currently the focus of considerable interest.
AIM
The main objective of the present review is to summarize the results of key clinical trials and highlight controversial issues that could have an impact on future daily practice. Another aim is to discuss these issues in the light of newly established molecular markers from the new 2016 WHO Classification of Tumors of the Central Nervous System.Key words: glioma - astrocytoma - radiotherapy - temozolomide - PCV - cognition This work was supported by MH CZ - RVO (MMCI, 00209805) and by project of the Ministry of Education, Youths and Sports of the Czech Republic CEITEC 2020 (LQ1601). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 21. 2. 2017Accepted: 20. 3. 2017.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Chemotherapy, Adjuvant; Clinical Trials as Topic; Glioma; Humans; Radiotherapy, Adjuvant
PubMed: 29031035
DOI: 10.14735/amko2017337 -
Journal of Korean Medical Science Jun 2018While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the... (Clinical Trial)
Clinical Trial
BACKGROUND
While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O-methylguanine-DNA-methyltransferase (MGMT) promoter methylation.
METHODS
Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m) on day 1 and procarbazine (60 mg/m) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6).
RESULTS
One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities.
CONCLUSION
The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.
Topics: Adult; Aged; Antineoplastic Agents; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Dacarbazine; Disease-Free Survival; Female; Glioblastoma; Humans; Kaplan-Meier Estimate; Lomustine; Male; Middle Aged; Neoplasm Recurrence, Local; Procarbazine; Promoter Regions, Genetic; Temozolomide; Tumor Suppressor Proteins; Young Adult
PubMed: 29892208
DOI: 10.3346/jkms.2018.33.e167 -
Neurosurgical Focus Mar 2015The preferred management of suspected low-grade gliomas (LGGs) has been disputed, and the implications of molecular changes for medical and surgical management of LGGs... (Review)
Review
The preferred management of suspected low-grade gliomas (LGGs) has been disputed, and the implications of molecular changes for medical and surgical management of LGGs are important to consider. Current strategies that make use of molecular markers and imaging techniques and therapeutic considerations offer additional options for management of LGGs. Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes suggest a role for this abnormal metabolic pathway in the pathogenesis and progression of these primary brain tumors. Use of magnetic resonance spectroscopy can provide preoperative detection of IDH-mutated gliomas and affect surgical planning. In addition, IDH1 and IDH2 mutation status may have an effect on surgical resectability of gliomas. The IDH-mutated tumors exhibit better prognosis throughout every grade of glioma, and mutation may be an early genetic event, preceding lineage-specific secondary and tertiary alterations that transform LGGs into secondary glioblastomas. The O6-methylguanine-DNAmethyltransferase (MGMT) promoter methylation and 1p19q codeletion status can predict sensitivity to chemotherapy and radiation in low- and intermediate-grade gliomas. Thus, these recent advances, which have led to a better understanding of how molecular, genetic, and epigenetic alterations influence the pathogenicity of the different histological grades of gliomas, can lead to better prognostication and may lead to specific targeted surgical interventions and medical therapies.
Topics: Brain Neoplasms; DNA Modification Methylases; DNA Repair Enzymes; Decision Making; Epigenomics; Genetic Predisposition to Disease; Glioma; Humans; Isocitrate Dehydrogenase; Mutation; Neurosurgical Procedures; Tumor Suppressor Proteins
PubMed: 25727224
DOI: 10.3171/2015.1.FOCUS14745 -
Current Opinion in Oncology Nov 2015Genetic, epigenetic, and expression analyses have refined the traditional, histopathology-based classification of diffusely infiltrating gliomas. This review summarizes... (Review)
Review
PURPOSE OF REVIEW
Genetic, epigenetic, and expression analyses have refined the traditional, histopathology-based classification of diffusely infiltrating gliomas. This review summarizes these trends and implications for elderly patients.
RECENT FINDINGS
The vast majority of diffusely infiltrating gliomas in elderly patients share an unfavorable molecular phenotype, that is, telomerase reverse transcriptase promoter mutation in the absence of isocitrate dehydrogenase (IDH) mutation and 1p/19q codeletion. Histopathologically, these are mostly astrocytic tumors and treatment is guided by the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter. 1p/19q codeletion indicates oligodendroglial histology and benefit from the addition of procarbazine, chlorethyl-cyclohexyl-nitroso-urea/lomustine, and vincristine polychemotherapy to radiotherapy. These tumors are almost exclusively associated with IDH mutations, but their molecular profile is rare in elderly patients. Two large phase III trials, RTOG 0825 and AVAglio, failed to demonstrate an overall survival benefit from antiangiogenic therapy with bevacizumab added to combined chemoradiotherapy (TMZ) in patients with newly diagnosed glioblastoma, but a trend toward improved survival with increasing age can be noted. Ongoing clinical trials in elderly patients with diffusely infiltrating glioma will clarify the role of combined chemoradiotherapy, and of bevacizumab or other antiangiogenic agents as an adjunct to radiotherapy.
SUMMARY
The choice of first-line therapy in elderly patients with diffusely infiltrating glioma is between postoperative hypofractionated radiotherapy and chemotherapy, guided by MGMT methylation in most patients.
Topics: Aged; Angiogenesis Inhibitors; Antineoplastic Agents; Central Nervous System Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; DNA Methylation; DNA Modification Methylases; Epigenomics; Gene Expression Regulation, Neoplastic; Glioma; Humans; Isocitrate Dehydrogenase; Molecular Targeted Therapy; Telomerase
PubMed: 26397765
DOI: 10.1097/CCO.0000000000000236