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Expert Review of Neurotherapeutics Jun 2019: Glioblastoma multiforme (GBM) has a poor prognosis despite maximal surgical resection with subsequent multi-modal radiation and chemotherapy. Use of tobacco products... (Review)
Review
: Glioblastoma multiforme (GBM) has a poor prognosis despite maximal surgical resection with subsequent multi-modal radiation and chemotherapy. Use of tobacco products following diagnosis and during the period of treatment for non-neural tumors detrimentally affects treatment and prognosis. Approximately, 16-28% of patients with glioblastoma continue to smoke after diagnosis and during treatment. The literature is sparse for information-pertaining effects of smoking and nicotine on GBM treatment and prognosis. : This review discusses cellular pathways involved in GBM progression that might be affected by nicotine, as well as how nicotine may contribute to resistance to treatment. Similarities of GBM pathways to those in non-neural tumors are investigated for potential effects by nicotine. English language papers were identified using PubMed, Medline and Scopus databases using a combination of keywords including but not limited to the following: nicotine, vaping, tobacco, e-cigarettes, smoking, vaping AND glioblastoma or brain cancer OR/AND temozolomide, carmustine, methotrexate, procarbazine, lomustine, vincristine, and neural tumor cell lines. : Understanding the impact of nicotine on treatment and resistance to chemotherapeutics should allow physicians to educate their patients with GBM with evidence-based recommendations about the effects of continuing to use nicotine-containing products after diagnosis and during treatment.
Topics: Brain Neoplasms; Chemoradiotherapy; Glioblastoma; Humans; Nicotine; Outcome Assessment, Health Care; Smoking
PubMed: 31092064
DOI: 10.1080/14737175.2019.1617701 -
CNS Oncology 2015Anaplastic oligodendrogliomas (AOs) are rare brain tumors responsive to chemotherapy with procarbazine, lomustine (CCNU) and vincristine (PCV), especially when harboring... (Review)
Review
Anaplastic oligodendrogliomas (AOs) are rare brain tumors responsive to chemotherapy with procarbazine, lomustine (CCNU) and vincristine (PCV), especially when harboring 1p19q codeletion. However, with the emergence of temozolomide as an easier to administer and less toxic alternative regimen, PCV fell out of favor. Now, long-term results of two Phase III studies conceived in the 1990s, Radiation Therapy Oncology Group (RTOG) 9402 and European Organisation for Research and Treatment of Cancer (EORTC) 26951, resurrected debate about the potential role of PCV. No adequately powered prospective trial has compared chemotherapy alone with PCV versus temozolomide for newly diagnosed 1p19q codeleted AOs. Available data suggest responses may be both more frequent and more durable with PCV, and survival may be longer. Which regimen is 'better', therefore, depends on the importance of different metrics (i.e., toxicity, complexity, efficacy), and await definitive results from the important ongoing and recently redesigned CODEL international Phase III trial.
Topics: Antineoplastic Agents; Brain Neoplasms; Clinical Trials as Topic; Dacarbazine; Humans; Lomustine; Oligodendroglioma; Procarbazine; Temozolomide; Treatment Outcome; Vincristine
PubMed: 26544062
DOI: 10.2217/cns.15.36 -
Turkish Journal of Haematology :... May 2019
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Drug Eruptions; Etoposide; Female; Hodgkin Disease; Humans; Prednisone; Procarbazine; Vincristine
PubMed: 30600679
DOI: 10.4274/tjh.galenos.2019.2018.0317 -
Seminars in Hematology Jul 2016There is now good evidence that the escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) is more... (Review)
Review
There is now good evidence that the escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone) is more effective in controlling advanced-stage Hodgkin lymphoma (HL) than the widely used ABVD regimen (adriamycin, bleomycin, vinblastine, dacarbazine), but the extra efficacy comes at the expense of both short- and long-term toxicity, and there is debate as to whether overall survival is affected. Baseline prognostic factors have proven of limited utility for determining which patients require more intensive therapy and recent studies have sought to use interim fluoro-deoxyglucose positron emission tomography (FDG-PET) evaluation as a means to guide the modulation of treatment, both upwards and downwards in intensity. These suggest that if treatment starts with ABVD then patients remaining PET-positive after 2 months can be salvaged with escalated BEACOPP in around 65% of cases, but those becoming PET-negative may still experience recurrences in 15%-20%, an event that is more common in those with more advanced disease at presentation. There are early data to suggest that starting with escalated BEACOPP may reduce the rate of recurrence after a negative interim PET to less than 10%. This may be an attractive approach for those with very high-risk features at presentation, but risks overtreating many patients if applied nonselectively. New regimens incorporating antibody-drug conjugates may shift the balance of efficacy and toxicity once again, and further studies are underway to evaluate this.
Topics: Antineoplastic Combined Chemotherapy Protocols; Hodgkin Disease; Humans; Neoplasm Staging; Salvage Therapy; Treatment Outcome
PubMed: 27496308
DOI: 10.1053/j.seminhematol.2016.05.006 -
Cancer Radiotherapie : Journal de La... Oct 2014Gliomas are the most frequent primary brain tumors. Their care is difficult because of the proximity of organs at risk. The treatment of glioblastoma includes surgery... (Review)
Review
Gliomas are the most frequent primary brain tumors. Their care is difficult because of the proximity of organs at risk. The treatment of glioblastoma includes surgery followed by chemoradiation with the protocol of Stupp et al. The addition of bevacizumab allows an increase in progression-free survival by 4 months but it does not improve overall survival. This treatment is reserved for clinical trials. Intensity modulation radiotherapy may be useful to reduce the neurocognitive late effects in different types of gliomas. In elderly patients an accelerated radiotherapy 40 Gy in 15 fractions allows a similar survival to standard radiotherapy. O(6)-methylguanine-DNA methyltransferase (MGMT) status may help to choose between chemotherapy and radiotherapy. There is no standard for the treatment of recurrent gliomas. Re-irradiation in stereotactic conditions allows a median survival of 8 to 12.4 months. Anaplastic gliomas with 1p19q mutation have a greater sensibility to chemotherapy by procarbazine, lomustine and vincristine. Chemoradiotherapy in these patients has become the standard treatment. Many studies are underway testing targeted therapies, their place in the therapeutic management and new radiotherapy techniques.
Topics: Age Factors; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Brain Neoplasms; Chemoradiotherapy; Chromosome Deletion; Chromosomes, Human, Pair 1; Clinical Trials as Topic; Combined Modality Therapy; Dacarbazine; Dose Fractionation, Radiation; Drug Resistance, Neoplasm; Glioma; Humans; Lomustine; Methylation; Multicenter Studies as Topic; Neoplasm Proteins; Neurosurgical Procedures; O(6)-Methylguanine-DNA Methyltransferase; Procarbazine; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Temozolomide; Treatment Outcome; Vincristine
PubMed: 25201633
DOI: 10.1016/j.canrad.2014.07.147 -
Expert Review of Neurotherapeutics Jun 2015Anaplastic glioma (AG) is divided into three morphology-based groups (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma) as well as three... (Review)
Review
Anaplastic glioma (AG) is divided into three morphology-based groups (anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma) as well as three molecular groups (glioma-CpG island methylation phenotype [G-CIMP] negative, G-CIMP positive non-1p19q codeleted tumors and G-CIMP positive codeleted tumors). The RTOG 9402 and EORTC 26951 trials established radiotherapy plus (procarbazine, lomustine, vincristine) chemotherapy as the standard of care in 1p/19q codeleted AG. Uni- or non-codeleted AG are currently best treated with radiotherapy only or alkylator-based chemotherapy only as determined by the NOA-04 trial. Maturation of NOA-04 and results of the currently accruing studies, CODEL (for codeleted AG) and CATNON (for uni or non-codeleted AG), will likely refine current up-front treatment recommendations for AG.
Topics: Brain Neoplasms; Disease Management; Glioma; Humans; Isocitrate Dehydrogenase; Mutation
PubMed: 25936680
DOI: 10.1586/14737175.2015.1042455 -
Current Opinion in Neurology Dec 2020The management of low-grade (grade II) oligodendrogliomas is still controversial, due to their rarity and long-term survival. According to recent WHO 2016 Classification... (Review)
Review
PURPOSE OF REVIEW
The management of low-grade (grade II) oligodendrogliomas is still controversial, due to their rarity and long-term survival. According to recent WHO 2016 Classification of central nervous system tumors oligodendrogliomas are defined by the coexistence of molecular alterations, such as isocitrate dehydrogenase (IDH)1/2 mutations and 1p/19q codeletion. These tumors have better outcome and higher response to chemotherapy compared with diffuse astrocytomas.
RECENT FINDINGS
The association of radiotherapy and procarbazine, lomustine (CCNU), vincristine chemotherapy in low-grade oligodendrogliomas is definitely superior over radiotherapy alone, and yields median progression-free survival and overall survival values exceeding by far 10 years. Chemotherapy alone yields results that are inferior compared with radiotherapy + procarbazine, CCNU, vincristine but may better preserve cognitive functions from radiotherapy-induced damage. Chemosensitivity of oligodendrogliomas is related to a high percentage of O6-methylguanine-DNA methyltransferase methylation and low expression of DNA repair genes. Recurrent defects in mismatch repair pathways may induce hypermutation and secondary resistance to temozolomide, but not to nitrosoureas.
SUMMARY
Reoperation at progression following initial chemotherapy is increasingly adopted, thus allowing a further delay of radiotherapy. In the future targeting IDH1/2 mutations following incomplete surgery may represent a new innovative option.
Topics: Antineoplastic Agents; Brain Neoplasms; Humans; Lomustine; Oligodendroglioma; Temozolomide; Treatment Outcome; Vincristine
PubMed: 33027142
DOI: 10.1097/WCO.0000000000000866 -
BMC Cancer Aug 2023Older primary central nervous system lymphoma (PCNSL) patients have an inferior prognosis compared to younger patients because available evidence on best treatment is... (Randomized Controlled Trial)
Randomized Controlled Trial
Age-adjusted high-dose chemotherapy followed by autologous stem cell transplantation or conventional chemotherapy with R-MP as first-line treatment in elderly primary CNS lymphoma patients - the randomized phase III PRIMA-CNS trial.
BACKGROUND
Older primary central nervous system lymphoma (PCNSL) patients have an inferior prognosis compared to younger patients because available evidence on best treatment is scarce and treatment delivery is challenging due to comorbidities and reduced performance status. High-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) after high-dose methotrexate (MTX)-based immuno-chemotherapy has become an increasingly used treatment approach in eligible elderly PCNSL patients with promising feasibility and efficacy, but has not been compared with conventional chemotherapy approaches. In addition, eligibility for HCT-ASCT in elderly PCNSL is not well defined. Geriatric assessment (GA) may be helpful in selecting patients for the best individual treatment choice, but no standardized GA exists to date. A randomized controlled trial, incorporating a GA and comparing age-adapted HCT-ASCT treatment with conventional chemotherapy is needed.
METHODS
This open-label, multicenter, randomized phase III trial with two parallel arms will recruit 310 patients with newly diagnosed PCNSL > 65 years of age in 40 centers in Germany and Austria. The primary objective is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with rituximab, MTX, procarbazine (R-MP) followed by maintenance with procarbazine in terms of progression free survival (PFS). Secondary endpoints include overall survival (OS), event free survival (EFS), (neuro-)toxicity and quality of life (QoL). GA will be conducted at specific time points during the course of the study. All patients will be treated with a pre-phase rituximab-MTX (R-MTX) cycle followed by re-assessment of transplant eligibility. Patients judged transplant eligible will be randomized (1:1). Patients in arm A will be treated with 3 cycles of R-MP followed by maintenance therapy with procarbazine for 6 months. Patients in arm B will be treated with 2 cycles of MARTA (R-MTX/AraC) followed by busulfan- and thiotepa-based HCT-ASCT.
DISCUSSION
The best treatment strategy for elderly PCNSL patients remains unknown. Treatments range from palliative to curative but more toxic therapies, and there is no standardized measure to select patients for the right treatment. This randomized controlled trial will create evidence for the best treatment strategy with the focus on developing a standardized GA to help define eligibility for an intensive treatment approach.
TRIAL REGISTRATION
German clinical trials registry DRKS00024085 registered March 29, 2023.
Topics: Aged; Humans; Quality of Life; Hematopoietic Stem Cell Transplantation; Procarbazine; Rituximab; Transplantation, Autologous; Lymphoma
PubMed: 37596517
DOI: 10.1186/s12885-023-11193-7 -
Current Treatment Options in Oncology Oct 2016The revised World Health Organization (WHO) classification of tumors of the central nervous system of 2016 combines biology-driven molecular marker diagnostics with... (Review)
Review
The revised World Health Organization (WHO) classification of tumors of the central nervous system of 2016 combines biology-driven molecular marker diagnostics with classical histological cancer diagnosis. Reclassification of gliomas by molecular similarity beyond histological boundaries improves outcome prediction and will increasingly guide treatment decisions. This change in paradigms implies more personalized and eventually more efficient therapeutic approaches, but the era of molecular targeted therapies for gliomas is yet at its onset. Promising results of molecularly targeted therapies in genetically less complex gliomas with circumscribed growth such as subependymal giant cell astrocytoma or pilocytic astrocytoma support further development of molecularly targeted therapies. In diffuse gliomas, several molecular markers that predict benefit from alkylating agent chemotherapy have been identified in recent years. For example, co-deletion of chromosome arms 1p and 19q predicts benefit from polychemotherapy with procarbazine, CCNU (lomustine), and vincristine (PCV) in patients with anaplastic oligodendroglioma, and the presence of 1p/19q co-deletion was integrated as a defining feature of oligodendroglial tumors in the revised WHO classification. However, the tremendous increase in knowledge of molecular drivers of diffuse gliomas on genomic, epigenetic, and gene expression levels has not yet translated into effective molecular targeted therapies. Multiple reasons account for the failure of early clinical trials of molecularly targeted therapies in diffuse gliomas, including the lack of molecular entry controls as well as pharmacokinetic and pharmacodynamics issues, but the key challenge of specifically targeting the molecular backbone of diffuse gliomas is probably extensive clonal heterogeneity. A more profound understanding of clonal selection, alternative activation of oncogenic signaling pathways, and genomic instability is warranted to identify effective combination treatments and ultimately improve survival.
Topics: Biomarkers, Tumor; Brain Neoplasms; Cell Transformation, Neoplastic; Chromosome Aberrations; DNA Methylation; Disease Management; Glioma; Histones; Humans; Molecular Diagnostic Techniques; Molecular Targeted Therapy; Mutation; Neoplasm Grading; Neoplasm Staging; Promoter Regions, Genetic; Treatment Outcome
PubMed: 27501915
DOI: 10.1007/s11864-016-0430-4 -
Blood Apr 2018With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients.... (Review)
Review
With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPP) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPP improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti-programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Disease-Free Survival; Doxorubicin; Etoposide; Female; Hodgkin Disease; Humans; Male; Neoplasm Staging; Positron-Emission Tomography; Prednisone; Procarbazine; Risk Assessment; Sex Factors; Survival Rate; Vinblastine; Vincristine
PubMed: 29500174
DOI: 10.1182/blood-2017-10-772665