-
Annals of the American Thoracic Society Jan 2024The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic... (Meta-Analysis)
Meta-Analysis
The American Thoracic Society convened an international, multidisciplinary panel to develop clinical practice guidelines for the treatment of systemic sclerosis-associated interstitial lung disease (SSc-ILD). To conduct a systematic review and evaluate the literature to determine whether patients with SSc-ILD should be treated with cyclophosphamide. A literature search was conducted across the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases through June 2022 for studies using cyclophosphamide to treat patients with SSc-ILD. Mortality, disease progression, quality of life, and adverse event data were extracted, and meta-analyses were performed when possible. The Grading of Recommendations, Assessment, Development and Evaluation Working Group method was used to assess the quality of evidence. Five studies were included; two randomized controlled trials compared cyclophosphamide versus placebo, and one randomized controlled trial and two retrospective case-control studies compared cyclophosphamide versus mycophenolate. Compared with placebo, there was a 2.83% reduction in the decline at 12 months for forced vital capacity (FVC) % predicted using cyclophosphamide (95% confidence interval [CI], 0.80-4.87; low evidence). There were improvements in breathlessness (Transition Dyspnea Index mean difference [MD], 2.90; 95% CI, 1.94-3.86; minimum clinically important difference, 1; moderate evidence) and disability (Health Assessment Questionnaire-Disability Index MD, -0.16; 95% CI, -0.28 to -0.04; minimum clinically important difference, -0.14; moderate evidence). There were increased risks of leukopenia and constitutional symptoms using cyclophosphamide, but no difference in mortality. When cyclophosphamide was compared with mycophenolate, there were differences in diffusing capacity of the lung for carbon monoxide % predicted favoring mycophenolate at 6 months (MD, -3.67%; 95% CI, -6.3% to -1.1% unadjusted; MD, -4.88%; 95% CI, -7.3% to -2.5% adjusted for alveolar volume; moderate evidence), 12 months (MD, -5.90%; 95% CI, -8.4% to -3.4% adjusted for alveolar volume; moderate evidence), and 18 months (MD, -3.26%; 95% CI, -6.1% to -0.4%; moderate evidence), but not at 24 months. There were no differences in FVC % predicted, mortality, or quality-of-life outcomes, but participants were more likely to prematurely discontinue cyclophosphamide compared with mycophenolate (relative risk, 1.70; 95% CI, 1.10-2.63; high-certainty evidence). A review of the published evidence shows that cyclophosphamide is effective in SSc-ILD compared with placebo, with an increased risk of side effects. However, mycophenolate may be equivocal or better than cyclophosphamide. Clinicians and patients should weigh the potential benefits and risks with respect to individual patient circumstances and preferences.
Topics: Humans; Retrospective Studies; Quality of Life; Cyclophosphamide; Immunosuppressive Agents; Lung Diseases, Interstitial; Dyspnea; Scleroderma, Systemic
PubMed: 37772975
DOI: 10.1513/AnnalsATS.202301-053OC -
Critical Reviews in Oncology/hematology Apr 2021Diffuse large B cell Lymphoma (DLBCL) is a potentially curative lymphoma with increasing incidence with ageing. Treatment of elderly DLBCL patients represents a... (Review)
Review
INTRODUCTION
Diffuse large B cell Lymphoma (DLBCL) is a potentially curative lymphoma with increasing incidence with ageing. Treatment of elderly DLBCL patients represents a particular challenge due to their comorbidities and performance status.
METHODS
A search for original articles focused on the treatment of elderly DLBCL patients was performed in PubMed database and 633 were found and reviewed. Thirty-eight studies meeting our inclusion criteria were published since 2007.
RESULTS
Thirteen studies were retrospective and 25 phase II/III clinical trials. Most of them investigated the efficacy of dose-adjusted R-CHOP regimen. Alternative therapeutic drugs together with geriatric assessment were also evaluated. For fit patients aged 80 and over, the strongest evidence favours R-miniCHOP regimen.
CONCLUSION
A dose-adjusted R-CHOP may be the recommended treatment in elderly DLBCL patients. New tools such as the Comprehensive Geriatric Assessment provide useful guidance for treatment choice, based on comorbidities and frailty index of this group.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Comorbidity; Cyclophosphamide; Doxorubicin; Geriatric Assessment; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone; Retrospective Studies; Rituximab; Treatment Outcome; Vincristine
PubMed: 33675907
DOI: 10.1016/j.critrevonc.2021.103294 -
Critical Reviews in Oncology/hematology Nov 2021CNS prophylaxis is commonly used in Diffuse Large B-Cell Lymphoma (DLBCL) patients with risk features for CNS relapse. This systematic review and meta-analysis compares... (Meta-Analysis)
Meta-Analysis Review
CNS prophylaxis is commonly used in Diffuse Large B-Cell Lymphoma (DLBCL) patients with risk features for CNS relapse. This systematic review and meta-analysis compares CNS relapse rates with and without CNS prophylaxis, for patients at intermediate to high CNS relapse risk. Studies reporting CNS relapse risk category and CNS outcomes with and without CNS prophylaxis for antiCD20-CHOP treated DLBCL patients were included. 10 studies with 3770 patients at intermediate to high CNS relapse risk were analyzed. No significant difference in the pooled Absolute Risk Difference (ARD 0.01, 95 % CI -0.01 to 0.02, P = 0.61) or Risk (RR 1.22, 95 % CI 0.81-1.83, P = 0.34) was noted in patients with and without CNS prophylaxis. There were also no differences within pre-specified subgroups of IV Methotrexate or IT chemotherapy. However, the quality of evidence supporting these observations was low. A meta-analysis of individual patient data will help evaluate the benefit of CNS prophylaxis strategies.
Topics: Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Central Nervous System Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Prednisone; Rituximab; Vincristine
PubMed: 34656744
DOI: 10.1016/j.critrevonc.2021.103507 -
Clinical and Investigative Medicine.... Jun 2020We used the Cochrane systematic review to analyze the effectiveness and safety of rituximab for lupus nephritis.
PURPOSE
We used the Cochrane systematic review to analyze the effectiveness and safety of rituximab for lupus nephritis.
METHODS
Systematic search was performed among Cochrane clinical controlled trials database, MEDLINE, MEDLINE-IN-Process and Other Non-Indexed Citations, EMBASE, EBSCO CINAHL, CNKI, VIP and Wanfang database from the establishment of the database to February 2016. The effectiveness and safety were evaluated in terms of the complete remission rate, total remission rate, urinary protein, Systemic Lupus Erythematosus Disease Activity Index changes and adverse events rate. Data were analyzed by the Review Manager Software version 5.3.
RESULTS
Five RCTs that met the inclusion criteria, including a total of 238 patients, were enrolled in our study. The results showed that the complete remission rate in rituximab group was a significantly higher than that of cyclophosphamide group. The difference between the two groups was statistically significant (OR=2.80, 95%CI(1.08,7.26), P=0.03). But there was no significant difference between the two groups in partial and total remission rate. The complete remission rate, partial remission rate and total remission rate in rituximab treatment group was similar compared with mycophenolate mofetil group and rituximab combined with cyclophosphamide group. The adverse reaction rate was also similar among the groups.
CONCLUSION
The study systematically analyzed the effectiveness and safety of rituximab for lupus nephritis, which suggested that the complete remission rate of rituximab in the treatment of lupus nephritis was a significantly higher than that of cyclophosphamide group, while the effectiveness and safety was of no difference compared with cyclophosphamide and mycophenolate mofetil.
Topics: Cyclophosphamide; Humans; Immunosuppressive Agents; Lupus Nephritis; Mycophenolic Acid; Rituximab; Treatment Outcome
PubMed: 32593276
DOI: 10.25011/cim.v43i2.33864 -
Scientific Reports Jan 2024We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for... (Meta-Analysis)
Meta-Analysis
We aimed to summarize the cancer risk among patients with indication of group I pharmaceuticals as stated in monographs presented by the International Agency for Research on Cancer working groups. Following the PRISMA guidelines, a comprehensive literature search was conducted using the PubMed database. Pharmaceuticals with few studies on cancer risk were identified in systematic reviews; those with two or more studies were subjected to meta-analysis. For the meta-analysis, a random-effects model was used to calculate the summary relative risks (SRRs) and 95% confidence intervals (95% CIs). Heterogeneity across studies was presented using the Higgins I square value from Cochran's Q test. Among the 12 group I pharmaceuticals selected, three involved a single study [etoposide, thiotepa, and mustargen + oncovin + procarbazine + prednisone (MOPP)], seven had two or more studies [busulfan, cyclosporine, azathioprine, cyclophosphamide, methoxsalen + ultraviolet (UV) radiation therapy, melphalan, and chlorambucil], and two did not have any studies [etoposide + bleomycin + cisplatin and treosulfan]. Cyclosporine and azathioprine reported increased skin cancer risk (SRR = 1.32, 95% CI 1.07-1.62; SRR = 1.56, 95% CI 1.25-1.93) compared to non-use. Cyclophosphamide increased bladder and hematologic cancer risk (SRR = 2.87, 95% CI 1.32-6.23; SRR = 2.43, 95% CI 1.65-3.58). Busulfan increased hematologic cancer risk (SRR = 6.71, 95% CI 2.49-18.08); melphalan was associated with hematologic cancer (SRR = 4.43, 95% CI 1.30-15.15). In the systematic review, methoxsalen + UV and MOPP were associated with an increased risk of skin and lung cancer, respectively. Our results can enhance persistent surveillance of group I pharmaceutical use, establish novel clinical strategies for patients with indications, and provide evidence for re-categorizing current group I pharmaceuticals into other groups.
Topics: Humans; Etoposide; Methoxsalen; Azathioprine; Melphalan; Busulfan; Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Cyclosporins; Pharmaceutical Preparations
PubMed: 38172159
DOI: 10.1038/s41598-023-50602-6 -
Rheumatology (Oxford, England) Mar 2022SS with childhood onset is a rare autoimmune disease characterized by heterogeneous presentation. The lack of validated classification criteria makes it challenging to...
OBJECTIVES
SS with childhood onset is a rare autoimmune disease characterized by heterogeneous presentation. The lack of validated classification criteria makes it challenging to diagnose. Evidence-based guidelines for treatment of juvenile SS are not available due to the rarity of disease and the paucity of research in this patient population. This systematic review aims to summarize and appraise the current literature focused on pharmacological strategies for management of SS with childhood onset.
METHODS
PubMed and MEDLINE/Scopus databases up to December 2020 were screened for suitable reports highlighting pharmacological treatment of SS with childhood onset using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 reporting checklist. Animal studies were excluded.
RESULTS
A total of 43 studies (34 case reports, 8 mini case series and 1 pilot study) were eligible for analysis. The studies retrieved included girls in 88% (120/137) of cases and had very low confidence levels. HCQ was prescribed for parotid swelling, as well as in association with MTX and NSAIDs in patients with arthritis and arthralgia. Corticosteroids such as long courses of oral prednisone and i.v. methylprednisolone were commonly prescribed for children with severe disease presentations. Rituximab was mainly indicated for mucosa-associated lymphoid tissue lymphoma and renal and nervous system complications. Other conventional DMARDs were prescribed in selected cases with extraglandular manifestations.
CONCLUSION
Various therapies are used for the management of juvenile SS and are prescribed based on expert clinician's opinion. There are currently no good-quality studies that allow clinical recommendations for treatment of SS with childhood onset.
Topics: Antirheumatic Agents; Azathioprine; Cyclophosphamide; Cyclosporine; Glucocorticoids; Humans; Hydroxychloroquine; Methotrexate; Rituximab; Sjogren's Syndrome
PubMed: 34289032
DOI: 10.1093/rheumatology/keab579 -
Expert Review of Clinical Immunology Mar 2020: To systematically review risk of sustained amenorrhea with intravenous (IV) cyclophosphamide in autoimmune rheumatic disease (ARD), and evaluate efficacy of... (Meta-Analysis)
Meta-Analysis
A systematic review and meta-analysis of the gonadotoxic effects of cyclophosphamide and benefits of gonadotropin releasing hormone agonists (GnRHa) in women of child-bearing age with autoimmune rheumatic disease.
: To systematically review risk of sustained amenorrhea with intravenous (IV) cyclophosphamide in autoimmune rheumatic disease (ARD), and evaluate efficacy of gonadotropin-releasing hormone agonists (GnRHa) to reduce this risk.: Systematic search for papers reporting incidence of sustained amenorrhea ≥12 months in ARD following: IV cyclophosphamide; or GnRHa and IV cyclophosphamide compared to IV cyclophosphamide alone.: From 31 articles and 1388 patients (mean age 27.7 years) sustained amenorrhea occurred in 273 patients (19.7%). Of 56 patients (mean age range 23.9-25.6 years) receiving GnRHa and IV cyclophosphamide, and 37 controls (mean age range 25-30.1 years) given IV cyclophosphamide only, sustained amenorrhea occurred in 2/56 (3.6%) patients treated with GnRHa, compared to 15/37 (40.5%) controls. Pooled odds ratio of sustained amenorrhea with GnRHa and cyclophosphamide versus cyclophosphamide alone was 0.054 (95% CI 0.0115-0.2576 p < 0.001), corresponding to a number needed to treat of 2.7 (95% CI 1.955-4.388) and absolute risk reduction of 36.95% (95% CI 35.6-38.4%).: Sustained amenorrhea with IV cyclophosphamide was observed in patients with ARD, especially with increasing age and cumulative doses >5 g. GnRHa reduced this risk and should be considered with IV cyclophosphamide in women of childbearing age with ARD.
Topics: Administration, Intravenous; Adult; Amenorrhea; Autoimmune Diseases; Cyclophosphamide; Drug-Related Side Effects and Adverse Reactions; Female; Gonadotropin-Releasing Hormone; Humans; Rheumatic Diseases; Risk
PubMed: 32005081
DOI: 10.1080/1744666X.2020.1724091 -
Annals of Hematology Mar 2022This study aims to evaluate the efficacy, safety, and long-term cost-effectiveness of fixed-dose busulfan (Bu) administration and pharmacokinetically (PK) guided... (Meta-Analysis)
Meta-Analysis
Fixed-dose administration and pharmacokinetically guided adjustment of busulfan dose for patients undergoing hematopoietic stem cell transplantation: a meta-analysis and cost-effectiveness analysis.
This study aims to evaluate the efficacy, safety, and long-term cost-effectiveness of fixed-dose busulfan (Bu) administration and pharmacokinetically (PK) guided adjustment of Bu dose for patients who underwent hematopoietic stem cell transplantation. The efficacy and safety of both dosing strategies were compared using a systematic review and meta-analysis. A Markov model was used in estimating relevant cost and health outcomes from the perspective of the health system. The primary outcomes of interest were lifetime cost, quality adjusted life-years (QALYs) gained, and incremental cost-effectiveness ratio (ICER) in dollar per QALY gained. Results showed that progression-free survival and overall survival in the PK-guided group were higher than that in the fixed-dose group, and the PK-guided group was associated with low non-relapse mortality and relapse rate. In contrast to safety, the incidence of acute graft-versus-host disease (GVHD) was the same in the two groups (P > 0.05). Cost-effectiveness analysis showed that the QALY of the PK-guided group (12.8135 QALYs and $582,475.07) increased by 2.0609 relative to that in the fixed-dose group (10.7526 QALYs and $562,833.20), and the ICER was $9530.72/QALY. One-way and probability sensitivity analyses confirmed the reliability of the results. In conclusion, the PK-guided approach has higher efficacy and is safer.
Topics: Busulfan; Cost-Benefit Analysis; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Quality-Adjusted Life Years
PubMed: 35091794
DOI: 10.1007/s00277-021-04733-3 -
Critical Reviews in Oncology/hematology Jul 2021Doxorubicin represents the mainstay in the upfront treatment of diffuse large B-cell lymphoma (DLBCL) patients. However, its administration is sometimes hampered by the... (Meta-Analysis)
Meta-Analysis Review
Doxorubicin represents the mainstay in the upfront treatment of diffuse large B-cell lymphoma (DLBCL) patients. However, its administration is sometimes hampered by the coexistence of former comorbidities/cardiac issues, especially in the elderly population. Liposome encapsulated drug delivery systems have been adopted to reduce the exposure of normal tissues to the drug, both in solid cancers and lymphomas. Despite claims for lower toxicity, the efficacy of non-pegylated liposome doxorubicin (NPLD) in DLBCL, as compared to standard doxorubicin, has never been established. We systematically reviewed relevant literature of NPLD in lymphoma treatment. Adjusting for age/comorbidities, our metanalysis revealed that the use of combinations including NPLD (R-COMP) were non-inferior in terms of response, overall and progression-free survival to the standard of care (R-CHOP) in overlapping series of DLBCL patients. R-COMP may represent a safe and active option for elderly patients with DLBCL, or for those with some extent of cardiac impairment at baseline.
Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Prednisone; Rituximab; Treatment Outcome; Vincristine
PubMed: 34087342
DOI: 10.1016/j.critrevonc.2021.103377 -
Journal of Neuro-oncology Mar 2024Leptomeningeal disease (LMD) secondary to high grade glioma (HGG), such as glioblastoma (GBM), are characterized by the spread of tumor cells to the leptomeninges which... (Review)
Review
BACKGROUND
Leptomeningeal disease (LMD) secondary to high grade glioma (HGG), such as glioblastoma (GBM), are characterized by the spread of tumor cells to the leptomeninges which further complicates treatment approaches. Intrathecal (IT) chemotherapy has surfaced as a potential strategy to bypass the blood-brain barrier and address the challenges posed by disseminated disease. Here, we present a review of the safety and efficacy of IT chemotherapy in the treatment of LMD secondary to HGG.
METHODS
A systematic review following PRISMA guidelines was conducted searching PubMed and Embase from January 1995 to September 2022 using specified terms related to IT chemotherapy for LMD. Included articles involved patients diagnosed with LMD from HGG, treated with intrathecal chemotherapy, and provided survival data. Data, including demographics, tumor characteristics, treatment, and survival information, were collected and independently extracted.
RESULTS
A total of 68 patients across 10 clinical studies were diagnosed with LMD from HGG and included in the review. Among these patients, the average age at diagnosis was 44.2 years. GBM was the most common tumor type (n = 58, 85.3%). A majority of the patients presented with recurrent disease (n = 29, 60.4%). The review encompassed various IT chemotherapy regimens, including mafosfamide, thio-TEPA, 5-fluoro-2'-deoxyuridine (FdUrd), methotrexate (MTX), and cytarabine; however, dosages and frequencies were inconsistently reported. The mean progression-free survival (PFS) and overall survival (OS) for this cohort were 7.5 months and 11.7 months, respectively. Common side effects of IT chemotherapy included headaches, nausea, and vomiting, with more severe complications such as myelotoxicity, disseminated intravascular coagulopathy, meningitis, and gastrointestinal toxicity reported in some cases.
CONCLUSION
LMD continues to be an uncommon complication associated with HGG with a poor prognosis. This article provides an overview of the presently available literature on IT chemotherapy for LMD secondary to HGG, and their respective treatment protocols with overall survival attributes. Additional research is warranted to ascertain how to maximize the potential efficacy of IT chemotherapy as a treatment option.
Topics: Humans; Adult; Brain Neoplasms; Glioma; Glioblastoma; Thiotepa; Meninges
PubMed: 38294637
DOI: 10.1007/s11060-024-04582-w