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The Cochrane Database of Systematic... May 2010The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of anthracyclines is limited by the occurrence of cardiotoxicity. In an effort to prevent this cardiotoxicity, different anthracycline derivates have been studied.
OBJECTIVES
To determine the occurrence of cardiotoxicity with the use of different anthracycline derivates in cancer patients.
SEARCH STRATEGY
We searched The Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 to 29 May 2009) and EMBASE (1980 to 2 June 2009). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing-trials-databases.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in which different anthracycline derivates were compared in cancer patients (children and adults).
DATA COLLECTION AND ANALYSIS
Two authors independently performed study selection, assessment of risk of bias and data-extraction including adverse effects.
MAIN RESULTS
We identified five RCTs of varying quality addressing epirubicin versus doxorubicin (1036 patients) with the same dose. The meta-analysis showed no evidence for a significant difference in the occurrence of clinical heart failure between the treatment groups (RR = 0.36, 95% CI 0.12 to 1.11). However, there is some suggestion of a lower rate of clinical heart failure in patients treated with epirubicin.We identified two RCTs with varying quality addressing liposomal-encapsulated doxorubicin versus conventional doxorubicin (521 patients). The meta-analysis showed a significantly lower rate of both clinical heart failure and clinical and subclinical heart failure combined in patients treated with liposomal-encapsulated doxorubicin (RR = 0.20, 95% CI 0.05 to 0.75 and RR = 0.38, 95% CI 0.24 to 0.59 respectively). It should be noted that in one of the studies patients in the liposomal-encapsulated doxorubicin group received a higher cumulative anthracycline dose than patients in the doxorubicin group.For the other possible combinations of different anthracycline derivates only one RCT (epirubicin versus liposomal-encapsulated doxorubicin) or no RCT was identified.
AUTHORS' CONCLUSIONS
We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.
Topics: Adult; Antibiotics, Antineoplastic; Cardiac Output, Low; Child; Doxorubicin; Epirubicin; Heart; Humans; Liposomes; Neoplasms; Randomized Controlled Trials as Topic
PubMed: 20464735
DOI: 10.1002/14651858.CD005006.pub4 -
Musculoskeletal Surgery Mar 2023Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered... (Review)
Review
Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered in cases of disease progression. This systematic review aimed to evaluate the effectiveness and toxicity of each medical treatment by reviewing only the studies that included progressive disease as the inclusion criterion. We searched the EMBASE, PubMed, and CENTRAL databases to identify published studies for progressive DTs. The disease control rates of the medical treatments, such as low-dose chemotherapy with methotrexate plus vinblastine or vinorelbine, imatinib, sorafenib, pazopanib, nilotinib, anlotinib, doxorubicin-based agents, liposomal doxorubicin, hydroxyurea, and oral vinorelbine for progressive DTs were 71-100%, 78-92%, 67-96%, 84%, 88%, 86%, 89-100%, 90-100%, 75%, and 64%, respectively. Low-dose chemotherapy, sorafenib, pazopanib, nilotinib, anlotinib, and liposomal doxorubicin had similar toxicities. Sorafenib and pazopanib were less toxic than imatinib. Doxorubicin-based chemotherapy was associated with the highest toxicity. Hydroxyurea and oral vinorelbine exhibited the lowest toxicity. Stepwise therapy escalation from an initial, less toxic treatment to more toxic agents is recommended for progressive DTs. Sorafenib and pazopanib had limited on-treatment side effects but had the possibility to induce long-term treatment-related side effects. In contrast, low-dose chemotherapy has some on-treatment side effects and is known to have very low long-term toxicity. Thus, for progressive DTs following active surveillance, low-dose chemotherapy is recommended in young patients as long-term side effects are minor, whereas therapies such as sorafenib and pazopanib is recommended for older patients as early side effects are minor.
Topics: Humans; Vinorelbine; Sorafenib; Imatinib Mesylate; Hydroxyurea; Fibromatosis, Aggressive; Watchful Waiting; Methotrexate; Doxorubicin
PubMed: 35150408
DOI: 10.1007/s12306-022-00738-x -
Current Urology Reports Mar 2021To update epidemiological, diagnostic, and therapeutic information on primary synovial sarcoma of the kidney.
PURPOSE OF REVIEW
To update epidemiological, diagnostic, and therapeutic information on primary synovial sarcoma of the kidney.
RECENT FINDINGS
A total of 96 studies were analyzed; age at presentation was 38.6±14.2 years, predominant location of tumor was right kidney; frequent reported symptoms at diagnosis were hematuria and pain. For definitive diagnosis, cytogenetic technique was used. Detected oncogene was available in 37.8% cases with fusion of SS18-SSX in most patients. Surgery is treatment of choice, with adjuvant chemotherapy; most frequently ifosfamide-based associated with doxorubicin or epirubicin. Overall median survival was 34 months. Mortality was 29% of the cases which reported death and the recurrence rate was 39.8%. Risk of death was increased in patients with metastases at diagnosis Primary RSS occurs more often in young men. RSS often presents with symptoms and in an advanced stage. Surgical treatment is the most commonly used and chemotherapy for advanced or recurrent treatment.
Topics: Hematuria; Humans; Kidney Neoplasms; Neoplasm Recurrence, Local; Oncogene Proteins, Fusion; Pain; Sarcoma, Synovial; Survival Rate
PubMed: 33704587
DOI: 10.1007/s11934-021-01038-w -
The Lancet. Oncology Sep 2013Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-were not powered to test differences in overall survival. To guide treatment decisions in this population of patients, we did a systematic review and network meta-analysis to identify the best initial treatment strategy.
METHODS
We searched the Cochrane Library, Medline, and conference proceedings for randomised controlled trials published between January, 1980, and June, 2013, that assessed overall survival in patients with advanced-stage Hodgkin's lymphoma given BEACOPPbaseline, BEACOPPescalated, BEACOPP variants, ABVD, cyclophosphamide (mechlorethamine), vincristine, procarbazine, and prednisone (C[M]OPP), hybrid or alternating chemotherapy regimens with ABVD as the backbone (eg, COPP/ABVD, MOPP/ABVD), or doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (the Stanford V regimen). We assessed studies for eligibility, extracted data, and assessed their quality. We then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence. We also reconstructed individual patient survival data from published Kaplan-Meier curves and did standard random-effects Poisson regression. Results are reported relative to ABVD. The primary outcome was overall survival.
FINDINGS
We screened 2055 records and identified 75 papers covering 14 eligible trials that assessed 11 different regimens in 9993 patients, providing 59 651 patient-years of follow-up. 1189 patients died, and the median follow-up was 5·9 years (IQR 4·9-6·7). Included studies were of high methodological quality, and between-trial heterogeneity was negligible (τ(2)=0·01). Overall survival was highest in patients who received six cycles of BEACOPPescalated (HR 0·38, 95% credibility interval [CrI] 0·20-0·75). Compared with a 5 year survival of 88% for ABVD, the survival benefit for six cycles of BEACOPPescalated is 7% (95% CrI 3-10)-ie, a 5 year survival of 95%. Reconstructed individual survival data showed that, at 5 years, BEACOPPescalated has a 10% (95% CI 3-15) advantage over ABVD in overall survival.
INTERPRETATION
Six cycles of BEACOPPescalated significantly improves overall survival compared with ABVD and other regimens, and thus we recommend this treatment strategy as standard of care for patients with access to the appropriate supportive care.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 23948348
DOI: 10.1016/S1470-2045(13)70341-3 -
European Journal of Clinical... Nov 2023This study aimed to systematically review and critically appraise cost-effectiveness studies on Brentuximab vedotin (BV) in patients with Hodgkin lymphoma (HL). (Review)
Review
PURPOSE
This study aimed to systematically review and critically appraise cost-effectiveness studies on Brentuximab vedotin (BV) in patients with Hodgkin lymphoma (HL).
METHODS
The PubMed, Scopus, Web of Science core collection, and Embase databases were searched until July 3, 2022. We included published full economic evaluation studies on BV for treating patients with HL. The methodological quality of the studies was assessed using the Quality of Health Economic Studies (QHES) checklist. Meanwhile, we used qualitative synthesis to analyze the findings. We converted the incremental cost-effectiveness ratios (ICERs) to the value of the US dollar in 2022.
RESULTS
Eight economic evaluations met the study's inclusion criteria. The results of three studies that compared BV plus doxorubicin, vinblastine, and dacarbazine (BV + AVD) front-line therapy with doxorubicin, bleomycin, vincristine, and dacarbazine (ABVD) showed that BV is unlikely to be cost-effective as a front-line treatment in patients advanced stage (III or IV) HL. Four studies investigated the cost-effectiveness of BV in patients with relapsed or refractory (R/R) HL after autologous stem cell transplantation (ASCT). BV was not cost-effective in the reviewed studies at accepted thresholds. In addition, the adjusted ICERs ranged from $65,382 to $374,896 per quality-adjusted life-year (QALY). The key drivers of cost-effectiveness were medication costs, hazard ratio for BV, and utilities.
CONCLUSION
Available economic evaluations show that using BV as front-line treatment or consolidation therapy is not cost-effective based on specific ICER thresholds for patients with HL or R/R HL. To decide on this orphan drug, we should consider other factors such as existence of alternative treatment options, clinical benefits, and disease burden.
Topics: Humans; Hodgkin Disease; Brentuximab Vedotin; Cost-Benefit Analysis; Hematopoietic Stem Cell Transplantation; Doxorubicin; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Vinblastine; Dacarbazine; Transplantation, Autologous
PubMed: 37656182
DOI: 10.1007/s00228-023-03557-6 -
Echocardiography (Mount Kisco, N.Y.) Jul 2018Anthracyclines are widely used to treat solid and hematologic malignancies, but are known to cause cardiotoxicity. As more childhood cancer survivors reach adulthood due... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Anthracyclines are widely used to treat solid and hematologic malignancies, but are known to cause cardiotoxicity. As more childhood cancer survivors reach adulthood due to improvements in oncologic treatments, they become susceptible to late and progressive anthracycline-induced cardiotoxicity. Nonetheless, diagnostic criteria for early detection of cardiac dysfunction are not well defined in children, adolescent, and young adults (CAYA, ages 1-40 years). We present a natural history of the changes in myocardial deformation in CAYA patients after anthracycline therapy.
METHODS
We performed a literature review search between 2001 and 2016 using PubMed with the following search terms: strain (or deformation), torsion (or twist), children (or adolescent or young adult), cardiotoxicity (or dysfunction), and anthracyclines (or doxorubicin). A total of 23 articles were reviewed. Fourteen articles were incorporated in the meta-analysis.
RESULTS
Strain abnormalities are observed at both short-term and long-term follow-up. Global longitudinal strain (GLS) abnormalities are common during or early after chemotherapy, whereas changes in global circumferential strain (GCS) are more significant and consistent on long-term follow-up. Although global radial strain and torsional parameters are also often abnormal late after chemotherapy, there are few studies evaluating these parameters.
CONCLUSION
There are significant abnormalities in GLS and GCS following anthracycline therapy acutely and late after treatment. The prognostic value of these strain abnormalities warrants further investigation.
Topics: Adolescent; Adult; Anthracyclines; Cardiotoxicity; Child; Echocardiography, Three-Dimensional; Heart Ventricles; Humans; Neoplasms; Ventricular Dysfunction; Young Adult
PubMed: 29603386
DOI: 10.1111/echo.13871 -
Expert Review of Hematology Aug 2020To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess evidence on the safety and efficacy of ABVD (doxorubicin [Adriamycin®], bleomycin, vinblastine, and dacarbazine), BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), and A+AVD (brentuximab vedotin, with doxorubicin, vinblastine, and dacarbazine) for advanced-stage Hodgkin lymphoma (HL).
METHODS
A systematic literature review (SLR) was conducted on 29 July 2016 (updated 26 July 2018) to identify randomized controlled trials (RCTs) and non-RCTs assessing the treatment of newly-diagnosed advanced-stage HL with ABVD and BEACOPP (and their variants), and A+AVD.
RESULTS
The SLR identified 62 RCTs and 42 non-RCTs. Five-year overall survival rates for ABVD and BEACOPP were 60-97% and 84-99%, and 5-year progression-free survival rates were 58-81% and 83-96%, respectively. Both regimens were associated with tolerability issues and side effects. Discontinuation or dose reduction of bleomycin resulted in fewer adverse events, without significantly affecting efficacy. A head-to-head trial demonstrated improved efficacy for A+AVD vs ABVD, with an acceptable tolerability profile. No data from head-to-head trials comparing A+AVD with BEACOPP were available, and an indirect treatment comparison was not feasible.
CONCLUSION
New therapies, such as A+AVD, maintain the efficacy observed with current treatments, and may provide a more tolerable treatment option for patients with advanced-stage HL.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Diagnostic Imaging; Disease Management; Hodgkin Disease; Humans; Neoplasm Staging; Prognosis; Publication Bias; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32749937
DOI: 10.1080/17474086.2020.1793666 -
The Oncologist 2013CD30(+) lymphoproliferative disorders represent a spectrum of diseases with distinct clinical phenotypes ranging from reactive conditions to aggressive systemic... (Review)
Review
CD30(+) lymphoproliferative disorders represent a spectrum of diseases with distinct clinical phenotypes ranging from reactive conditions to aggressive systemic anaplastic lymphoma kinase (ALK)(-) anaplastic large cell lymphoma (ALCL). In January 2011, the U.S. Food and Drug Administration (FDA) announced a possible association between breast implants and ALCL, which was likened to systemic ALCL and treated accordingly. We analyzed existing data to see if implant-associated ALCL (iALCL) may represent a distinct entity, different from aggressive ALCL. We conducted a systematic review of publications regarding ALCL and breast implantation for 1990-2012 and contacted corresponding authors to obtain long-term follow-up where available. We identified 44 unique cases of iALCL, the majority of which were associated with seroma, had an ALK(-) phenotype (97%), and had a good prognosis, different from the expected 40% 5-year survival rate of patients with ALK(-) nodal ALCL (one case remitted spontaneously following implant removal; only two deaths have been reported to the FDA or in the scientific literature since 1990). The majority of these patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone with or without radiation, but radiation alone also resulted in complete clinical responses. It appears that iALCL demonstrates a strong association with breast implants, a waxing and waning course, and an overall good prognosis, with morphology, cytokine profile, and biological behavior similar to those of primary cutaneous ALCL. Taken together, these data are suggestive that iALCL may start as a reactive process with the potential to progress and acquire an aggressive phenotype typical of its systemic counterpart. A larger analysis and prospective evaluation and follow-up of iALCL patients are necessary to definitively resolve the issue of the natural course of the disease and best therapeutic approaches for these patients.
Topics: Adult; Aged; Aged, 80 and over; Breast Implantation; Female; Humans; Ki-1 Antigen; Lymphoma, Large-Cell, Anaplastic; Lymphoproliferative Disorders; Middle Aged
PubMed: 23429741
DOI: 10.1634/theoncologist.2012-0238 -
The American Journal of Cardiology Dec 2013The management of individual patients requiring anthracyclines remains challenging because uncertainty persists on predictors of cardiotoxicity. We aimed to perform a... (Meta-Analysis)
Meta-Analysis Review
The management of individual patients requiring anthracyclines remains challenging because uncertainty persists on predictors of cardiotoxicity. We aimed to perform a systematic review and meta-analysis on incidence and predictors of anthracycline chemotherapy in patients with cancer. Databases were searched for pertinent studies. Meta-analytic pooling with random-effects methods was performed for incidence estimates, while relying on descriptive statistics for prevalence and strength of association of predictors. From 16,054 retrieved citations, 18 studies reporting on 49,017 patients with cancer were included, with 22,815 treated with anthracyclines. After a median follow-up of 9 years, clinically overt cardiotoxicity occurred in 6% (95% confidence interval 3% to 9%), whereas subclinical cardiotoxicity developed in 18% (95% confidence interval 12% to 24%). Appraisal of independent risk factors of cardiotoxicity showed that cumulative anthracycline dose was most consistently reported as an accurate and robust predictor of cardiotoxicity, with an acceptable prognostic role also for chest radiotherapy, African-American ethnicity, very young or very old age, diabetes, hypertension, very high or very low body weight, or severe co-morbidities. In conclusion, despite ongoing refinements in chemotherapy regimens, anthracyclines still pose a significant risk of cardiotoxicity, especially in those requiring a high cumulative dose or chest radiotherapy.
Topics: Anthracyclines; Antibiotics, Antineoplastic; Comorbidity; Doxorubicin; Heart; Humans; Incidence; Neoplasms; Risk Factors
PubMed: 24075281
DOI: 10.1016/j.amjcard.2013.08.026 -
The Cochrane Database of Systematic... Jan 2013This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are malignant disorders of the placenta that include invasive hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Choriocarcinoma and invasive hydatidiform mole respond well to chemotherapy: low-risk tumours are treated with single-agent chemotherapy (e.g. methotrexate or actinomycin D), whereas high-risk tumours are treated with combination chemotherapy (e.g. EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine)). Various drug combinations may be used for high-risk tumours; however, the comparative efficacy and safety of these regimens is not clear.
OBJECTIVES
To determine the efficacy and safety of combination chemotherapy in treating high-risk GTN.
SEARCH METHODS
For the original review, we searched the Cochrane Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2008), MEDLINE, EMBASE and CBM in May 2008. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to September 2012. In addition, we searched online clinical trial registries for ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing first-line combination chemotherapy interventions in women with high-risk GTN.
DATA COLLECTION AND ANALYSIS
Two review authors independently collected data using a data extraction form. Meta-analysis could not be performed as we included only one study.
MAIN RESULTS
We included one RCT of 42 women with high-risk GTN who were randomised to MAC (methotrexate, actinomycin D and chlorambucil) or the modified CHAMOCA regimen (cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, doxorubicin, melphalan and vincristine). There were no statistically significant differences in efficacy of the two regimens; however women in the MAC group experienced statistically significantly less toxicity overall and less haematological toxicity than women in the CHAMOCA group. During the study period, six women in the CHAMOCA group died compared with one in the MAC group. This study was stopped early due to unacceptable levels of toxicity in the CHAMOCA group. We identified no RCTs comparing EMA/CO with MAC or other chemotherapy regimens.
AUTHORS' CONCLUSIONS
CHAMOCA is not recommended for GTN treatment as it is more toxic and not more effective than MAC. EMA/CO is currently the most widely used first-line combination chemotherapy for high-risk GTN, although this regimen has not been rigorously compared to other combinations such as MAC or FAV in RCTs. Other regimens may be associated with less acute toxicity than EMA/CO; however, proper evaluation of these combinations in high-quality RCTs that include long-term surveillance for secondary cancers is required. We acknowledge that, given the low incidence of GTN, RCTs in this field are difficult to conduct, hence multicentre collaboration is necessary.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Doxorubicin; Early Termination of Clinical Trials; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Hydroxyurea; Leucovorin; Melphalan; Methotrexate; Pregnancy; Trophoblastic Tumor, Placental Site; Vincristine
PubMed: 23440800
DOI: 10.1002/14651858.CD005196.pub4