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Journal of Cancer Research and... 2018The objective of this study was to perform a systematic review and meta-analysis to evaluate the two most commonly used chemotherapy regimens gemcitabine plus cisplatin... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
The objective of this study was to perform a systematic review and meta-analysis to evaluate the two most commonly used chemotherapy regimens gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin/adriamycin, and cisplatin (MVAC) regimens for muscle-invasive bladder cancer (MIBC) patients.
METHODS
We searched for all studies investigating GC and MVAC for MIBC patients in PubMed, Web of Knowledge, and the Cochrane Central Search Library. A systematic review and meta-analysis were performed.
RESULTS
Our searches identified 13 studies among 2174 patients. In the meta-analysis, the pathological complete response to GC regimens was superior to MVAC regimens. No significant difference in pathological partial response was found between the two groups. GC regimens were associated with a significant decrease risk in Grade 3-4 neutropenia, mucositis, and febrile neutropenia, but a significant increase risk in Grade 3-4 thrombocytopenia. There was no significant difference in overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) when compared GC regimens to MVAC regimens.
CONCLUSIONS
GC regimens significantly improved pathological complete response compared to MVAC regimens. GC regimens were associated with a significant decrease risk in Grade 3-4 neutropenia, mucositis, and febrile neutropenia, but a significant increase risk in Grade 3-4 thrombocytopenia. There was no significant difference in OS, DSS, and DFS when compared the two regimens.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Deoxycytidine; Doxorubicin; Humans; Methotrexate; Muscle Neoplasms; Neoplasm Invasiveness; Prognosis; Survival Rate; Urinary Bladder Neoplasms; Vinblastine; Gemcitabine
PubMed: 30488841
DOI: 10.4103/0973-1482.188434 -
Medicine Nov 2018Autophagy is a mechanism which relies on lysosomes for clearance and recycling of abnormal proteins or organelles. Many studies have demonstrated that the deregulation... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autophagy is a mechanism which relies on lysosomes for clearance and recycling of abnormal proteins or organelles. Many studies have demonstrated that the deregulation of autophagy is associated with the development of various diseases including cancer. The use of autophagy inhibitors is an emerging trend in cancer treatment. However, the value of autophagy inhibitors remains under debate. Thus, a meta-analysis was performed, aiming to evaluate the clinical value of autophagy-inhibitor-based therapy.
METHODS
We searched for clinical studies that evaluated autophagy-inhibitor-based therapy in cancer. We extracted data from these studies to evaluate the relative risk (RR) of overall response rate (ORR), 6-month progression-free survival (PFS) rate, and 1-year overall survival (OS) rate.
RESULTS
Seven clinical trials were identified (n = 293). Treatments included 2 combinations of hydroxychloroquine and gemcitabine, 1 combination of hydroxychloroquine and doxorubicin, 1 combination of chloroquine and radiation, 2 combinations of chloroquine, temozolomide, and radiation, and 1 hydroxychloroquine monotherapy. Autophagy-inhibitor-based therapy showed higher ORR (RR: 1.33, 95% confidence interval [CI]: 0.95-1.86, P = .009), PFS (RR: 1.72, 95% CI: 1.05-2.82, P = .000), OS (RR: 1.39, 95% CI: 1.11-1.75, P = .000) values than the therapy without inhibiting autophagy.
CONCLUSION
This meta-analysis showed that autophagy-inhibitor-based therapy has better treatment response compared to chemotherapy or radiation therapy without inhibiting autophagy, which may provide a new strategy for the treatment of cancers.
Topics: Antineoplastic Combined Chemotherapy Protocols; Autophagy; Chloroquine; Clinical Trials as Topic; Dacarbazine; Deoxycytidine; Doxorubicin; Humans; Hydroxychloroquine; Neoplasms; Risk; Temozolomide; Treatment Outcome; Gemcitabine
PubMed: 30431566
DOI: 10.1097/MD.0000000000012912 -
Clinical Lymphoma, Myeloma & Leukemia Dec 2018The 2 main formulations of anthracycline used for acute myeloid leukemia (AML) induction therapy are idarubicin (IDA) and daunorubicin. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The 2 main formulations of anthracycline used for acute myeloid leukemia (AML) induction therapy are idarubicin (IDA) and daunorubicin.
PATIENTS AND METHODS
The present systematic review and meta-analysis compared the efficacy and toxicity between IDA and high-dose daunorubicin (HDD) for induction therapy for adult AML. Relevant studies reported before June 2018 were searched from the Medline and Embase databases.
RESULTS
A total of 5 studies with 1809 participants (3 randomized controlled studies and 2 retrospective cohort studies) met the eligibility criteria and were included in the meta-analysis. The patients in the IDA arm for induction therapy had a significantly greater complete response rate after the first course of induction therapy compared with those in the HDD arm (66.7% vs. 61.1%, respectively; odds ratio, 1.23; P = .04; I = 0%). A significantly lower rate of refractory AML was also observed in the IDA group than in the HDD group (16.8% vs. 20.7%, respectively; odds ratio, 0.77; P = .04; I = 0%). However, no difference was found in the long-term overall survival between the 2 groups. Also, the induction mortality rate, febrile neutropenia rate, and cardiotoxicity rate were not significantly different between the 2 groups. The major limitation was the relatively small number of included studies, which could have limited the power of the meta-analysis to demonstrate significant long-term benefits.
CONCLUSION
The complete response rate after the first course of induction therapy was significantly greater among adult patients with AML who had received IDA as part of induction therapy compared with those who had received HDD.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Daunorubicin; Female; Humans; Idarubicin; Leukemia, Myeloid, Acute; Male; Middle Aged; Odds Ratio; Remission Induction; Treatment Outcome; Young Adult
PubMed: 30241991
DOI: 10.1016/j.clml.2018.08.008 -
Journal of Global Oncology Sep 2018Despite widespread use of fluorouracil, epirubicin, cyclophosphamide, docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary febrile... (Meta-Analysis)
Meta-Analysis
PURPOSE
Despite widespread use of fluorouracil, epirubicin, cyclophosphamide, docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary febrile neutropenia (FN) prophylaxis remains unknown. A systematic review was therefore performed.
METHODS
Embase, Ovid MEDLINE, PubMed, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, and conference proceedings were searched from 1946 to April 2016 for trials that reported the effectiveness of primary FN prophylaxis with FEC-D chemotherapy. Outcome measures were incidence of FN; treatment-related hospitalizations; chemotherapy dose delays, reductions, and discontinuations; and adverse events from prophylaxis.
RESULTS
Of 2,205 identified citations, eight studies (n = 1,250) met our eligibility criteria. Three additional studies (n = 293) were identified from a prior systematic review. Three randomized controlled trials (n = 576), one phase IV single-arm trial (n = 69), one prospective observational study (n = 37), and six retrospective studies (n = 861) were identified. Agents investigated were pegfilgrastim (n = 108), filgrastim (n = 1,119), and ciprofloxacin (n = 89). The heterogeneity of studies meant that a narrative synthesis of results was performed. Median FN rates for patients who received FEC-D with and without primary prophylaxis were 10.1% (interquartile range [IQR], 3.9% to 22.6%) and 23.9% (IQR, 9.2% to 27.3%), respectively. In the absence of primary prophylaxis, FN was more common during docetaxel than during FEC. Data from six studies showed a median rate of dose reductions and delays of 6.1% (IQR, 3.1% to 14.3%) and 19.3% (IQR, 10.5% to 32.8%), respectively, that occurred as a consequence of FN. Toxicity from prophylaxis itself was rarely reported.
CONCLUSION
Primary FN prophylaxis is effective in patients who receive FEC-D chemotherapy. The paucity of prospective data makes optimal recommendations about the choice and timing of prophylaxis challenging.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemoprevention; Cyclophosphamide; Docetaxel; Epirubicin; Febrile Neutropenia; Female; Fluorouracil; Humans; Risk Factors; Treatment Outcome
PubMed: 30241156
DOI: 10.1200/JGO.2016.008540 -
Scientific Reports Apr 2018Numerous studies have investigated the prognostic values of MYC and/or BCL2 protein overexpression in diffuse large B-cell lymphoma (DLBCL). However, the results still... (Meta-Analysis)
Meta-Analysis
Numerous studies have investigated the prognostic values of MYC and/or BCL2 protein overexpression in diffuse large B-cell lymphoma (DLBCL). However, the results still demonstrate discrepancies among different studies. We aimed to do a systematic review and meta-analysis on the relationships between overexpression MYC and/or BCL2 and DLBCLs treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). This study followed the guidelines of PRISMA and Cochrane handbook. The hazard ratios (HRs) for overall survival (OS) were pooled to estimate the main effect size. Twenty studies recruited a total of 5576 patients were available for this meta-analysis. The results showed that MYC (HR = 1.96, 95%CI (confidence interval) = 1.69-2.27)without heterogeneity(I = 17.2%, P = 0.280), BCL2 (HR = 1.65, 95%CI = 1.43-1.89, I = 20.7%, P = 0.234) protein overexpression, and co-overexpression (HR = 2.58, 95%CI = 2.19-3.04, I = 17.2%, P = 0.275) had a poor prognosis in R-CHOP treated DLBCL patients, respectively. The current analysis indicated that MYC and/or BCL2 protein overexpression, and particularly co-overexpression was related to short overall survival in R-CHOP treated DLBCL patients, showing that application of the two new biomarkers can help to better stratify DLBCL patients and guide targeted treatment.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Prednisone; Prognosis; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-myc; Rituximab; Survival Analysis; Vincristine
PubMed: 29674626
DOI: 10.1038/s41598-018-24631-5 -
The Cochrane Database of Systematic... Mar 2018Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic cancer (PC) is a highly lethal disease with few effective treatment options. Over the past few decades, many anti-cancer therapies have been tested in the locally advanced and metastatic setting, with mixed results. This review attempts to synthesise all the randomised data available to help better inform patient and clinician decision-making when dealing with this difficult disease.
OBJECTIVES
To assess the effect of chemotherapy, radiotherapy or both for first-line treatment of advanced pancreatic cancer. Our primary outcome was overall survival, while secondary outcomes include progression-free survival, grade 3/4 adverse events, therapy response and quality of life.
SEARCH METHODS
We searched for published and unpublished studies in CENTRAL (searched 14 June 2017), Embase (1980 to 14 June 2017), MEDLINE (1946 to 14 June 2017) and CANCERLIT (1999 to 2002) databases. We also handsearched all relevant conference abstracts published up until 14 June 2017.
SELECTION CRITERIA
All randomised studies assessing overall survival outcomes in patients with advanced pancreatic ductal adenocarcinoma. Chemotherapy and radiotherapy, alone or in combination, were the eligible treatments.
DATA COLLECTION AND ANALYSIS
Two review authors independently analysed studies, and a third settled any disputes. We extracted data on overall survival (OS), progression-free survival (PFS), response rates, adverse events (AEs) and quality of life (QoL), and we assessed risk of bias for each study.
MAIN RESULTS
We included 42 studies addressing chemotherapy in 9463 patients with advanced pancreatic cancer. We did not identify any eligible studies on radiotherapy.We did not find any benefit for chemotherapy over best supportive care. However, two identified studies did not have sufficient data to be included in the analysis, and many of the chemotherapy regimens studied were outdated.Compared to gemcitabine alone, participants receiving 5FU had worse OS (HR 1.69, 95% CI 1.26 to 2.27, moderate-quality evidence), PFS (HR 1.47, 95% CI 1.12 to 1.92) and QoL. On the other hand, two studies showed FOLFIRINOX was better than gemcitabine for OS (HR 0.51 95% CI 0.43 to 0.60, moderate-quality evidence), PFS (HR 0.46, 95% CI 0.38 to 0.57) and response rates (RR 3.38, 95% CI 2.01 to 5.65), but it increased the rate of side effects. The studies evaluating CO-101, ZD9331 and exatecan did not show benefit or harm when compared with gemcitabine alone.Giving gemcitabine at a fixed dose rate improved OS (HR 0.79, 95% CI 0.66 to 0.94, high-quality evidence) but increased the rate of side effects when compared with bolus dosing.When comparing gemcitabine combinations to gemcitabine alone, gemcitabine plus platinum improved PFS (HR 0.80, 95% CI 0.68 to 0.95) and response rates (RR 1.48, 95% CI 1.11 to 1.98) but not OS (HR 0.94, 95% CI 0.81 to 1.08, low-quality evidence). The rate of side effects increased. Gemcitabine plus fluoropyrimidine improved OS (HR 0.88, 95% CI 0.81 to 0.95), PFS (HR 0.79, 95% CI 0.72 to 0.87) and response rates (RR 1.78, 95% CI 1.29 to 2.47, high-quality evidence), but it also increased side effects. Gemcitabine plus topoisomerase inhibitor did not improve survival outcomes but did increase toxicity. One study demonstrated that gemcitabine plus nab-paclitaxel improved OS (HR 0.72, 95% CI 0.62 to 0.84, high-quality evidence), PFS (HR 0.69, 95% CI 0.58 to 0.82) and response rates (RR 3.29, 95% CI 2.24 to 4.84) but increased side effects. Gemcitabine-containing multi-drug combinations (GEMOXEL or cisplatin/epirubicin/5FU/gemcitabine) improved OS (HR 0.55, 95% CI 0.39 to 0.79, low-quality evidence), PFS (HR 0.43, 95% CI 0.30 to 0.62) and QOL.We did not find any survival advantages when comparing 5FU combinations to 5FU alone.
AUTHORS' CONCLUSIONS
Combination chemotherapy has recently overtaken the long-standing gemcitabine as the standard of care. FOLFIRINOX and gemcitabine plus nab-paclitaxel are highly efficacious, but our analysis shows that other combination regimens also offer a benefit. Selection of the most appropriate chemotherapy for individual patients still remains difficult, with clinicopathological stratification remaining elusive. Biomarker development is essential to help rationalise treatment selection for patients.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Deoxycytidine; Epirubicin; Fluorouracil; Humans; Paclitaxel; Pancreatic Neoplasms; Pyrimidines; Randomized Controlled Trials as Topic; Treatment Outcome; Gemcitabine
PubMed: 29557103
DOI: 10.1002/14651858.CD011044.pub2 -
The Cochrane Database of Systematic... Sep 2017Efficacy and the risk of severe late effects have to be well-balanced in treatment of Hodgkin lymphoma (HL). Late adverse effects include secondary malignancies which... (Meta-Analysis)
Meta-Analysis Review
Optimisation of chemotherapy and radiotherapy for untreated Hodgkin lymphoma patients with respect to second malignant neoplasms, overall and progression-free survival: individual participant data analysis.
BACKGROUND
Efficacy and the risk of severe late effects have to be well-balanced in treatment of Hodgkin lymphoma (HL). Late adverse effects include secondary malignancies which often have a poor prognosis. To synthesise evidence on the risk of secondary malignancies after current treatment approaches comprising chemotherapy and/or radiotherapy, we performed a meta-analysis based on individual patient data (IPD) from patients treated for newly diagnosed HL.
OBJECTIVES
We investigated several questions concerning possible changes in the risk of secondary malignancies when modifying chemotherapy or radiotherapy (omission of radiotherapy, reduction of the radiation field, reduction of the radiation dose, use of fewer chemotherapy cycles, intensification of chemotherapy). We also analysed whether these modifications affect progression-free survival (PFS) and overall survival (OS).
SEARCH METHODS
We searched MEDLINE and Cochrane CENTRAL trials databases comprehensively in June 2010 for all randomised trials in HL since 1984. Key international trials registries were also searched. The search was updated in March 2015 without collecting further IPD (one further eligible study found) and again in July 2017 (no further eligible studies).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) for untreated HL patients which enrolled at least 50 patients per arm, completed recruitment by 2007 and performed a treatment comparison relevant to our objectives.
DATA COLLECTION AND ANALYSIS
Study groups submitted IPD, including age, sex, stage and the outcomes secondary malignant neoplasm (SMN), OS and PFS as time-to-event data. We meta-analysed these data using Petos method (SMN) and Cox regression with inverse-variance pooling (OS, PFS) for each of the five study questions, and performed subgroup and sensitivity analyses to assess the applicability and robustness of the results.
MAIN RESULTS
We identified 21 eligible trials and obtained IPD for 16. For four studies no data were supplied despite repeated efforts, while one study was only identified in 2015 and IPD were not sought. For each study question, between three and six trials with between 1101 and 2996 participants in total and median follow-up between 6.7 and 10.8 years were analysed. All participants were adults and mainly under 60 years. Risk of bias was assessed as low for the majority of studies and outcomes. Chemotherapy alone versus same chemotherapy plus radiotherapy. Omitting additional radiotherapy probably reduces secondary malignancy incidence (Peto odds ratio (OR) 0.43, 95% confidence interval (CI) 0.23 to 0.82, low quality of evidence), corresponding to an estimated reduction of eight-year SMN risk from 8% to 4%. This decrease was particularly true for secondary acute leukemias. However, we had insufficient evidence to determine whether OS rates differ between patients treated with chemotherapy alone versus combined-modality (hazard ratio (HR) 0.71, 95% CI 0.46 to 1.11, moderate quality of evidence). There was a slightly higher rate of PFS with combined modality, but our confidence in the results was limited by high levels of statistical heterogeneity between studies (HR 1.31, 95% CI 0.99 to 1.73, moderate quality of evidence). Chemotherapy plus involved-field radiation versus same chemotherapy plus extended-field radiation (early stages) . There is insufficient evidence to determine whether smaller radiation field reduces SMN risk (Peto OR 0.86, 95% CI 0.64 to 1.16, low quality of evidence), OS (HR 0.89, 95% C: 0.70 to 1.12, high quality of evidence) or PFS (HR 0.99, 95% CI 0.81 to 1.21, high quality of evidence). Chemotherapy plus lower-dose radiation versus same chemotherapy plus higher-dose radiation (early stages). There is insufficient evidence to determine the effect of lower-radiation dose on SMN risk (Peto OR 1.03, 95% CI 0.71 to 1.50, low quality of evidence), OS (HR 0.91, 95% CI 0.65 to 1.28, high quality of evidence) or PFS (HR 1.20, 95% CI 0.97 to 1.48, high quality of evidence). Fewer versus more courses of chemotherapy (each with or without radiotherapy; early stages). Fewer chemotherapy courses probably has little or no effect on SMN risk (Peto OR 1.10, 95% CI 0.74 to 1.62), OS (HR 0.99, 95% CI 0.73 to1.34) or PFS (HR 1.15, 95% CI 0.91 to 1.45).Outcomes had a moderate (SMN) or high (OS, PFS) quality of evidence. Dose-intensified versus ABVD-like chemotherapy (with or without radiotherapy in each case). In the mainly advanced-stage patients who were treated with intensified chemotherapy, the rate of secondary malignancies was low. There was insufficient evidence to determine the effect of chemotherapy intensification (Peto OR 1.37, CI 0.89 to 2.10, low quality of evidence). The rate of secondary acute leukemias (and for younger patients, all secondary malignancies) was probably higher than among those who had treatment with standard-dose ABVD-like protocols. In contrast, the intensified chemotherapy protocols probably improved PFS (eight-year PFS 75% versus 69% for ABVD-like treatment, HR 0.82, 95% CI 0.7 to 0.95, moderate quality of evidence). Evidence suggesting improved survival with intensified chemotherapy was not conclusive (HR: 0.85, CI 0.70 to 1.04), although escalated-dose BEACOPP appeared to lengthen survival compared to ABVD-like chemotherapy (HR 0.58, 95% CI 0.43 to 0.79, moderate quality of evidence).Generally, we could draw valid conclusions only in terms of secondary haematological malignancies, which usually occur less than 10 years after initial treatment, while follow-up within the present analysis was too short to record all solid tumours.
AUTHORS' CONCLUSIONS
The risk of secondary acute myeloid leukaemia and myelodysplastic syndrome (AML/MDS) is increased but efficacy is improved among patients treated with intensified chemotherapy protocols. Treatment decisions must be tailored for individual patients. Consolidating radiotherapy is associated with an increased rate of secondary malignancies; therefore it appears important to define which patients can safely be treated without radiotherapy after chemotherapy, both for early and advanced stages. For early stages, treatment optimisation methods such as use of fewer chemotherapy cycles and reduced field or reduced-dose radiotherapy did not appear to markedly affect efficacy or secondary malignancy risk. Due to the limited amount of long-term follow-up in this meta-analysis, further long-term investigations of late events are needed, particularly with respect to secondary solid tumours. Since many older studies have been included, possible improvement of radiotherapy techniques must be considered when interpreting these results.
Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemoradiotherapy; Dacarbazine; Disease-Free Survival; Doxorubicin; Hodgkin Disease; Humans; Leukemia, Radiation-Induced; Middle Aged; Myelodysplastic Syndromes; Neoplasms, Second Primary; Radiotherapy; Radiotherapy Dosage; Randomized Controlled Trials as Topic; Vinblastine
PubMed: 28901021
DOI: 10.1002/14651858.CD008814.pub2 -
The Oncologist Dec 2017Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8-12 months. The role of second-line therapy has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prognosis for patients with metastatic soft tissue sarcomas (STS) is dismal, with median overall survival (OS) of 8-12 months. The role of second-line therapy has been inconsistently investigated over the last 20 years. This systematic review and meta-analysis was performed to assess the efficacy of salvage treatment in pretreated adult type STS, gastrointestinal stromal tumor (GIST) excluded.
MATERIAL AND METHODS
PubMed, Web of Science, SCOPUS, EMBASE, CINAHL, and The Cochrane Library were searched for randomized phase II/phase III trials exploring second- or beyond therapy lines in pretreated metastatic STS. Two independent investigators extracted data; the quality of eligible studies was resolved by consensus. Hazard ratio (HR) of death and progression (OS and progression-free survival [PFS]) and odds ratio (OR) for response rate (RR) were pooled in a fixed- or random-effects model according to heterogeneity. Study quality was assessed with the Cochrane's risk of bias tool, and publication bias with funnel plots.
RESULTS
Overall, 10 randomized trials were selected. The pooled HR for death was 0.81 (95% confidence interval [CI] 0.73-0.9). Second-line therapy reduced the risk of progression by 49% (HR = 0.51, 95% CI 0.34-0.76). This translated into an absolute benefit in OS and PFS by 3.3 and 1.6 months, respectively. Finally, RR with new agents or chemotherapy doublets translated from 4.3% to 7.6% (OR = 1.78, 95% CI 1.22-2.50).
CONCLUSION
Better survival is achieved in patients treated with salvage therapies (chemotherapy, as single or multiple agents or targeted biological agents). A 3-months gain in OS and an almost double RR is observed. Second lines also attained a reduction by 50% the risk of progression.
IMPLICATIONS FOR PRACTICE
There is some evidence that salvage therapies after first-line failure are able to improve outcome in metastatic soft tissue sarcoma (STS). Trabectedin, gemcitabine-based therapy, and pazopanib are currently approved drugs used after conventional upfront treatment. This meta-analysis reviews the benefit of new agents used in randomized trials in comparison with no active treatments or older agents for recurrent/progressed STS. The results show that modern drugs confer a statistically significant 3-month benefit in terms of overall survival, and an increase in response rate. Despite a limited improvement in outcome, currently approved second-line therapy should be offered to patients with good performance status.
Topics: Disease-Free Survival; Doxorubicin; Humans; Randomized Controlled Trials as Topic; Salvage Therapy; Sarcoma
PubMed: 28835514
DOI: 10.1634/theoncologist.2016-0474 -
The Cochrane Database of Systematic... May 2017There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP... (Meta-Analysis)
Meta-Analysis Review
Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma.
BACKGROUND
There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen.
OBJECTIVES
To determine the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD in the treatment of early unfavourable or advanced stage HL as first-line treatment.
SEARCH METHODS
We searched for randomised controlled trials in MEDLINE, CENTRAL and conference proceedings (January 1985 to July 2013 and for the update to March 2017) and Embase (1985 to November 2008). Moreover we searched trial registries (March 2017; www.controlled-trials.com, www.clinicaltrialsregister.eu/ctr-search/search, clinicaltrials.gov, www.eortc.be, www.ghsg.org, www.ctc.usyd.edu.au, www.trialscentral.org/index.html) SELECTION CRITERIA: We included randomised controlled trials examining chemotherapy including at least two cycles of escalated BEACOPP regimens compared with chemotherapy including at least four cycles of ABVD regimens as first-line treatment for patients with early unfavourable stage or advanced stage HL.
DATA COLLECTION AND ANALYSIS
The effect measures we used were hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS) and freedom from first progression.We used risk ratios (RRs) relative risks to analyse harms: treatment-related mortality, secondary malignancies (including myeloid dysplastic syndrome (MDS) or acute myeloid leukaemia (AML)), infertility and adverse events.Quality of life was not reported in any trial, therefore not analysed. Two review authors independently extracted data and assessed quality of trials.
MAIN RESULTS
We screened 1796 records and identified five eligible trials in total i.e. one trial could be added on the previous review. These trials included only adults (16 to 65 years of age). We included all five trials with 3427 people in the meta-analyses: the HD9 and HD14 trials were co-ordinated in Germany, the HD2000 and GSM-HD trials were performed in Italy and the EORTC 20012 was conducted in Belgium. The overall risk of performance and detection bias was low for overall survival (OS), but was high for other outcomes, as therapy blinding was not feasible. The remaining 'Risk of bias' domains were low and unclear.All trials reported results for OS and progression-free survival (PFS). In contrast to the our first published review (2011) the addition of results from the EORTC 20012 BEACOPP escalated increases OS (3142 participants; HR 0.74 (95% confidence interval (CI) 0.57 to 0.97; high-quality evidence). This means that only 90 (70 to 117) patients will die after five years in the BEACOPP escalated arm compared to 120 in the ABVD arm. This survival advantage is also reflected in an increased PFS with BEACOPP escalated (3142 participants; HR 0.54 (95% CI 0.45 to 0.64); moderate-quality evidence), meaning that after five years only 144 (121 to 168) patients will experience a progress, relapse or death in the BEACOPP escalated arm compared to 250 in the ABVD arm.There is no evidence for a difference for treatment-related mortality (2700 participants, RR 2.15 (95% CI = 0.93 to 4.95), low-quality evidence).Although the occurrence of MDS or AML may increase with BEACOPP escalated (3332 participants, RR 3.90 (95% CI 1.36 to 11.21); low-quality evidence)), there is no evidence for a difference between both regimens for overall secondary malignancies (3332 participants, RR 1.00 (95% CI 0.68 to 1.48), low-quality evidence). However, the observation time of the studies included in the review is too short to be expected to demonstrate differences with respect to second solid tumours which would not be expected to show significance until around 15 years after treatment.We are very uncertain how many female patients will be infertile due to chemotherapy and which arm might be favoured (106 participants, RR 1.37 (95% CI 0.83 to 2.26), very low-quality evidence). This is a very small sample, and the age of the patients was not detailed. No analysis of male fertility was provided.Five trials reported adverse events and the analysis shows that the escalated BEACOPP regimens probably causes more haematological toxicities WHO grade III or IV ((anaemia: 2425 participants, RR 10.67 (95% CI 7.14 to 15.93); neutropenia: 519 participants, RR 1.80 (95% CI 1.52 to 2.13); thrombocytopenia: 2425 participants, RR 18.12 (95% CI 11.77 to 27.92); infections: 2425 participants, RR 3.73 (95% CI 2.58 to 5.38), all low-quality evidence).Only one trial (EORTC 20012) planned to assess quality of life, however, no results were reported.
AUTHORS' CONCLUSIONS
This meta-analysis provides moderate- to high-quality evidence that adult patients between 16 and 60 years of age with early unfavourable and advanced stage HL benefit regarding OS and PFS from first-line chemotherapy including escalated BEACOPP. The proven benefit in OS for patients with advanced HL is a new finding of this updated review due to the inclusion of the results from the EORTC 20012 trial. Furthermore, there is only low-quality evidence of a difference in the total number of secondary malignancies, as the follow-up period might be too short to detect meaningful differences. Low-quality evidence also suggests that people treated with escalated BEACOPP may have a higher risk to develop secondary AML or MDS. Due to the availability of only very low-quality evidence available, we are unable to come to a conclusion in terms of infertility. This review does for the first time suggest a survival benefit. However, it is clear from this review that BEACOPP escalated may be more toxic that ABVD, and very important long-term side effects of second malignancies and infertility have not been sufficiently analysed yet.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Disease Progression; Doxorubicin; Etoposide; Hodgkin Disease; Humans; Middle Aged; Prednisone; Procarbazine; Randomized Controlled Trials as Topic; Vinblastine; Vincristine; Young Adult
PubMed: 28541603
DOI: 10.1002/14651858.CD007941.pub3 -
The Neurologist Nov 2016There are increasing reports of posterior reversible encephalopathy syndrome (PRES) associated with the use of chemotherapeutic agents. Recognition of PRES is crucial... (Review)
Review
INTRODUCTION
There are increasing reports of posterior reversible encephalopathy syndrome (PRES) associated with the use of chemotherapeutic agents. Recognition of PRES is crucial given its reversibility with appropriate supportive management. We report a patient presenting with PRES after treatment with Rituximab, Cyclophosphamide, Hydroxydaunorubicin/Adriamycin, Oncovin/Vincristine, Prednisone (R-CHOP) and intrathecal methotrexate. We also perform a systematic review of the literature on chemotherapy-associated PRES.
CASE REPORT
A 72-year-old man with recently diagnosed diffuse large B-cell lymphoma became unresponsive 4 days after initiation of R-CHOP and intrathecal methotrexate. Brain magnetic resonance imaging showed interval development of occipital and temporal fluid attenuation inversion recovery hyperintensities consistent with PRES. The patient's blood pressure was aggressively controlled and he received 5 days of high-dose methylprednisone. He subsequently regained consciousness and his mental status gradually improved. Repeat magnetic resonance imaging showed interval resolution of the bilateral fluid attenuation inversion recovery hyperintensities.
REVIEW SUMMARY
We performed a systematic review of the literature and included a total of 70 unique cases involving chemotherapy-associated PRES. Platinum-containing drugs, Cyclophosphamide, Hydroxydaunorubicin/Adriamycin, Oncovin/Vincristine, Prednisone/R-CHOP regimens, and gemcitabine were the agents most commonly used in patients who developed suspected chemo-associated PRES. Median onset of symptoms occurred 8 days after chemotherapy. Hypertension was the most commonly reported risk factor associated with the development of chemotherapy-associated PRES. In most cases, PRES improved with supportive management alone within 2 weeks.
CONCLUSIONS
Chemotherapy-associated PRES is an increasingly encountered syndrome. Both neurologists and non-neurologists should be familiar with the most commonly implicated agents, symptoms, risk factors, and clinical course of chemotherapy-associated PRES, given its favorable prognosis with appropriate management.
Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Brain; Cyclophosphamide; Doxorubicin; Humans; Infusions, Spinal; Lymphoma, Large B-Cell, Diffuse; Magnetic Resonance Imaging; Male; Methotrexate; Posterior Leukoencephalopathy Syndrome; Prednisone; Rituximab; Vincristine
PubMed: 27801773
DOI: 10.1097/NRL.0000000000000105