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The Cochrane Database of Systematic... 2003Considerable controversy exists as to whether any benefit of doxorubicin-based combination chemotherapy outweighs increased toxic effects, inconvenience, and additional... (Review)
Review
BACKGROUND
Considerable controversy exists as to whether any benefit of doxorubicin-based combination chemotherapy outweighs increased toxic effects, inconvenience, and additional costs, compared to single-agent doxorubicin. There is substantial variation in clinical practice in the treatment of patients with locally advanced and metastatic soft tissue sarcoma (STS).
OBJECTIVES
To determine:1) the effect, if any on response rate or survival, by using doxorubicin-based combination chemotherapy compared with single-agent doxorubicin for the treatment of patients with incurable locally advanced or metastatic STS2)if combination chemotherapy is associated with increased adverse effects compared with single-agent doxorubicin in this setting.
SEARCH STRATEGY
We searched CENTRAL (Cochrane Library, issue 4, 2002), MEDLINE (1966 to October 2002), CANCER LIT (1975 to October 2002), reference lists, the Physician Data Query (PDQ) clinical trials database, and the American Society of Clinical Oncology (ASCO) Annual Meeting Proceedings (1995 to 2002).
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing single-agent doxorubicin with doxorubicin-based combination chemotherapy in adults with locally advanced or metastatic STS requiring palliative chemotherapy. Abstracts and full reports published in English were eligible.
DATA COLLECTION AND ANALYSIS
Data were abstracted and assessed by two reviewers. Response and survival data were pooled. Data on adverse effects was tabulated.
MAIN RESULTS
Data on 2281 participants from eight RCTs were available from reports of single-agent doxorubicin versus doxorubicin-based combination chemotherapy. Meta-analysis using the fixed effect model detected a higher tumour response rate with combination chemotherapy compared with single-agent chemotherapy (odds ratio [OR= 1.29; 95% confidence interval [CI], 1.03 to 1.60; p = 0.03), but the OR from a pooled analysis using the random effects model and the same data did not achieve statistical significance (OR= 1.26; 95% CI, 0.96 to 1.67; p = 0.10). No significant difference between the two regimens was detected in the pooled one-year mortality rate (OR = 0.87; 95% CI, 0.73 to 1.05; p=0.14) or two-year mortality rate (OR = 0.84; 95% CI, 0.67 to 1.06; p=0.13) (N=2097). Although reporting of adverse effects was limited and inconsistent among trials (making pooling of data for this outcome impossible), adverse effects such as nausea/vomiting and hematologic toxic effects were consistently reported as being worse with combination chemotherapy across the eight eligible studies.
REVIEWER'S CONCLUSIONS
Compared to single-agent doxorubicin, the combination chemotherapy regimens evaluated, given in conventional doses, produced only marginal increases in response rates, at the expense of increased toxic effects and with no improvements in overall survival.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Humans; Palliative Care; Sarcoma
PubMed: 12917960
DOI: 10.1002/14651858.CD003293 -
Blood Advances May 2021The dilemma of whether to treat elderly patients with diffuse large B-cell lymphoma (DLBCL) with a full or reduced dose intensity (DI) of R-CHOP (cyclophosphamide,...
The dilemma of whether to treat elderly patients with diffuse large B-cell lymphoma (DLBCL) with a full or reduced dose intensity (DI) of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone+rituximab) is often faced by clinicians. We conducted a systematic review assessing the impact of R-CHOP DI on DLBCL survival outcomes, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols (PRISMA-P) guidelines. We searched MEDLINE, EMBASE, and Cochrane CENTRAL for studies with ≥100 patients treated with R-CHOP/R-CHOP-like therapies published from January 2002 through November 2020. Studies were included if they reported the impact of R-CHOP DI on survival outcomes. We screened records, extracted data, and reviewed all the studies for quality and statistical appraisal. Of 380 screened records, 13 studies including 5188 patients were reviewed. DI was often calculated as the ratio of the cumulative delivered dose of prespecified drug(s) to the cumulative planned dose multiplied by a time-correction factor. Lower DI (intended or relative) was associated with inferior survival in 7 of 9 studies reporting crude survival analyses. Multivariable analysis using DI as a covariate was performed in 10 studies. Six showed an association (P < .05) with adjustment for other covariates, and 4 did not. Most studies and those larger studies of higher quality showed poorer outcomes associated with reduced DI. In subgroups aged ≥80 years, survival was not consistently affected by reduced DI. DI-specific randomized trials are warranted, but these data support full-dose R-CHOP in elderly and fit patients aged <80 years with DLBCL, but not in those aged ≥80 years, where dose-reduced R-CHOP does not appear to compromise survival.
Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Rituximab; Vincristine
PubMed: 33961018
DOI: 10.1182/bloodadvances.2021004665 -
Medicine Aug 2021It is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is well known that liposome-based delivery of cytotoxic chemotherapeutics has been proposed as a putative strategy to enhance drug tolerability and efficacy compared to the conventional chemotherapy. However, its potential effect on improving prognosis remains largely unknown. The current meta-analysis is to explore the prognosis of cancer patients undergoing liposomal doxorubicin-based chemotherapy.
METHODS
A detailed review of English and Chinese literature was conducted up to March 21, 2020. We evaluate its possible correlations using hazard ratios (HRs) with 95% confidence intervals (CIs). The pooled data were calculated by STATA software and Review Manager 5.3 software.
RESULTS
Consequently, 26 studies including 7943 patients were satisfied in current analysis. There were no significant differences between liposomal and conventional chemotherapy in OS (HR = 0.98, 95%CI: 0.93-1.04, P = .544) and PFS (HR = 1.00, 95%CI: 0.92-1.10, P = .945). Likewise, subgroup-analysis regarding country, cancer type, and sample sizes also showed the similar results of the 2 paired groups.
CONCLUSION
Taken together, our finding has demonstrated that there was no association of undergoing liposomal doxorubicin-based chemotherapy with cancer prognosis. However, detailed and further studies are needed to confirm our conclusion.
Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Humans; Multicenter Studies as Topic; Neoplasms; Polyethylene Glycols; Proportional Hazards Models; Randomized Controlled Trials as Topic
PubMed: 34449454
DOI: 10.1097/MD.0000000000026690 -
Medical Archives (Sarajevo, Bosnia and... Jun 2022Bladder cancer is still a burden on the world of oncology medicine, which every year affects about 3.4 million people globally with 430,000 new cases per year. It is the... (Meta-Analysis)
Meta-Analysis
Comparison Between Intravesical Chemotherapy Epirubicin and Mitomycin-C after TURB vs TURB Alone With Recurrence Rate of Non-Muscle Invasive Bladder Cancer: Meta-Analysis.
BACKGROUND
Bladder cancer is still a burden on the world of oncology medicine, which every year affects about 3.4 million people globally with 430,000 new cases per year. It is the fourth most common cancer in men and eighth most common women malignancy in the world. This makes bladder cancer a "silent killer" and it needs appropriate treatment planning. Single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB) is recommended by EAU guideline, but its use remains a controversy.
OBJECTIVE
Study aimed to analyze benefit of intravesical chemotherapy following TURB in terms of recurrency of non-muscle invasive bladder cancer (NMIBC).
METHODS
Systematic review and meta-analysis of randomized controlled trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC (pTa-pT1) patients was conducted. Studies searched throughout Medline, PubMed, Embase, and Cochrane in December 2018. Keywords were intravesical chemotherapy, combination, transurethral resection, bladder cancer. Inclusion criteria were RCT studies, subjects in study were treated single immediate chemotherapy instillation after TURB compared to TURB alone in patient with pTa-pT1 urothelial carcinoma of the bladder. Trials with additional treatment prior to first reccurence were not eligible. Studies using recurrence rate as dependent variable. From 361 studies, in total 11 studies were eligible for this meta-analysis.
RESULTS
From those 11 studies, it is shown that intravesical chemotherapy using Epirubicin and Mitomycin-C following TURB showed significant decrease of recurrence rate of bladder cancer even to progression of the disease compared to TURB alone (p<0.05) with pooled Risk Ratio were 0.69 and pooled heterogeneity (I) were 26.6%.
CONCLUSION
This meta-analysis study showed that combination therapy of intravesical chemotherapy after TURB is superior to TURB alone in showing the recurrence rate of NMIBC.
Topics: Administration, Intravesical; Carcinoma, Transitional Cell; Epirubicin; Female; Humans; Male; Mitomycin; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Urinary Bladder Neoplasms
PubMed: 36200115
DOI: 10.5455/medarh.2022.76.198-201 -
PloS One 2021To compare the effectiveness and safety of intensive antileukemic therapy to less-intensive therapy in older adults with acute myeloid leukemia (AML) and intermediate or...
To compare the effectiveness and safety of intensive antileukemic therapy to less-intensive therapy in older adults with acute myeloid leukemia (AML) and intermediate or adverse cytogenetics, we searched the literature in Medline, Embase, and CENTRAL to identify relevant studies through July 2020. We reported the pooled hazard ratios (HRs), risk ratios (RRs), mean difference (MD) and their 95% confidence intervals (CIs) using random-effects meta-analyses and the certainty of evidence using the GRADE approach. Two randomized trials enrolling 529 patients and 23 observational studies enrolling 7296 patients proved eligible. The most common intensive interventions included cytarabine-based intensive chemotherapy, combination of cytarabine and anthracycline, or daunorubicin/idarubicin, and cytarabine plus idarubicin. The most common less-intensive therapies included low-dose cytarabine alone, or combined with clofarabine, azacitidine, and hypomethylating agent-based chemotherapy. Low certainty evidence suggests that patients who receive intensive versus less-intensive therapy may experience longer survival (HR 0.87; 95% CI, 0.76-0.99), a higher probability of receiving allogeneic hematopoietic stem cell transplantation (RR 6.14; 95% CI, 4.03-9.35), fewer episodes of pneumonia (RR, 0.25; 95% CI, 0.06-0.98), but a greater number of severe, treatment-emergent adverse events (RR, 1.34; 95% CI, 1.03-1.75), and a longer duration of intensive care unit hospitalization (MD, 6.84 days longer; 95% CI, 3.44 days longer to 10.24 days longer, very low certainty evidence). Low certainty evidence due to confounding in observational studies suggest superior overall survival without substantial treatment-emergent adverse effect of intensive antileukemic therapy over less-intensive therapy in older adults with AML who are candidates for intensive antileukemic therapy.
Topics: Aged; Humans; Leukemia, Myeloid, Acute; Survival Analysis
PubMed: 33784346
DOI: 10.1371/journal.pone.0249087 -
Blood Cancer Journal Jan 2022Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We... (Meta-Analysis)
Meta-Analysis
Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a random-effects Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Progression-free survival (PFS) was compared between 11 modern regimens with different immunochemotherapy and maintenance strategies. G-Benda-G resulted in with the best PFS, with an HR of 0.41 compared to R-Benda, a surface under the cumulative ranking curve (SUCRA) of 0.97, a probability of being the best treatment (PbBT) of 72%, and a posterior ranking distribution (PoRa) of 1 (95% BCI 1-3). This was followed by R-Benda-R4 (HR = 0.49, PbBT = 25%, PoRa = 2) and R-Benda-R (HR = 0.60, PbBT = 3%, PoRa = 3). R-CHOP-R (HR = 0.96) and R-Len-R (HR = 0.97) had similar efficacy to R-Benda. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR = 0.62; G-Benda-G vs G-CHOP-G, HR = 0.55) or without maintenance therapy (R-Benda vs R-CHOP, HR = 0.68). Rituximab maintenance improved PFS following R-CHOP (R-CHOP-R vs R-CHOP, HR = 0.65) or R-Benda (R-Benda-R vs R-Benda, HR = 0.60; R-Benda-R4 vs R-Benda, HR = 0.49). In the absence of multi-arm RCTs that include all common regimens, this NMA provides an important and useful guide to inform treatment decisions.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Cyclophosphamide; Doxorubicin; Humans; Immunotherapy; Lymphoma, Follicular; Maintenance Chemotherapy; Prednisone; Progression-Free Survival; Randomized Controlled Trials as Topic; Rituximab; Treatment Outcome; Vincristine
PubMed: 34987165
DOI: 10.1038/s41408-021-00598-x -
Medicine Aug 2023Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess... (Meta-Analysis)
Meta-Analysis
Novel-fosfamide monotherapy or in combination with doxorubicin versus doxorubicin alone in patients with advanced soft tissue sarcoma: A pooled analysis of randomized clinical trials.
BACKGROUND
Novel-fosfamides (NFOs) belong to active metabolites of ifosfamide that bypass the generation of toxic byproducts. In this analysis, we aimed to comprehensively assess the benefits and risks of NFO monotherapy or in combination with doxorubicin (DOX) versus single-drug DOX in previously untreated patients with advanced soft-tissue sarcoma (ASTS).
METHODS
Online PubMed, Web of Science, Embase, and Cochrane CENTRAL databases were systematically searched on April 26, 2022. Objective response rate and disease control rate were primary outcomes. Overall survival (OS), progression-free survival (PFS), and grade ≥ 3 treatment-related adverse events were secondary outcomes.
RESULTS
In all, 3 randomized clinical trials with a total of 1207 ASTS patients were eligible. DOX plus NFO combination therapy showed higher risk ratios of objective response rate (1.50, 95% CI 1.20-1.68, P = .0003) and disease control rate (1.15, 95% CI 1.05-1.27, P = .0030) compared with DOX monotherapy. Nevertheless, NFO-based monotherapy and combination therapy were found no improvements on OS (hazard ratio 0.93, 95% CI 0.52-1.65, P = .8050) and PFS (hazard ratio 0.88, 95% CI 0.54-1.43, P = .6088) against DOX. More incidences of grade 3 or worse anemia, thrombocytopenia, stomatitis, diarrhea, constipation, and febrile neutropenia were observed in NFO-based treatments.
CONCLUSION
Adding NFO to DOX as first-line therapy improved the responses in ASTS patients but did not prolong OS and PFS. Grade 3 or worse treatment-related adverse events should be treated with caution during the NFO-based therapies.
Topics: Humans; Randomized Controlled Trials as Topic; Doxorubicin; Soft Tissue Neoplasms; Sarcoma; Thrombocytopenia
PubMed: 37603507
DOI: 10.1097/MD.0000000000034902 -
Health Technology Assessment... 2002
Review
Topics: Aged; Antineoplastic Agents; Cost-Benefit Analysis; Doxorubicin; Female; Humans; Middle Aged; Outcome Assessment, Health Care; Ovarian Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; State Medicine; Survival; United Kingdom
PubMed: 12433314
DOI: 10.3310/hta6230 -
World Journal of Surgical Oncology Feb 2021Isolated primary sacral diffuse large B cell non-Hodgkin's lymphoma is a very rare entity, and only 11 cases have been reported previously.
INTRODUCTION
Isolated primary sacral diffuse large B cell non-Hodgkin's lymphoma is a very rare entity, and only 11 cases have been reported previously.
CASE PRESENTATION
A 36-year-old man was referred with low backache and radiculopathy pain with a clinico-radiological and cytological diagnosis of sacral metastasis. Histopathological examination and immunohistochemistry of image-guided tissue core biopsy from the sacral mass confirmed it as high-grade diffuse large B cell lymphoma (DLBCL). With normal blood counts and bone marrow, and no lesions elsewhere on imaging, he was staged IAE and received 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen chemotherapy followed by radiotherapy. The patient has completed a 3-year follow-up and is doing well with yearly imaging showing no evidence of active disease or recurrence.
CONCLUSIONS
The case shows the importance of an image-guided core biopsy and immunohistochemistry over a fine needle aspiration cytology in select cases as it can alter the treatment and outcome in patients. Because of rarity, the treatment and prognosis in primary sacral NHL is not still very clear as it is treated as per the guidelines of treatment of bone lymphoma.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Neoplasm Recurrence, Local; Prognosis; Vincristine
PubMed: 33627139
DOI: 10.1186/s12957-021-02153-1 -
Clinical & Translational Oncology :... Jun 2021Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive...
PURPOSE
Considering the increased cancer patient survivorship, the focus is now on addressing the impacts of treatment on quality of life. In young people, altered reproductive function is a major issue and its effects in young males are largely neglected by novel research. To improve clinician awareness, we systematically reviewed side effects of chemotherapy for Hodgkin lymphoma (HL) in young males.
METHODS
The review was prospectively registered (PROSPERO N. CRD42019122868). Three databases (Medline via PUBMED, SCOPUS, and Cochrane Library) were searched for studies featuring males aged 13-51-years who underwent chemotherapy for HL using ABVD (Adriamycin® (doxorubicin), bleomycin, vinblastine, and dacarbazine) or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) regimens. These chemotherapy regimens were compared against each other using sperm characteristics, FSH, and inhibin B levels to measure fertility levels.
RESULTS
Data were extracted from five studies featuring 1344 patients. 6 months post-ABVD saw marked deterioration in sperm count, further reduced by more cycles (P = 0.05). Patients treated with BEACOPP rather than ABVD were more prone to oligospermia. Receiving fewer cycles of both regimens increased the likelihood of sperm production recovering. Patients treated with 6-8 cycles of BEACOPP did not recover spermiogenesis.
CONCLUSIONS
ABVD and BEACOPP regimens significantly reduce fertility function to varying effects depending on treatment duration. ABVD temporarily causes significant reductions in male fertility, whereas BEACOPP's effects are more permanent. Therefore, clinicians should discuss fertility preservation with male patients receiving infertility-inducing gonadotoxic therapy. Further high-quality studies are required to more adequality describe the risk to fertility by chemotherapy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Dacarbazine; Doxorubicin; Etoposide; Fertility; Hodgkin Disease; Humans; Infertility, Male; Male; Prednisone; Procarbazine; Vinblastine; Vincristine
PubMed: 32944834
DOI: 10.1007/s12094-020-02483-8