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Health Technology Assessment... Mar 2006To examine the clinical effectiveness and cost-effectiveness of intravenous formulations of topotecan monotherapy, pegylated liposomal doxorubicin hydorocholoride (PLDH)... (Review)
Review
Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation.
OBJECTIVES
To examine the clinical effectiveness and cost-effectiveness of intravenous formulations of topotecan monotherapy, pegylated liposomal doxorubicin hydorocholoride (PLDH) monotherapy and paclitaxel used alone or in combination with a platinum-based compound for the second-line or subsequent treatment of advanced ovarian cancer.
DATA SOURCES
Electronic databases covering publication years 2000-4. Company submissions.
REVIEW METHODS
Seventeen databases were searched for randomised controlled trials (RCTs) and systematic reviews for the clinical effectiveness of PLDH, topotecan and paclitaxel and economic evaluations of the cost-effectiveness of PLDH, topotecan and paclitaxel. Selected studies were quality assessed and data extracted, as were the three company submissions. A new model was developed to assess the costs of the alternative treatments, the differential mean survival duration and the impact of health-related quality of life. Monte-Carlo simulation was used to reflect uncertainty in the cost-effectiveness results.
RESULTS
Nine RCTs were identified. In five of these trials, both the comparators were used within their licensed indications. Of these five, three included participants with both platinum-resistant and platinum-sensitive advanced ovarian cancer, and a further two only included participants with platinum-sensitive disease. The comparators that were assessed in the three trials that included both subtypes of participants were PLDH versus topotecan, topotecan versus paclitaxel and PLDH versus paclitaxel. In the further two trials that included participants with the subtype of platinum-sensitive disease, the comparators that were assessed were single-agent paclitaxel versus a combination of cyclophosphamide, doxorubicin and cisplatin (CAP) and paclitaxel plus platinum-based chemotherapy versus conventional platinum-based therapy alone. A further four trials were identified and included in the review in which one of the comparators in the trial was used outside its licensed indication. The comparators assessed in these trials were oxaliplatin versus paclitaxel, paclitaxel given weekly versus every 3 weeks, paclitaxel at two different dose levels and oral versus intravenous topotecan. Four studies met the inclusion criteria for the cost-effectiveness review. The review of the economic evidence from the literature and industry submissions identified a number of significant limitations in existing studies assessing the cost-effectiveness of PLDH, topotecan and paclitaxel. Analysis 1 assessed the cost-effectiveness of PLDH, topotecan and paclitaxel administered as monotherapies. Sensitivity analysis was undertaken to explore the impact of patient heterogeneity (e.g. platinum-sensitive and platinum-resistant/refractory patients), the inclusion of additional trial data and alternative assumptions regarding treatment and monitoring costs. In the base-case results for Analysis 1, paclitaxel monotherapy emerged as the cheapest treatment. When the incremental cost-effectiveness ratios (ICERs) were estimated, topotecan was dominated by PLDH. Hence the options considered in the estimation of the ICERs were paclitaxel and PLDH. The ICER for PLDH compared with paclitaxel was pound 7033 per quality-adjusted life-year (QALY) in the overall patient population (comprising platinum-sensitive, -refractory and -resistant patients). The ICER was more favourable in the platinum-sensitive group ( pound 5777 per QALY) and less favourable in the platinum-refractory/resistant group ( pound 9555 per QALY). The cost-effectiveness results for the base-case analysis were sensitive to the inclusion of additional trial data. Incorporating the results of the additional trial data resulted in less favourable estimates for the ICER for PLDH versus paclitaxel compared with the base-case results. The ICER of PLDH compared with paclitaxel was pound 20,620 per QALY in the overall patient population, pound 16,183 per QALY in the platinum-sensitive population and pound 26,867 per QALY in the platinum-resistant and -refractory population. The results from Analysis 2 explored the cost-effectiveness of the full range of treatment comparators for platinum-sensitive patients. The treatment options considered in this model comprised PLDH, topotecan, paclitaxel-monotherapy, CAP, paclitaxel/platinum combination therapy and platinum monotherapy. Owing to the less robust approaches that were employed to synthesise the available evidence and the heterogeneity between the different trials, the reliability of these results should be interpreted with some caution. Topotecan, paclitaxel monotherapy and PLDH were all dominated by platinum monotherapy (i.e. higher costs and lower QALYs). After excluding these alternatives, the treatments that remained under consideration were platinum monotherapy, CAP and paclitaxel-platinum combination therapy. Of these three alternatives, platinum monotherapy was the least costly and least effective. The ICER for CAP compared with platinum monotherapy was pound 16,421 per QALY. The ICER for paclitaxel-platinum combination therapy compared with CAP was pound 20,950 per QALY.
CONCLUSIONS
For participants with platinum-resistant disease there was a low probability of response to treatment with PLDH, topotecan or paclitaxel. Furthermore, there was little difference between the three comparators in relation to overall survival. The comparators did, however, differ considerably in their toxicity profiles. Given the low survival times and response rates, it appears that the maintenance of quality of life and the control of symptoms and toxicity are paramount in this patient group. As the three comparators differed significantly in terms of their toxicity profiles, patient and physician choice is also an important element that should be addressed when decisions are made regarding second-line therapy. It can also be suggested that this group of patients may benefit from being included in further clinical trials of new drugs. For participants with platinum-sensitive disease there was a considerable range of median survival times observed across the trials. The most favourable survival times and response rates were observed for paclitaxel and platinum combination therapy. This suggests that treatment with combination therapy may be more beneficial than treatment with a single-agent chemotherapeutic regimen. In terms of single-agent compounds, the evidence suggests that PLDH is more effective than topotecan. Evidence from a further trial that compared PLDH and paclitaxel suggests that there is no significant difference between these two comparators in this trial. The three comparators did, however, differ significantly in terms of their toxicity profiles across the trials. Although treatment with PLDH may therefore be more beneficial than that with topotecan, patient and physician choice as to the potential toxicities associated with each of the comparators and the patient's ability and willingness to tolerate these are of importance. Assuming the NHS is willing to pay up to pound 20,000-40,000 per additional QALY, PLDH appears to be cost-effective compared with topotecan and paclitaxel monotherapy, in terms of the overall patient population and the main subgroups considered. The cost-effectiveness results for the base-case analysis were sensitive to the inclusion of additional trial data. Incorporating the results of additional trial data gave less favourable estimates for the ICER for PLDH versus paclitaxel monotherapy, compared with the base-case results. Although the ICER of PLDH compared with paclitaxel monotherapy was less favourable, PLDH was still cost-effective compared with topotecan and paclitaxel monotherapy. For platinum-sensitive patients, the combination of paclitaxel and platinum appears to be cost-effective. On the strength of the evidence reviewed here, it can be suggested that participants with platinum-resistant disease may benefit from being included in further clinical trials of new drugs. To assess the effectiveness of combination therapy against a single-agent non-platinum-based compound, it can be suggested that a trial that compared paclitaxel in combination with a platinum-based therapy versus single-agent PLDH would be a reasonable option.
Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Cost-Benefit Analysis; Doxorubicin; Female; Humans; Liposomes; Ovarian Neoplasms; Paclitaxel; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Survival Analysis; Topotecan
PubMed: 16545208
DOI: 10.3310/hta10090 -
Cardiology in Review 2018Doxorubicin is an important cause of chemotherapy-induced cardiomyopathy. Prior studies have found conflicting results of whether nonstrain diastolic parameters can... (Meta-Analysis)
Meta-Analysis Review
Doxorubicin is an important cause of chemotherapy-induced cardiomyopathy. Prior studies have found conflicting results of whether nonstrain diastolic parameters can predict doxorubicin-induced cardiotoxicity. We performed a systematic review of English written publications using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The following inclusion criteria were applied: cancer subjects, echo-derived nonstrain diastolic profile, and patients compared before and after treatment to predict systolic dysfunction. The following exclusion criteria were applied: other cardiotoxic agents, non-echo studies, or used protective medications. Meta-analysis was performed using comprehensive meta-analysis software V3 to calculate cumulative means, SD, and odds ratios (ORs). Only 4 studies were designed to predict doxorubicin-induced cardiotoxicity. Of the 7 common parameters identified among studies, only 4 were significant: mitral E [OR: 3.4; 95% confidence interval (CI): 1.5-7.8; P = 0.003]; lateral E' (OR: 3.7; 95% CI: 1.5-9.4; P < 0.005); mitral E/A (OR: 4.3; 95% CI: 2.1-8.9; P < 0.0001); and lateral S' (OR: 2.7; 95% CI: 1.2-5.8; P = 0.01). We found that conventional nonstrain diastolic parameters predicted doxorubicin-induced systolic dysfunction. Whether nonstrain diastolic parameters can be used to supplement strain imaging for predicting doxorubicin-induced systolic function warrants further investigation in larger studies.
Topics: Antibiotics, Antineoplastic; Cardiomyopathies; Diastole; Doxorubicin; Echocardiography; Heart Ventricles; Humans; Neoplasms; Prognosis; Stroke Volume
PubMed: 29045286
DOI: 10.1097/CRD.0000000000000161 -
The Lancet. Haematology Apr 2020Patients treated for non-Hodgkin lymphoma are at risk of cardiovascular adverse events, with the risk of heart failure being particularly high. A regimen of... (Meta-Analysis)
Meta-Analysis
Cardiovascular adverse events in patients with non-Hodgkin lymphoma treated with first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP): a systematic review and meta-analysis.
BACKGROUND
Patients treated for non-Hodgkin lymphoma are at risk of cardiovascular adverse events, with the risk of heart failure being particularly high. A regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone, with (R-CHOP) or without (CHOP) rituximab is the standard first-line treatment for aggressive non-Hodgkin lymphoma, and doxorubicin and cyclophosphamide are both associated with left ventricular dysfunction. The aim of this systematic review and meta-analysis was to evaluate the cardiovascular toxicity of this regimen.
METHODS
We systematically searched PubMed, EMBASE, and the Cochrane Library from database inception to June 3, 2019, for clinical trials and observational studies in adult patients with non-Hodgkin lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, and non-Hodgkin lymphoma not otherwise specified) that received first-line treatment with R-CHOP or CHOP. Studies reporting on cardiovascular adverse events and treatment-related cardiovascular mortality were included. Abstracts and articles not written in English were excluded. The main outcomes were the proportion of patients with grade 3-4 cardiovascular adverse events and heart failure. Meta-analyses of one-sample proportions were done in all patients receiving CHOP or R-CHOP. Subgroup analyses on summary estimates were done to determine the effect of number of CHOP or R-CHOP cycles, cycle interval, age, and sex.
FINDINGS
Of 2314 identified entries, 137 studies (21 211 patients) published between April, 1984, and June, 2019 were eligible (9541 patients treated with CHOP, 11 293 patients treated with R-CHOP, 377 both regimens used in the study; median follow-up 39·0 months [IQR 25·5-52·8]). From the included studies, 85 subgroups were treated with CHOP, 76 with R-CHOP, and in four studies both CHOP and R-CHOP were used without a subdivision in separate groups. The pooled proportion for grade 3-4 cardiovascular adverse events, based on 77 studies (n=14 351 patients), was 2·35% (95% CI 1·81-2·93; heterogeneity test Q=326·21; τ=0·0042; I=71·40%; p<0·0001). For heart failure, the pooled proportion, based on 38 studies (n=5936 patients), was 4·62% (2·25-7·65; heterogeneity test Q=527·33; τ=0·0384; I=95·05%; p<0·0001), with a significant increase in reported heart failure from 1·64% (95% CI 0·82-2·65) to 11·72% (3·00-24·53) when cardiac function was evaluated post-chemotherapy (p=0·017). 53 (39%) of 137 studies were rated as having high risk of bias for incomplete outcome data and 54 (39%) for selective reporting.
INTERPRETATION
The considerable increase of reported heart failures with cardiac monitoring, indicates that this complication often remains undiagnosed in patients with non-Hodgkin lymphoma who received first-line R-CHOP or CHOP. Our findings are of importance to raise awareness of this complication among clinicians treating patients with non-Hodgkin lymphoma and stresses the need for cardiac monitoring during and after chemotherapy. Prompt initiation of treatment for heart failure in the presymptomatic phase can mitigate the progression to more advanced heart failure stages.
FUNDING
None.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Diseases; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Non-Hodgkin; Prednisone; Rituximab; Severity of Illness Index; Vincristine
PubMed: 32135128
DOI: 10.1016/S2352-3026(20)30031-4 -
BMC Cancer Jan 2024The use of taxanes following the first trimester of pregnancy is endorsed by current clinical guidelines. However, evidence regarding their safety in terms of obstetric...
BACKGROUND
The use of taxanes following the first trimester of pregnancy is endorsed by current clinical guidelines. However, evidence regarding their safety in terms of obstetric and neonatal outcomes is limited.
METHODS
A comprehensive literature search was performed using the MEDLINE, CENTRAL and Web of Sciences databases from their inception up to 12/16/2022. Eligibility criteria included gestational taxane use, presentation of original findings, and individual case data presented. A descriptive statistical analysis was undertaken.
RESULTS
A total of 159 patients treated with taxane-containing regimens during pregnancy were identified, resulting in 162 fetuses exposed in utero. The majority of patients had breast cancer (n = 88; 55.3%) or cervical cancer (n = 45; 28.3%). The most commonly employed taxane was paclitaxel (n = 131; 82.4%). A total of 111 (69.8%) patients were also treated with other cytotoxic drugs during pregnancy, including platinum salts (n = 70; 63.0%) and doxorubicin/cyclophosphamide (n = 20; 18.0%). While most patients received taxanes during the second trimester of pregnancy (n = 79; 70.0%), two were exposed to taxanes in the first trimester. Obstetric outcomes were reported in 105 (66.0%) cases, with the most frequent adverse events being preterm contractions or premature rupture of membranes (n = 12; 11.4%), pre-eclampsia/HELLP syndrome (n = 6; 5.7%), and oligohydramnios/anhydramnios (n = 6; 5.7%). All cases with pregnancy outcome available resulted in live births (n = 132). Overall, 72 (54.5%) neonates were delivered preterm, 40 (30.3%) were classified as small for gestational age (SGA), and 2 (1.5%) had an Apgar score of < 7 at 5 min. Perinatal complications included acute respiratory distress syndrome (n = 14; 10.6%), hyperbilirubinemia (n = 5; 3.8%), and hypoglycemia (n = 2; 1.5%). In addition, 7 (5.3%) cases of congenital malformations were reported. At a median follow-up of 16 months, offspring health status was available for 86 (65.2%), of which 13 (15.1%) had a documented complication, including delayed speech development, recurrent otitis media, and acute myeloid leukemia.
CONCLUSIONS
Taxanes appear to be safe following the first trimester of pregnancy, with obstetric and fetal outcomes being similar to those observed in the general obstetric population. Future studies should aim to determine the most effective taxane regimen and dosage for use during gestation, with a specific focus on treatment safety.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Taxoids; Paclitaxel; Pregnancy Outcome; Bridged-Ring Compounds; Oligohydramnios
PubMed: 38166767
DOI: 10.1186/s12885-023-11704-6 -
Cancers Jul 2021MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to... (Review)
Review
MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to establish the incidence of double expressor status in patients with de novo DLBCL and identify the predictive value of this biomarker on treatment response through systematic review and meta-analysis. PubMed and Embase were searched for studies published through December 2019 that reported proportions of double expressor DLBCL. The pooled proportions of MYC and BCL2 expression, both alone and in combination, were computed using the inverse variance method for calculating weights and by the DerSimonian-Laird method. The pooled odds ratios (ORs) of complete remission (CR) rate were calculated, and meta-regression analysis was conducted to explore heterogeneity. Forty-one studies (7054 patients) were included. The pooled incidence of double expressor status in DLBCL was 23% (95% confidence interval [CI], 20-26%), with an adjusted estimate of 31% (95% CI, 27-36%). Neither MYC/BCL2 protein cutoff values, race, mean, or median age of included patients, or overall study quality was a significant factor of heterogeneity ( ≥ 0.20). Cases without double expressor status demonstrated a higher probability of CR to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment (OR, 2.69; 95% CI, 1.55-4.67). Our results reaffirm the predictive power of this important biomarker.
PubMed: 34282799
DOI: 10.3390/cancers13133369 -
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 -
Journal of the American Heart... Sep 2021Background Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to... (Meta-Analysis)
Meta-Analysis
Background Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin-induced cardiotoxicity and to evaluate mechanisms underlying exercise-mediated cardioprotection using (pre)clinical evidence. Methods and Results We conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Cochrane's and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tools were used to assess the validity of human and animal studies, respectively. Cardiotoxicity outcomes reported by ≥3 studies were pooled and structured around the type of exercise intervention. Forty articles were included, of which 3 were clinical studies. Overall, in humans (sample sizes ranging from 24 to 61), results were indicative of exercise-mediated cardioprotection, yet they were not sufficient to establish whether physical exercise protects against doxorubicin-induced cardiotoxicity. In animal studies (n=37), a pooled analysis demonstrated that forced exercise interventions significantly mitigated in vivo and ex vivo doxorubicin-induced cardiotoxicity compared with nonexercised controls. Similar yet slightly smaller effects were found for voluntary exercise interventions. We identified oxidative stress and related pathways, and less doxorubicin accumulation as mechanisms underlying exercise-induced cardioprotection, of which the latter could act as an overarching mechanism. Conclusions Animal studies indicate that various exercise interventions can protect against doxorubicin-induced cardiotoxicity in rodents. Less doxorubicin accumulation in cardiac tissue could be a key underlying mechanism. Given the preclinical evidence and limited availability of clinical data, larger and methodologically rigorous clinical studies are needed to clarify the role of physical exercise in preventing cardiotoxicity in patients with cancer. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42019118218.
Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Doxorubicin; Exercise; Humans
PubMed: 34472371
DOI: 10.1161/JAHA.121.021580 -
Breast Cancer Research and Treatment Nov 2017To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human... (Meta-Analysis)
Meta-Analysis Review
Systematic review and network meta-analysis comparing palbociclib with chemotherapy agents for the treatment of postmenopausal women with HR-positive and HER2-negative advanced/metastatic breast cancer.
PURPOSE
To compare palbociclib + letrozole and palbociclib + fulvestrant with chemotherapy agents in postmenopausal women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (ABC/MBC) who had no prior systemic treatment for advanced disease (first line) or whose disease progressed after prior endocrine therapy or chemotherapy (second line).
METHODS
A systematic search identified randomized controlled trials (RCTs) published from January 2000 to January 2016 that compared endocrine-based therapies, chemotherapy agents, and/or chemotherapy agents + biological therapies in the first- and second-line treatment of postmenopausal women with HR+/HER2- ABC/MBC. The main outcome of interest was progression-free survival (PFS)/time to progression (TTP). Bayesian network meta-analyses (NMAs) and pairwise meta-analyses were conducted. Heterogeneity and inconsistency were assessed.
RESULTS
Sixty RCTs met eligibility criteria and were stratified by line of therapy. In the first line, palbociclib + letrozole showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (95% CrI 0.11-0.72)] and mitoxantrone [HR 0.28 (0.13-0.61)], and trended toward improvements versus paclitaxel [HR 0.59 (0.19-1.96)], docetaxel [HR 0.51 (0.14-2.03)] and other monotherapy or combination agents (HRs ranging from 0.24 to 0.99). In the second line, palbociclib + fulvestrant showed statistically significant improvements in PFS/TTP versus capecitabine [intermittent: HR 0.28 (0.13-0.65)], mitoxantrone [HR 0.26 (0.12-0.53)], and pegylated liposomal doxorubicin [HR 0.19 (0.07-0.50)], and trended toward improvements versus paclitaxel [HR 0.48 (0.16-1.44)], docetaxel [HR 0.71 (0.24-2.13)] and other monotherapy or combination agents (HRs ranging from 0.23-0.89). NMA findings aligned with direct evidence and were robust to sensitivity analyses.
CONCLUSIONS
Palbociclib + letrozole and palbociclib + fulvestrant demonstrate trends in incremental efficacy compared with chemotherapy agents for the first- and second-line treatment of HR +/HER2- ABC/MBC.
Topics: Age Factors; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Female; Humans; Neoplasm Metastasis; Neoplasm Staging; Piperazines; Postmenopause; Pyridines; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retreatment; Survival Analysis; Treatment Outcome
PubMed: 28752187
DOI: 10.1007/s10549-017-4404-4 -
Revista Da Associacao Medica Brasileira... 2013This study aimed to establish the safety of chemotherapy use in pregnant women with breast cancer, and to find possible effects in the fetus. A search of MEDLINE/PubMed,... (Review)
Review
This study aimed to establish the safety of chemotherapy use in pregnant women with breast cancer, and to find possible effects in the fetus. A search of MEDLINE/PubMed, LILACS, SciELO, Cochrane, UpToDate, and Google Scholar databases was performed to identify publications, 86 articles published from 2001 to 2012 were retrieved and evaluated by two readers in accordance predetermined exclusion and inclusion criteria; 39 articles were selected. All the chemotherapy drugs used to treat breast cancer during pregnancy belonged to class D, and consisted of 5-fluorouracil (F), doxorubicin (A) or epirubicin (E) and cyclophosphamide (C), or the combination doxorubicin and cyclophosphamide (AC), a safe regimen when used after the first trimester of pregnancy. Few studies evaluated the use of taxanes (T), such as docetaxel (D) and paclitaxel (P), with no increase in the occurrence of fetal defects and other maternal complications when used in the second and third trimesters of pregnancy. The use of trastuzumab in pregnant women is associated with oligohydramnios and anhydramnios; thus, it is not recommended during pregnancy. As almost all studies were observational and retrospective, new prospective studies on the subject are needed.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Evidence-Based Medicine; Female; Humans; Pregnancy; Pregnancy Complications, Neoplastic
PubMed: 23582560
DOI: 10.1016/j.ramb.2012.10.003 -
Cancer Treatment Reviews Feb 2018Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy remains poorly defined.
METHODS
We conducted a systematic review and meta-analysis to evaluate benefits and harms of multi-agent chemotherapy in advanced STS. Eligible studies were randomized trials of chemotherapy in advanced STS comparing single agent to multi-agent therapy. Data from studies reporting a hazard ratio (HR) and 95% confidence intervals (CI) for OS and progression-free survival (PFS) were pooled in a meta-analysis. Meta-regression was utilized to explore the association between efficacy (OS and PFS) and both toxicity and dose intensity.
RESULTS
We identified 22 trials published between 1974 and April 2016 and comprising 5044 patients. Overall, multi-agent chemotherapy was associated with improved OS (HR:0.79, p = 0.02), and borderline improvement in PFS (HR:0.86, p = 0.05). While the effect on OS was similar in trials with non-anthracycline controls compared to those with anthracycline controls (HR for OS 0.73 vs. 0.82, p for difference = 0.63) there was a non-significantly greater effect for multi-agent chemotherapy on PFS in non-anthracycline RCT (HR for PFS 0.73 vs. 0.91, p for difference = 0.13). Compared to studies with cytotoxic therapy-based multi-agent therapy, a non-significantly greater magnitude of effect among studies with biological/cytostatic experimental groups was seen (HR for OS 0.64 vs. 0.86, p for difference = 0.37). There was a borderline significant association between dose reductions (which were more common in combination arms) and worse PFS (beta = 0.70, p = 0.053).
CONCLUSION
Multi-agent chemotherapy is associated with a modest, but statistically significant improvement in outcomes in STS. Combining chemotherapy with non-cytotoxic agents might represent a promising strategy.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Doxorubicin; Humans; Randomized Controlled Trials as Topic; Sarcoma
PubMed: 29253836
DOI: 10.1016/j.ctrv.2017.12.003