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The Cochrane Database of Systematic... May 2014Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective.
OBJECTIVES
To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV).
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer.
DATA COLLECTION AND ANALYSIS
Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software.
MAIN RESULTS
We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data.Overall survival (OS) and progression-free survival (PFS) was longer with adjuvant chemotherapy compared with adjuvant radiotherapy (OS: hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.57 to 0.99, I² = 22%; and PFS: HR 0.74, 95% CI 0.59 to 0.92, I² = 0%). Sensitivity analysis using adjusted and unadjusted OS data, gave similar results. In subgroup analyses, the effects on survival in favour of chemotherapy were not different for stage III and IV, or stage IIIA and IIIC (tests for subgroup differences were not significant and I² = 0%). This evidence was of moderate quality. Data from one trial showed that women receiving adjuvant chemotherapy were more likely to experience haematological and neurological adverse events and alopecia, and more likely to discontinue treatment (33/194 versus 6/202; RR 5.73, 95% CI 2.45 to 13.36), than those receiving adjuvant radiotherapy. There was no statistically significant difference in treatment-related deaths between the chemotherapy and radiotherapy treatment arms (8/309 versus 5/311; Risk Ratio (RR) 1.67, 95% CI 0.55 to 5.00).There was no clear difference in PFS between intervention groups in the one trial that compared CDP versus CD (552 women; HR 0.90, 95% CI 0.69 to 1.17). We considered this evidence to be of moderate quality. Mature OS data from this trial were not yet available. Severe haematological and neurological adverse events occurred more frequently with CDP than CD.We found no trials to include of adjuvant chemotherapy versus chemoradiation in advanced endometrial cancer; however we identified one ongoing trial of this comparison.
AUTHORS' CONCLUSIONS
There is moderate quality evidence that chemotherapy increases survival time after primary surgery by approximately 25% relative to radiotherapy in stage III and IV endometrial cancer. There is limited evidence that it is associated with more adverse effects. There is some uncertainty as to whether triplet regimens offer similar survival benefits over doublet regimens in the long-term. Further research is needed to determine which chemotherapy regimen(s) are the most effective and least toxic, and whether the addition of radiotherapy further improves outcomes. A large trial evaluating the benefits and risks of adjuvant chemoradiation versus chemotherapy in advanced endometrial cancer is ongoing.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Doxorubicin; Endometrial Neoplasms; Female; Humans; Neoplasm Staging; Paclitaxel; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic
PubMed: 24832785
DOI: 10.1002/14651858.CD010681.pub2 -
The Cochrane Database of Systematic... Mar 2016This review update has been managed by both the Childhood Cancer and Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Groups.The use of anthracycline... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review update has been managed by both the Childhood Cancer and Cochrane Gynaecological, Neuro-oncology and Orphan Cancer Groups.The use of anthracycline chemotherapy is limited by the occurrence of cardiotoxicity. To prevent this cardiotoxicity, different anthracycline dosage schedules have been studied.
OBJECTIVES
To determine the occurrence of cardiotoxicity with the use of different anthracycline dosage schedules (that is peak doses and infusion durations) in people with cancer.
SEARCH METHODS
We searched the databases of the Cochrane Register of Controlled Trials (CENTRAL) (the Cochrane Library, Issue 11, 2015), MEDLINE (1966 to December 2015), and EMBASE (1980 to December 2015). We also searched reference lists of relevant articles, conference proceedings, experts in the field, and ongoing trials databases.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in which different anthracycline dosage schedules were compared in people with cancer (children and adults).
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection, the 'Risk of bias' assessment, and data extraction. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
We identified 11 studies: 7 evaluated different infusion durations (803 participants), and 4 evaluated different peak doses (5280 participants). Seven studies were RCTs addressing different anthracycline infusion durations; we identified long-term follow-up data for one of the trials in this update. The meta-analysis showed a statistically significant lower rate of clinical heart failure with an infusion duration of six hours or longer as compared to a shorter infusion duration (risk ratio (RR) 0.27; 95% confidence interval 0.09 to 0.81; 5 studies; 557 participants). The majority of participants included in these studies were adults with different solid tumours. For different anthracycline peak doses, we identified two RCTs addressing a doxorubicin peak dose of less than 60 mg/m(2) versus 60 mg/m(2) or more, one RCT addressing a liposomal doxorubicin peak dose of 25 mg/m(2) versus 50 mg/m(2), and one RCT addressing an epirubicin peak dose of 83 mg/m(2) versus 110 mg/m(2). A significant difference in the occurrence of clinical heart failure was identified in none of the studies. The participants included in these studies were adults with different solid tumours. High or unclear 'Risk of bias' issues were present in all studies.
AUTHORS' CONCLUSIONS
An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure, and it seems to reduce the risk of subclinical cardiac damage. Since there is only a small amount of data for children and data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children.We identified no significant difference in the occurrence of clinical heart failure in participants treated with a doxorubicin peak dose of less than 60 mg/m(2) or 60 mg/m(2) or more. Only one RCT was available for the other identified peak doses, so we can make no definitive conclusions about the occurrence of cardiotoxicity. More high-quality research is needed, both in children and adults and in leukaemias and solid tumours.
Topics: Adult; Anthracyclines; Antibiotics, Antineoplastic; Cardiac Output, Low; Child; Heart; Heart Diseases; Humans; Neoplasms; Randomized Controlled Trials as Topic
PubMed: 26938118
DOI: 10.1002/14651858.CD005008.pub4 -
The Cochrane Database of Systematic... Aug 2014Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of highly active antiretroviral therapy (HAART), there has been a decline in its incidence.However, Kaposi's sarcoma continues to be diagnosed in HIV-infected patients.
OBJECTIVES
To assess the added advantage of chemotherapy plus HAART compared to HAART alone; and the advantages of different chemotherapy regimens in HAART and HAART naive HIV infected adults with severe or progressive Kaposi's sarcoma.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and , GATEWAY, the WHO Clinical Trials Registry Platform and the US National Institutes of Health's ClinicalTrials.gov for ongoing trials and the Aegis archive of HIV/AIDS for conference abstracts. An updated search was conducted in July 2014.
SELECTION CRITERIA
Randomised trials and observational studies evaluating the effects of any chemotherapeutic regimen in combination with HAART compared to HAART alone, chemotherapy versus HAART, and comparisons between different chemotherapy regimens.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the studies independently and extracted outcome data.We used the risk ratio (RR) with a 95% confidence interval (CI) as the measure of effect.We did not conduct meta-analysis as none of the included trials assessed identical chemotherapy regimens.
MAIN RESULTS
We included six randomised trials and three observational studies involving 792 HIV-infected adults with severe Kaposi's sarcoma.Seven studies included patients with a mix of mild to moderate (T0) and severe (T1) Kaposi's sarcoma. However, this review was restricted to the subset of participants with severe Kaposi's sarcoma disease.Studies comparing HAART plus chemotherapy to HAART alone showed the following: one trial comparing HAART plus doxorubicin,bleomycin and vincristine (ABV) to HAART alone showed a significant reduction in disease progression in the HAART plus ABV group (RR 0.10; 95% CI 0.01 to 0.75, 100 participants); there was no statistically significant reduction in mortality and no difference in adverse events. A cohort study comparing liposomal anthracyclines plus HAART to HAART alone showed a non-statistically significant reduction in Kaposi's sarcoma immune reconstitution inflammatory syndrome in patients that received HAART plus liposomal anthracyclines (RR 0.49; 95% CI 0.16 to 1.55, 129 participants).Studies comparing HAART plus chemotherapy to HAART plus a different chemotherapy regimen showed the following: one trial involving 49 participants and comparing paclitaxel versus pegylated liposomal doxorubicin in patients on HAART showed no difference in disease progression. Another trial involving 46 patients and comparing pegylated liposomal doxorubicin versus liposomal daunorubicin showed no participants with progressive Kaposi's sarcoma disease in either group.Studies comparing different chemotherapy regimens in patients from the pre-HAART era showed the following: in the single RCT comparing liposomal daunorubicin to ABV, there was no significant difference with the use of liposomal daunorubicin compared to ABV in disease progression (RR 0.78; 95% CI 0.34 to 1.82, 227 participants) and overall response rate. Another trial involving 178 participants and comparing oral etoposide versus ABV demonstrated no difference in mortality in either group. A non-randomised trial comparing bleomycin alone to ABV demonstrated a higher median survival time in the ABV group; there was also a non-statistically significant reduction in adverse events and disease progression in the ABV group (RR 11; 95% CI 0.67 to 179.29, 24 participants).An additional non-randomised study showed a non-statistically significant overall mortality benefit from liposomal doxorubicin as compared to conservative management consisting of either bleomycin plus vinblastine, vincristine or single-agent antiretroviral therapy alone (RR 0.93; 95% CI 0.75 to 1.15, 29 participants). The overall quality of evidence can be described as moderate quality. The quality of evidence was downgraded due to the small size of many of the included studies and small number of events.
AUTHORS' CONCLUSIONS
The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, when choosing from different chemotherapy regimens, there was no observed difference between liposomal doxorubicin, liposomal daunorubicin and paclitaxel.
Topics: Alitretinoin; Antineoplastic Agents; Antiretroviral Therapy, Highly Active; Bleomycin; Doxorubicin; Drug Therapy, Combination; Etoposide; HIV Infections; Humans; Liposomes; Observational Studies as Topic; Randomized Controlled Trials as Topic; Sarcoma, Kaposi; Skin Neoplasms; Tretinoin; Vincristine
PubMed: 25221796
DOI: 10.1002/14651858.CD003256.pub2 -
BMC Cancer May 2015The benefits associated with some cancer treatments do not come without risk. A serious side effect of some common cancer treatments is cardiotoxicity. Increased... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The benefits associated with some cancer treatments do not come without risk. A serious side effect of some common cancer treatments is cardiotoxicity. Increased recognition of the public health implications of cancer treatment-induced cardiotoxicity has resulted in a proliferation of systematic reviews in this field to guide practice. Quality appraisal of these reviews is likely to limit the influence of biased conclusions from systematic reviews that have used poor methodology related to clinical decision-making. The aim of this meta-review is to appraise and synthesise evidence from only high quality systematic reviews focused on the prevention, detection or management of cancer treatment-induced cardiotoxicity.
METHODS
Using Cochrane methodology, we searched databases, citations and hand-searched bibliographies. Two reviewers independently appraised reviews and extracted findings. A total of 18 high quality systematic reviews were subsequently analysed, 67 % (n = 12) of these comprised meta-analyses.
RESULTS
One systematic review concluded that there is insufficient evidence regarding the utility of cardiac biomarkers for the detection of cardiotoxicity. The following strategies might reduce the risk of cardiotoxicity: 1) The concomitant administration of dexrazoxane with anthracylines; 2) The avoidance of anthracyclines where possible; 3) The continuous administration of anthracyclines (>6 h) rather than bolus dosing; and 4) The administration of anthracycline derivatives such as epirubicin or liposomal-encapsulated doxorubicin instead of doxorubicin. In terms of management, one review focused on medical interventions for treating anthracycline-induced cardiotoxicity during or after treatment of childhood cancer. Neither intervention (enalapril and phosphocreatine) was associated with statistically significant improvement in ejection fraction or mortality.
CONCLUSION
This review highlights the lack of high level evidence to guide clinical decision-making with respect to the detection and management of cancer treatment-associated cardiotoxicity. There is more evidence with respect to the prevention of this adverse effect of cancer treatment. This evidence, however, only applies to anthracycline-based chemotherapy in a predominantly adult population. There is no high-level evidence to guide clinical decision-making regarding the prevention, detection or management of radiation-induced cardiotoxicity.
Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Cardiotoxicity; Databases, Bibliographic; Disease Management; Humans; Neoplasms
PubMed: 25948399
DOI: 10.1186/s12885-015-1407-6 -
Nutrients Jun 2017Most chemotherapeutic drugs are known to cause nephrotoxicity. Therefore, new strategies have been considered to prevent chemotherapy-induced nephrotoxicity. It is of... (Review)
Review
BACKGROUND
Most chemotherapeutic drugs are known to cause nephrotoxicity. Therefore, new strategies have been considered to prevent chemotherapy-induced nephrotoxicity. It is of note that (NS), or its isolated compound Thymoquinone (TQ), has a potential role in combating chemotherapy-induced nephrotoxicity.
AIM
To analyze and report the outcome of experimental animal studies on the protective effects of NS/TQ on chemotherapy-associated kidney complications.
DESIGN
Standard systematic review and narrative synthesis.
DATA SOURCES
MEDLINE, EMBASE databases were searched for relevant articles published up to March 2017. Additionally, a manual search was performed. Criteria for a study's inclusion were: conducted in animals, systematic reviews and meta-analysis, containing data on nephroprotective effects of NS/TQ compared to a placebo or other substance. All strains and genders were included.
RESULTS
The database search yielded 71 studies, of which 12 (cisplatin-induced nephrotoxicity 8; methotrexate-induced nephrotoxicity 1; doxorubicin-induced nephrotoxicity 2; ifosfamide-induced nephrotoxicity 1) were included in this review.
CONCLUSIONS
Experimental animal studies showed the protective effect of NS, or TQ, on chemotherapy-induced nephrotoxicity. These effects are caused by decreasing lipid peroxidation and increasing activity of antioxidant enzymes in renal tissue of chemotherapy-treated animals.
Topics: Animals; Antineoplastic Agents; Benzoquinones; Kidney Diseases; Nigella sativa; Phytotherapy
PubMed: 28629150
DOI: 10.3390/nu9060625 -
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 -
European Review For Medical and... Mar 2020We reviewed studies comparing survival outcomes such as overall survival (OS), progression free survival (PFS), and toxicity profile between patients treated with... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of pegylated liposomal doxorubicin and paclitaxel plus carboplatin-based chemotherapy as first line treatment for patients with ovarian cancer: a systematic review and meta-analysis of randomized controlled trials.
We reviewed studies comparing survival outcomes such as overall survival (OS), progression free survival (PFS), and toxicity profile between patients treated with Pegylated Liposomal Doxorubicin (PLD) combination and those treated with paclitaxel combination for ovarian cancer. We conducted systematic searches in various databases including Medline, Cochrane Controlled Register of Trials (CENTRAL), ScienceDirect, and Google Scholar from inception until August 2019. We used the Cochrane risk of bias tool to assess the quality of published trials. We carried out a meta-analysis with random-effects model and reported pooled Hazard ratios (HR) or Risk ratios (RR) with 95% confidence intervals (CIs). In total, we analysed 7 studies including 3,676 participants. All the studies were randomized controlled trials, while majority of studies had low bias risks. We did not find significant evidence for any of these outcomes except progression free survival (favoured PLD combination therapy pooled HR=0.87; 95% CI: 0.77-0.98). Worst grade toxicities like allergy (pooled RR: 1.86; 95% CI: 1.06-3.24) and neurotoxicity (pooled RR: 5.59; 95% CI: 1.43-21.84) were significantly higher among patients receiving paclitaxel combination therapy when compared to patients receiving PLD combination therapy. To summarize, PLD combination therapy is non-inferior to paclitaxel combination therapy in the management of ovarian cancer with respect to survival outcomes and worst grade toxicity profile. However, clinical recommendations cannot be made, as the evidence is not conclusive or significant enough.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Doxorubicin; Female; Humans; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; Randomized Controlled Trials as Topic
PubMed: 32271409
DOI: 10.26355/eurrev_202003_20655 -
Chinese Medical Journal Feb 2015Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly prolonged event-free survival in first-line chemotherapy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly prolonged event-free survival in first-line chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL). But relapse and refractory DLBCL occur frequently. Although rituximab is effective, its role in salvage therapy after autologous transplant remains unclear. Maintenance therapy with rituximab in responding patients after first line chemotherapy may be a useful novel approach capable of eradicating minimal residual disease and to bring survival benefit. This systematic review and meta-analysis evaluated the effects of rituximab maintenance treatment and salvage therapy of patients with DLBCL.
METHODS
We performed a systematic review and meta-analysis of randomized controlled trials and compared rituximab maintenance or salvage therapy at relapse with observation. We searched the Cochrane Library, PubMed, EMBASE, conference proceedings, databases of ongoing trials, and references of published trials. Two reviewers independently assessed the quality of the trials and extracted data. Hazard ratios for time-to-event data were estimated and pooled.
RESULTS
Seven trials including 1470 DLBCL patients were included in this systematic review and meta-analysis. Patients treated with maintenance rituximab have better overall survival (OS) and event-free survival (EFS) than patients in the observation arm, but there was no statistical significance. Patients who received rituximab salvage therapy for relapse or refractory DLBCL have statistically significantly better OS [HR of death = 0.72, 95% CI (0.55-0.94), P = 0.02], progression-free survival (PFS) [HR = 0.61, 95% CI (0.52-0.72), P < 0.05], odds ratio (OR) [RR = 1.26, 95% CI (1.07-1.47), P = 0.004] than patients in the observation arm. The rate of infection-related adverse events was higher with rituximab treatment [RR = 1.37, 95% CI = (1.14 - 1.65) P =0.001].
CONCLUSIONS
After first-line chemotherapy, the two rituximab-combined treatment strategies, including maintenance and salvage therapies can bring survival benefit. But due to the few studies, the low methodological quality assessment and the low outcome evidence quality, it's not confirmed that the two strategies are better than normal chemotherapy regimens. More high-quality randomized controlled trials are still needed to provide reliable evidence. The higher rate of infections after rituximab therapy should be taken into consideration when making treatment decisions.
Topics: Antibodies, Monoclonal, Murine-Derived; Humans; Lymphoma, Large B-Cell, Diffuse; Rituximab
PubMed: 25635435
DOI: 10.4103/0366-6999.150111 -
Annals of Oncology : Official Journal... Mar 2007Cytotoxic chemotherapy has a limited place in the management of advanced or recurrent endometrial cancer. Commonly used agents include cisplatin and doxorubicin, but the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cytotoxic chemotherapy has a limited place in the management of advanced or recurrent endometrial cancer. Commonly used agents include cisplatin and doxorubicin, but the side-effect profile may be unacceptable for many patients. The feasibility of administration of combination chemotherapy is limited in many patients on account of significant co-morbidity. While early-stage endometrial adenocarcinoma is a common gynaecological cancer with a favourable prognosis, advanced or recurrent disease presents a difficult management problem. The platinum and anthracycline compounds have been widely used for many years, but their impact on progression-free survival (PFS) and overall survival (OS) is not clear. This systematic review aimed to evaluate both the benefits and adverse effects of cytotoxic chemotherapy in these women.
PATIENTS AND METHODS
We carried out systematic searches for randomised controlled trials (RCTs) comparing chemotherapy with another intervention. Data were extracted from trial reports or supplied by investigators. Where possible, hazard ratios (HRs) were calculated for OS and PFS and odds ratios (ORs) were calculated for acute toxicity. The impact of more versus less intensive chemotherapy on OS, PFS and acute toxicity was assessed in a meta-analysis.
RESULTS
Eleven eligible RCTs were identified that recruited 2288 patients. A meta-analysis of six of these trials found that PFS [HR = 0.80, 95% confidence interval (CI) 0.71-0.90; P = 0.004], but not OS (HR = 0.90, 95% CI 0.80-1.03; P = 0.12), was significantly improved when more intensive chemotherapy was compared with less intensive chemotherapy. OS was improved when doxorubicin, cisplatin and other drugs were compared with doxorubicin and cisplatin. Toxicity was generally higher with more chemotherapy. There was insufficient evidence to assess the effect of chemotherapy on symptom control or quality of life (QoL). Platinums, anthracyclines and taxanes were the most studied in phase II trials and combinations gave the best responses, but patient selection and pre-treatment was very variable.
CONCLUSIONS
More intense combination chemotherapy significantly improves the disease-free survival and the data indicate a modest improvement in OS. The addition of anthracyclines (e.g. doxorubicin) or the taxanes [e.g. paclitaxel (Taxol)] to cisplatin increases the response rate. More intensive regimens are associated with the gain in survival. However, grade 3 and 4 myelosuppression and gastrointestinal toxicity are also increased. Future developments are likely to exploit specific molecular characteristics of endometrial cancers, including their hormone dependence, growth factor target overexpression and PTEN loss. While no one drug or regimen offers a clear benefit for women with advanced endometrial cancer, platinum drugs, anthracyclines and paclitaxel seem the most promising agents. Future trials should address the impact of such agents on QoL and symptom control in addition to survival. Chemotherapy and endocrine therapy need to be compared directly in an RCT.
Topics: Antineoplastic Agents; Disease-Free Survival; Endometrial Neoplasms; Female; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis; Quality of Life; Treatment Outcome
PubMed: 17150999
DOI: 10.1093/annonc/mdl417 -
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