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BJOG : An International Journal of... Apr 2023High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
High-risk gestational trophoblastic neoplasia (GTN) is rare and treated with diverse approaches. Limited published institutional data has yet to be systematically reviewed.
OBJECTIVES
To compile global high-risk GTN (prognostic score ≥7) cohorts to summarise treatments and outcomes by disease characteristics and primary chemotherapy.
SEARCH STRATEGY
MEDLINE, Embase, Scopus, ClinicalTrials.gov and Cochrane were searched through March 2021.
SELECTION CRITERIA
Full-text manuscripts reporting mortality among ≥10 high-risk GTN patients.
DATA COLLECTION AND ANALYSIS
Binomial proportions were summed, and random-effects meta-analyses performed.
MAIN RESULTS
From 1137 records, we included 35 studies, representing 20 countries. Among 2276 unique high-risk GTN patients, 99.7% received chemotherapy, 35.8% surgery and 4.9% radiation. Mortality was 10.9% (243/2236; meta-analysis: 10%, 95% confidence interval [CI] 7-12%) and likelihood of complete response to primary chemotherapy was 79.7% (1506/1890; meta-analysis: 78%, 95% CI: 74-83%). Across 24 reporting studies, modern preferred chemotherapy (EMA/CO or EMA/EP) was associated with lower mortality (overall: 8.8 versus 9.5%; comparative meta-analysis: 8.1 versus 12.4%, OR 0.42, 95% CI: 0.20-0.90%, 14 studies) and higher likelihood of complete response (overall: 76.6 versus 72.8%; comparative meta-analysis: 75.9 versus 60.7%, OR 2.98, 95% CI: 1.06-8.35%, 14 studies), though studies focused on non-preferred regimens reported comparable outcomes. Mortality was increased for ultra-high-risk disease (30 versus 7.5% high-risk; meta-analysis OR 7.44, 95% CI: 4.29-12.9%) and disease following term delivery (20.8 versus 7.3% following molar pregnancy; meta-analysis OR 2.64, 95% CI: 1.10-6.31%). Relapse rate estimates ranged from 3 to 6%.
CONCLUSIONS
High-risk GTN is responsive to several chemotherapy regimens, with EMA/CO or EMA/EP associated with improved outcomes. Mortality is increased in patients with ultra-high-risk, relapsed and post-term pregnancy disease.
Topics: Pregnancy; Female; Humans; Methotrexate; Dactinomycin; Neoplasm Recurrence, Local; Gestational Trophoblastic Disease; Hydatidiform Mole; Retrospective Studies
PubMed: 36648416
DOI: 10.1111/1471-0528.17374 -
The Cochrane Database of Systematic... Jan 2016Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will... (Review)
Review
BACKGROUND
Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic.
OBJECTIVES
To determine which chemotherapy regimen/s for the treatment of resistant or relapsed GTN is/are the most effective and the least toxic.
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4), MEDLINE and EMBASE up to October 2011. In addition, we handsearched the relevant society conference proceedings and study reference lists. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to 16 Novemeber 2015. In addition, we searched online clinical trial registries for ongoing trials.
SELECTION CRITERIA
Only randomised controlled trials (RCTs) were included.
DATA COLLECTION AND ANALYSIS
We designed a data extraction form and planned to use random-effects methods in Review Manager 5.1 for meta-analyses.
MAIN RESULTS
The search identified no RCTs; therefore we were unable to perform any meta-analyses.
AUTHORS' CONCLUSIONS
RCTs in GTN are scarce owing to the low prevalence of this disease and its highly chemosensitive nature. As chemotherapeutic agents may be associated with substantial side effects, the ideal treatment should achieve maximum efficacy with minimal side effects. For methotrexate-resistant or recurrent low-risk GTN, a common practice is to use sequential five-day dactinomycin, followed by MAC (methotrexate, dactinomycin, cyclophosphamide) or EMA/CO (etoposide, methotrexate, dactinomycin, cyclophosphamide, vinblastine) if further salvage therapy is required. However, five-day dactinomycin is associated with more side effects than pulsed dactinomycin, therefore an RCT comparing the relative efficacy and safety of these two regimens in the context of failed primary methotrexate treatment is desirable.For high-risk GTN, EMA/CO is the most commonly used first-line therapy, with platinum-etoposide combinations, particularly EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin), being favoured as salvage therapy. Alternatives, including TP/TE (paclitaxel, cisplatin/ paclitaxel, etoposide), BEP (bleomycin, etoposide, cisplatin), FAEV (floxuridine, dactinomycin, etoposide, vincristine) and FA (5-fluorouracil (5-FU), dactinomycin), may be as effective as EMA/EP and associated with fewer side effects; however, this is not clear from the available evidence and needs testing in well-designed RCTs. In the UK, an RCT comparing interventions for resistant/recurrent GTN will be very challenging owing to the small numbers of patients with this scenario. International multicentre collaboration is therefore needed to provide the high-quality evidence required to determine which salvage regimen/s have the best effectiveness-to-toxicity ratio in low- and high-risk disease. Future research should include economic evaluations and long-term surveillance for secondary neoplasms.
Topics: Drug Resistance, Neoplasm; Female; Gestational Trophoblastic Disease; Humans; Neoplasm Recurrence, Local; Pregnancy
PubMed: 26760424
DOI: 10.1002/14651858.CD008891.pub3 -
The Cochrane Database of Systematic... Jul 2012This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear.
OBJECTIVES
To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN.
SEARCH METHODS
In September 2008, we electronically searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2008), MEDLINE and EMBASE. In addition, we searched online trial registers, conference proceedings and reference lists of identified studies. We re-ran these searches in February 2012 for this updated review.
SELECTION CRITERIA
For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated version of the review, we included only RCTs.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed by pooling the risk ratio (RR) of individual trials.
MAIN RESULTS
We included five moderate to high quality RCTs (517 women) in the updated review. These studies all compared methotrexate with dactinomycin. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) dactinomycin (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV dactinomycin (75 women) and one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV dactinomycin (49 women).Overall, dactinomycin was associated with significantly higher rates of primary cure than methotrexate (five studies, 513 women; RR 0.64, 95% Confidence Interval (CI) 0.54 to 0.76). Methotrexate was associated with significantly more treatment failure than dactinomycin (five studies, 513 women; RR 3.81, 95% CI 1.64 to 8.86). We consider this evidence to be of a moderate quality.There was no significant difference between the two groups with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too heterogeneous to be conclusive. No severe adverse effects (SAEs) occurred in either group in three out of the five included studies and there was no significant difference in SAEs between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I² = 60%), however, there was a trend towards fewer SAEs in the methotrexate group. We considered this evidence to be of a low quality due to substantial heterogeneity and low consistency in the occurrence/reporting of SAEs between trials.
AUTHORS' CONCLUSIONS
Dactinomycin is more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, compared with methotrexate. There is limited evidence relating to side-effects, however, the pulsed dactinomycin regimen does not appear to be associated with significantly more side-effects than the low-dose methotrexate regimen and therefore should compare favourably to the five- and eight-day methotrexate regimens in this regard.We consider pulsed dactinomycin to have a better cure rate than, and a side-effect profile at least equivalent to, methotrexate when used for first-line treatment of low-risk GTN. Data from a large ongoing trial of pulsed dactinomycin compared with five- and eight-day methotrexate regimens is likely to have an important impact on our confidence in these findings.
Topics: Antineoplastic Agents; Case-Control Studies; Cohort Studies; Dactinomycin; Drug Administration Schedule; Female; Gestational Trophoblastic Disease; Humans; Leucovorin; Methotrexate; Pregnancy; Randomized Controlled Trials as Topic; Risk; Vitamin B Complex
PubMed: 22786502
DOI: 10.1002/14651858.CD007102.pub3 -
The Cochrane Database of Systematic... Jun 2016This is the second update of a Cochrane review that was first published in 2009, Issue 1, . Gestational trophoblastic neoplasia (GTN) is a rare but curable disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is the second update of a Cochrane review that was first published in 2009, Issue 1, . Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear.
OBJECTIVES
To determine the efficacy and safety of first-line chemotherapy in the treatment of low-risk GTN.
SEARCH METHODS
We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase in September 2008, February 2012, and January 2016. In addition, we searched online trial registers for protocols and ongoing trials.
SELECTION CRITERIA
For the original review, we included randomised controlled trials (RCTs), quasi-RCTs and non-RCTs that compared first-line chemotherapy for the treatment of low-risk GTN. For this updated versions of the review, we included only RCTs.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion and extracted data to a pre-designed data extraction form. Meta-analysis was performed using the random-effects model.
MAIN RESULTS
We included seven RCTs (667 women) in this updated review. Most studies were at a low or moderate risk of bias and all compared methotrexate with actinomycin D. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) actinomycin D (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV actinomycin D (75 women), one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV actinomycin D (49 women), and one study compared eight-day IM MTX-FA with bi-weekly pulsed IV actinomycin D. One study contributed no data. Moderate-certainty evidence indicates that actinomycin D is probably more likely to lead to primary cure than methotrexate (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.57 to 0.75; six trials, 577 participants; I(2) = 26%), and first-line methotrexate treatment is probably more likely to fail than actinomycin D treatment (RR 3.55, 95% CI 1.81 to 6.95; six trials, 577 participants; I(2) = 61%; moderate-certainty evidence) Low-certainty evidence suggests that there may be little or no difference between methotrexate and actinomycin D treatment with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too inconsistent to be conclusive. Low-certainty evidence suggests that there may be little or no difference in the risk of severe adverse events (SAEs) between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I² = 60%); however, the direction of effect favours methotrexate and more evidence is needed. Furthermore, evidence from subgroup analyses suggests that actinomycin D may be associated with a greater risk of SAEs than methotrexate (low-certainty evidence). We found no evidence on the effect of these treatments on future fertility.
AUTHORS' CONCLUSIONS
Actinomycin D is probably more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, than a methotrexate regimen. There may be little or no difference between the pulsed actinomycin D regimen and the methotrexate regimen with regard to side-effects. However, actinomycin D may be associated with a greater risk of severe adverse events (SAEs) than a methotrexate regimen. Higher-certainty evidence is still needed on treating low-risk GTN and the four ongoing trials are likely to make a significant contribution to this field. Given the variety of treatment regimens, findings from these trials could facilitate a network meta-analysis in the next version of this review to help women and clinicians determine the best treatment options for low-risk GTN.
Topics: Antineoplastic Agents; Case-Control Studies; Cohort Studies; Dactinomycin; Drug Administration Schedule; Female; Gestational Trophoblastic Disease; Humans; Leucovorin; Methotrexate; Pregnancy; Randomized Controlled Trials as Topic; Risk; Vitamin B Complex
PubMed: 27281496
DOI: 10.1002/14651858.CD007102.pub4 -
The Cochrane Database of Systematic... 2001Between 10% and 35% of women with operable breast cancer will experience an isolated locoregional recurrence following their primary treatment. There is currently no... (Review)
Review
BACKGROUND
Between 10% and 35% of women with operable breast cancer will experience an isolated locoregional recurrence following their primary treatment. There is currently no good evidence that adjuvant systemic treatment is effective in this situation and there is no standard treatment for women who have such a recurrence.
OBJECTIVES
To investigate whether additional systemic treatment will improve the result of local therapy in regard to relapse-free and overall survival in women with potentially curatively resected loco-regional recurrence following breast cancer, who have not had a previous or synchronous distant metastases.
SEARCH STRATEGY
Searches were done, in the first half of 2001, of the specialised register of the Cochrane Breast Cancer Collaborative Review Group, The Cochrane Library, MEDLINE and EMBASE. In addition, the records of the Early Breast Cancer Trialists' Collaborative Group were checked for any relevant trials. The citations in articles reviewing the treatment of locoregional recurrence of breast cancer were checked.
SELECTION CRITERIA
Randomised controlled trials or trials in which women were allocated to treatment or observation by a quasi-random process (such as alternation or date of birth) were eligible. Our aim was to consider separately women with a first incidence of isolated loco-regional recurrence in the treated breast, the chest wall or the regional lymphnode areas (except clavicular nodes) which can be resected without (R0) or with (R1) microscopically demonstrable residual disease. Women with previous or synchronous distant metastases were to be excluded from this part of the review. The second part of the review was to consider women with inoperable loco-regional recurrence and / or clavicular lymphnode involvement, regardless of previous or synchronous metastases.
DATA COLLECTION AND ANALYSIS
We identified three closed studies in which there were a total of four randomised comparisons of systemic therapy versus observation for women who have received radiotherapy for loco-regional recurrence of breast cancer. One trial assessed Actinomyicin-D and randomised 32 patients in the 1960s and another randomised the same number of women to alpha-interferon versus observation in the early 1980s. The Swiss SAKK trial assessed tamoxifen for "good risk" patients and combination chemotherapy (Vincristine, Doxorubicin and Cyclophosphamide) for "poor risk" patients. It randomised 178 and 50 women respectively during 1982-1991. Where possible, data on relapse-free and overall survival were extracted for these trials and analysed using RevMan 4.1. No attempt was made to pool the results of the studies because of clinical heterogeneity and the small number of randomised patients. Three ongoing trials of chemotherapy versus observation have been identified.
MAIN RESULTS
The trial of 32 women who received either radiotherapy alone or in combination with systemic administration of Actinomycin-D found that chemotherapy improved the local control rate but had no apparent effect on overall survival. The interferon trial, which also included a total of only 32 patients, showed that the addition of alpha-Interferon to local treatment of locoregional recurrent breast cancer had no apparent effect on the further course of the disease. The Swiss SAKK trial of tamoxifen (178 women randomized) found an improvement in disease-free survival but not in overall survival and no results are available for the 50 women randomized into the concurrent trial of chemotherapy. The three ongoing trials of chemotherapy have a total target accrual of nearly 2000 patients.
REVIEWER'S CONCLUSIONS
This systematic review of randomised trials provides insufficient evidence to do other than conclude that the most appropriate form of practice for women with loco-regional recurrence of breast cancer is participation in randomised trials of systemic treatment versus observation.
Topics: Antineoplastic Agents; Breast Neoplasms; Combined Modality Therapy; Dactinomycin; Female; Humans; Interferon-alpha; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Tamoxifen
PubMed: 11687148
DOI: 10.1002/14651858.CD002195 -
The Cochrane Database of Systematic... Jan 2013This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are malignant disorders of the placenta that include invasive hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Choriocarcinoma and invasive hydatidiform mole respond well to chemotherapy: low-risk tumours are treated with single-agent chemotherapy (e.g. methotrexate or actinomycin D), whereas high-risk tumours are treated with combination chemotherapy (e.g. EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine)). Various drug combinations may be used for high-risk tumours; however, the comparative efficacy and safety of these regimens is not clear.
OBJECTIVES
To determine the efficacy and safety of combination chemotherapy in treating high-risk GTN.
SEARCH METHODS
For the original review, we searched the Cochrane Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2008), MEDLINE, EMBASE and CBM in May 2008. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to September 2012. In addition, we searched online clinical trial registries for ongoing trials.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs comparing first-line combination chemotherapy interventions in women with high-risk GTN.
DATA COLLECTION AND ANALYSIS
Two review authors independently collected data using a data extraction form. Meta-analysis could not be performed as we included only one study.
MAIN RESULTS
We included one RCT of 42 women with high-risk GTN who were randomised to MAC (methotrexate, actinomycin D and chlorambucil) or the modified CHAMOCA regimen (cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, doxorubicin, melphalan and vincristine). There were no statistically significant differences in efficacy of the two regimens; however women in the MAC group experienced statistically significantly less toxicity overall and less haematological toxicity than women in the CHAMOCA group. During the study period, six women in the CHAMOCA group died compared with one in the MAC group. This study was stopped early due to unacceptable levels of toxicity in the CHAMOCA group. We identified no RCTs comparing EMA/CO with MAC or other chemotherapy regimens.
AUTHORS' CONCLUSIONS
CHAMOCA is not recommended for GTN treatment as it is more toxic and not more effective than MAC. EMA/CO is currently the most widely used first-line combination chemotherapy for high-risk GTN, although this regimen has not been rigorously compared to other combinations such as MAC or FAV in RCTs. Other regimens may be associated with less acute toxicity than EMA/CO; however, proper evaluation of these combinations in high-quality RCTs that include long-term surveillance for secondary cancers is required. We acknowledge that, given the low incidence of GTN, RCTs in this field are difficult to conduct, hence multicentre collaboration is necessary.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Doxorubicin; Early Termination of Clinical Trials; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Hydroxyurea; Leucovorin; Melphalan; Methotrexate; Pregnancy; Trophoblastic Tumor, Placental Site; Vincristine
PubMed: 23440800
DOI: 10.1002/14651858.CD005196.pub4 -
The Cochrane Database of Systematic... Sep 2017This is an update of the original Cochrane Review published in Cochrane Library, Issue 10, 2012.Hydatidiform mole (HM), also called a molar pregnancy, is characterised... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the original Cochrane Review published in Cochrane Library, Issue 10, 2012.Hydatidiform mole (HM), also called a molar pregnancy, is characterised by an overgrowth of foetal chorionic tissue within the uterus. HMs may be partial (PM) or complete (CM) depending on their gross appearance, histopathology and karyotype. PMs usually have a triploid karyotype, derived from maternal and paternal origins, whereas CMs are diploid and have paternal origins only. Most women with HM can be cured by evacuation of retained products of conception (ERPC) and their fertility preserved. However, in some women the growth persists and develops into gestational trophoblastic neoplasia (GTN), a malignant form of the disease that requires treatment with chemotherapy. CMs have a higher rate of malignant transformation than PMs. It may be possible to reduce the risk of GTN in women with HM by administering prophylactic chemotherapy (P-Chem). However, P-Chem given before or after evacuation of HM to prevent malignant sequelae remains controversial, as the risks and benefits of this practice are unclear.
OBJECTIVES
To evaluate the effectiveness and safety of P-Chem to prevent GTN in women with a molar pregnancy. To investigate whether any subgroup of women with HM may benefit more from P-Chem than others.
SEARCH METHODS
For the original review we performed electronic searches in the Cochrane Gynaecological Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2012), MEDLINE (1946 to February week 4, 2012) and Embase (1980 to 2012, week 9). We developed the search strategy using free text and MeSH. For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5, 2017), MEDLINE (February 2012 to June week 1, 2017) and Embase (February 2012 to 2017, week 23). We also handsearched reference lists of relevant literature to identify additional studies and searched trial registries.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of P-Chem for HM.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion in the review and extracted data using a specifically designed data collection form. Meta-analyses were performed by pooling data from individual trials using Review Manager 5 (RevMan 5) software in line with standard methodological procedures expected by Cochrane methodology.
MAIN RESULTS
The searches identified 161 records; after de-duplication and title and abstract screening 90 full-text articles were retrieved. From these we included three RCTs with a combined total of 613 participants. One study compared prophylactic dactinomycin to no prophylaxis (60 participants); the other two studies compared prophylactic methotrexate to no prophylaxis (420 and 133 participants). All participants were diagnosed with CMs. We considered the latter two studies to be of poor methodological quality.P-Chem reduced the risk of GTN occurring in women following a CM (3 studies, 550 participants; risk ratio (RR) 0.37, 95% confidence interval (CI) 0.24 to 0.57; I² = 0%; P < 0.00001; low-quality evidence). However, owing to the poor quality (high risk of bias) of two of the included studies, we performed sensitivity analyses excluding these two studies. This left only one small study of high-risk women to contribute data for this primary outcome (59 participants; RR 0.28, 95% CI 0.10 to 0.73; P = 0.01); therefore we consider this evidence to be of low quality.The time to diagnosis was longer in the P-Chem group than the control group (2 studies, 33 participants; mean difference (MD) 28.72, 95% CI 13.19 to 44.24; P = 0.0003; low-quality evidence); and the P-Chem group required more courses to cure subsequent GTN (1 poor-quality study, 14 participants; MD 1.10, 95% CI 0.52 to 1.68; P = 0.0002; very low quality evidence).There were insufficient data to perform meta-analyses for toxicity, overall survival, drug resistance and reproductive outcomes.
AUTHORS' CONCLUSIONS
P-Chem may reduce the risk of progression to GTN in women with CMs who are at a high risk of malignant transformation; however, current evidence in favour of P-Chem is limited by the poor methodological quality and small size of the included studies. As P-Chem may increase drug resistance, delays treatment of GTN and may expose women toxic side effects, this practice cannot currently be recommended.
Topics: Antineoplastic Agents; Dactinomycin; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Incidence; Methotrexate; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 28892119
DOI: 10.1002/14651858.CD007289.pub3 -
The Cochrane Database of Systematic... Oct 2012Hydatidiform mole (HM), also called a molar pregnancy, is characterised by an overgrowth of foetal chorionic tissue within the uterus. HMs may be partial (PM) or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hydatidiform mole (HM), also called a molar pregnancy, is characterised by an overgrowth of foetal chorionic tissue within the uterus. HMs may be partial (PM) or complete (CM) depending on their gross appearance, histopathology and karyotype. PMs usually have a triploid karyotype, derived from maternal and paternal origins, whereas CMs are diploid and have paternal origins only. Most women with HM can be cured by evacuation of retained products of conception (ERPC) and their fertility preserved. However, in some women the growth persists and develops into gestational trophoblastic neoplasia (GTN), a malignant form of the disease that requires treatment with chemotherapy. CMs have a higher rate of malignant transformation than PMs. It may be possible to reduce the risk of GTN in women with HM by administering prophylactic chemotherapy (P-Chem). However, P-Chem given before or after evacuation of HM to prevent malignant sequelae remains controversial, as the risks and benefits of this practice are unclear.
OBJECTIVES
To systematically review the evidence for the effectiveness and safety of P-Chem to prevent GTN in women with a molar pregnancy.
SEARCH METHODS
We performed electronic searches in the Cochrane Gynaecological Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2012), MEDLINE (1946 to February week 4, 2012) and EMBASE (1980 to week 9, 2012). The search strategy was developed using free text and medical subject headings (MESH). We handsearched reference lists of relevant literature to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of P-Chem for HM.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion in the review and extracted data using a specifically designed data collection form. Meta-analyses were performed by pooling data from individual trials using RevMan 5.1 software.
MAIN RESULTS
We included three RCTs with a combined total of 613 participants. One study compared prophylactic dactinomycin to no prophylaxis (60 participants); the other two studies compared prophylactic methotrexate to no prophylaxis (420 and 133 participants). All participants were diagnosed with CMs. We considered the latter two studies to be of poor methodological quality.P-Chem reduced the risk of GTN occurring in women following a CM (3 studies, 550 participants; RR 0.37; 95% confidence interval (CI) 0.24 to 0.57; I(2) = 0%; P < 0.00001), However, owing to the poor quality of two of the included studies, we performed sensitivity analyses excluding these two studies. This left only one small study of high-risk women to contribute data for this primary outcome (59 participants; RR 0.28; 95% CI 0.10 to 0.73; P = 0.01), therefore we consider this evidence to be of a low quality.The time to diagnosis was longer in the P-Chem group than the control group (2 studies, 33 participants; mean difference (MD) 28.72; 95% CI 13.19 to 44.24; P = 0.0003) and the P-Chem group required more courses to cure subsequent GTN (1 poor-quality study, 14 participants; MD 1.10; 95% CI 0.52 to 1.68; P = 0.0002). We consider this evidence to be of a low to very low quality for similar reasons to those listed above.There were insufficient data to perform meta-analyses for toxicity, overall survival, drug resistance and reproductive outcomes.
AUTHORS' CONCLUSIONS
P-Chem may reduce the risk of progression to GTN in women with CMs who are at a high risk of malignant transformation; however, current evidence in favour of P-Chem is limited by the poor methodological quality and small size of the included studies. As P-Chem may increase drug resistance, delay treatment of GTN and expose women unnecessarily to toxic side effects, this practice cannot currently be recommended.
Topics: Antineoplastic Agents; Dactinomycin; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Methotrexate; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 23076934
DOI: 10.1002/14651858.CD007289.pub2 -
BMC Cancer Oct 2021Actinomycin-D (Act-D) and Methotrexate (MTX) are both effective first-line agents for low-risk gestational trophoblastic neoplasia (LRGTN) with no consensus regarding... (Comparative Study)
Comparative Study Meta-Analysis
Direct comparisons of efficacy and safety between actinomycin-D and methotrexate in women with low-risk gestational trophoblastic neoplasia: a meta-analysis of randomized and high-quality non-randomized studies.
BACKGROUND
Actinomycin-D (Act-D) and Methotrexate (MTX) are both effective first-line agents for low-risk gestational trophoblastic neoplasia (LRGTN) with no consensus regarding which is more effective or less toxic. The primary objective of this meta-analysis is to compare Act-D with MTX in the treatment of LRGTN.
METHODS
We systematically searched electronic databases, conferences abstracts and trial registries for randomized controlled trials (RCTs) and high-quality non-randamized controlled trials (non-RCTs), comparing Act-D with MTX for patients with LRGTN. Studies were full-text screened for quality assessment and data extraction. Eligible studies must have reported complete remission rate. A fixed-effects meta-analysis was conducted to quantify the efficacy and safety of Act-D and MTX on odds ratios (ORs) and 95% confidence intervals (95%CIs), respectively.
RESULTS
A total of 8 RCTs and 9 non-RCTs (1674 patients) were included. In terms of efficacy, Act-D is superior to MTX in complete remission (80.2% [551/687] vs 65.1% [643/987]; OR 2.15, 95%CI 1.70 to 2.73). In the stratified analysis, patients from RCTs and non-RCTs both had a better complete remission from Act-D-based regimen (RCTs: 81.2% [259/319] vs 66.1% [199/301], OR 2.17, 95%CI 1.49 to 3.16; non-RCTs: 79.3% [292/368] vs 65.0% [444/686], OR 2.14, 95%CI 1.57 to 2.92). In terms of safety, patients receiving Act-D had higher risks of suffering nausea (OR 2.35, 95%CI 1.68 to 3.27), vomiting (OR 2.40, 95%CI 1.63 to 3.54), and alopecia (OR 2.76, 95%CI 1.60 to 4.75). Notably, liver toxicity (OR 0.38, 95%CI 0.19 to 0.76) was the only one that was conformed to have a higher risk for patients receiving MTX. In addition, the pooled results showed no significant difference of anaemia, leucocytopenia, neutropenia, thrombocytopnia, constipation, diarrhea, anorexia, and fatigue between Act-D and MTX.
CONCLUSIONS
Our meta-analysis suggests that Act-D had better efficacy profile in general, and MTX had less toxicities in LRGTN. Future clinical trials should be better orchestrated to provide more valid data on efficacy and toxicity.
Topics: Alopecia; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Chemical and Drug Induced Liver Injury; Dactinomycin; Female; Gestational Trophoblastic Disease; Humans; Methotrexate; Nausea; Pregnancy; Randomized Controlled Trials as Topic; Remission Induction; Risk; Treatment Outcome; Vomiting
PubMed: 34663255
DOI: 10.1186/s12885-021-08849-7 -
Taiwanese Journal of Obstetrics &... Jan 2019Placenta accreta is a potentially life-threatening condition that may complicate a first-trimester abortion in rare occasions, and it can be difficult to recognize. We...
Placenta accreta is a potentially life-threatening condition that may complicate a first-trimester abortion in rare occasions, and it can be difficult to recognize. We reviewed the literature in PubMed-indexed English journals through August 2018 for first-trimester postabortal placenta accreta, after which 19 articles and 23 case reports were included. The risk factors for the development of abnormal placentation are previous cesarean section (87%), previous history of uterine curettage (43.5%), and previous history of surgical evacuation of a retained placenta (4.3%). Ten patients (43.5%) had an advanced age (≧35 years). Most patients clinically presented with vaginal bleeding, ranging from intermittent or irregular bleeding, persistent bleeding, and profuse or massive bleeding. The onset of symptoms might be during the intra- or immediate postoperative period. Some patients had delayed symptoms 1 week to 2 years postoperatively. Conservative management may be attempted as the primary rescue, including uterine artery embolization (UAE), transcatheter arterial chemoembolization (TACE) with dactinomycin, and laparoscopic hysterotomy with placental tissue removal. However, most reports in the literature suggested either abdominal or laparoscopic hysterectomy as the definitive treatment for first-trimester postabortal placenta accreta. High index of clinical suspicion with anticipation of placenta accreta in early pregnancy is highly essential for timely diagnosis, providing the physician better opportunities to promptly manage this emergent condition and improve outcomes.
Topics: Abortion, Therapeutic; Female; Humans; Hysterectomy; Placenta Accreta; Postoperative Period; Pregnancy; Pregnancy Trimester, First; Risk Factors; Ultrasonography, Prenatal; Uterine Hemorrhage
PubMed: 30638461
DOI: 10.1016/j.tjog.2018.11.032