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Journal of Surgical Oncology Mar 2014Isolated limb infusion (ILI) was developed as a simplified and minimally invasive alternative to isolated limb perfusion (ILP) to treat unresectable limb melanoma. A... (Review)
Review
Isolated limb infusion (ILI) was developed as a simplified and minimally invasive alternative to isolated limb perfusion (ILP) to treat unresectable limb melanoma. A number of centers around the world have reported their results using this procedure. In this study a systematic review of reported ILI experiences was undertaken. A literature search was conducted according to the guidelines for systematic reviews in order to select eligible papers reporting limb toxicity and response rates following ILI using melphalan and actinomycin D to treat limb melanoma. A total of 576 patients from seven publications were included. Regional toxicity following ILI was low: no visible effect of the treatment or slight erythema or edema was observed in 79% of the patients, while considerable erythema and/or edema with blistering was experienced by 19%. In 2% there was a threatened or actual compartment syndrome. No procedure-related amputation was reported. Complete response occurred in 33% of the patients and partial response in 40%, an overall response rate of 73%. Stable disease and progressive disease were achieved in 14% and 13% of the patients, respectively. This first systematic review of ILI procedures using melphalan and actinomycin D indicates that regional toxicity was generally low, with satisfactory response rates. When comparing ILI and ILP, it must be borne in mind that ILI is often performed in significantly older patients and in patients with higher stages of disease, which decreases the likelihood of a favorable response.
Topics: Antibiotics, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Dactinomycin; Humans; Melanoma; Melphalan; Neoplasm Metastasis
PubMed: 24522939
DOI: 10.1002/jso.23553 -
Cancer Nursing 2014The central nervous system is a unique sanctuary site for malignant disease. To ensure optimal disease control, intrathecal (IT) chemotherapy is commonly given in... (Review)
Review
BACKGROUND
The central nervous system is a unique sanctuary site for malignant disease. To ensure optimal disease control, intrathecal (IT) chemotherapy is commonly given in conjunction with standard chemotherapy protocols, thus providing the opportunity for medication errors.
OBJECTIVE
A systematic review of the current literature on medication errors associated with the administration of IT chemotherapy was conducted.
METHODS
English-language literature published from January 1960 through June 2013 was accessed. Case reports, clinical studies, and review articles pertaining to IT medication errors were included in the review. References of all relevant articles were searched for additional citations.
RESULTS
Twenty-two cases of accidental IT overdoses have been reported with methotrexate and 1 with cytarabine. There have been numerous cases of antineoplastic agents intended for administration by the parenteral route being inadvertently given intrathecally. Vincristine has been implicated 31 times (25 deaths), as well as vindesine, asparaginase, bortezomib, daunorubicin, and dactinomycin. This has led to profound toxicity and, commonly, death. Unfortunately, many cases go unrecognized or unreported.
CONCLUSIONS
The best method for eliminating the risk of IT medication errors is to develop effective methods of prevention and incorporate them into oncology and hematology practice internationally. Strategies include abolishing the syringe as a method of vinca alkaloid administration and substituting small-volume intravenous bags, and developing novel methods for intraspinal drug administration.
IMPLICATIONS FOR PRACTICE
The nursing profession is in a unique position to influence change and lead the way in establishing preventative strategies into current practice.
Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cytarabine; Evidence-Based Medicine; Humans; Injections, Spinal; Medication Errors; Methotrexate; Vincristine
PubMed: 24201315
DOI: 10.1097/NCC.0000000000000108 -
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... Dec 2012Gestational 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.
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: 23235667
DOI: 10.1002/14651858.CD008891.pub2 -
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 -
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... Apr 2009Gestational trophoblastic disease (GTD) includes gestational trophoblastic tumour and hydatidiform mole. Many women of reproductive age are affected by this disease... (Review)
Review
BACKGROUND
Gestational trophoblastic disease (GTD) includes gestational trophoblastic tumour and hydatidiform mole. Many women of reproductive age are affected by this disease although its incidence differs by geographical location. A number of chemotherapy regimens are used for treating the disease, such as methotrexate, actinomycin D and cyclophosphamide (MAC), methotrexate, actinomycin D, cyclophosphamide, doxorubicin, melphalan, hydroxyurea and vincristine (CHAMOC), etoposide, methotrexate and actinomycin (EMA) plus cyclophosphamide and vincristine (CO) (EMA-CO), etoposide, methotrexate and actinomycin (EMA) plus etoposide and cisplatin(EP) (EMA-EP). The efficacy of these drugs has not been systematically reviewed.
OBJECTIVES
To determine the efficacy and safety of combination chemotherapy in treating high-risk GTT.
SEARCH STRATEGY
Electronic searches of Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2008), MEDLINE, EMB and CBM, May 2008. Four journals were handsearched and other searching methods were used for identifying more studies.
SELECTION CRITERIA
The review included randomised controlled trials (RCTs) or quasi-RCTs of combination chemotherapy for treating high-risk GTT. Patients with placental-site trophoblastic tumour (PSTT), who had received chemotherapy in the previous two weeks, or patients with chemotherapy intolerance were excluded.
DATA COLLECTION AND ANALYSIS
Two investigators independently collected data using a data extraction form. Meta-analysis was not performed and the review was conducted as a narrative review.
MAIN RESULTS
One study with 42 participants was included in this review. It indicated that a MAC regimen was better than a CHAMOCA regimen for high-risk GTT because of lower toxicity. The quality of the study was unclear.
AUTHORS' CONCLUSIONS
The methodological limitations of the included study prevent any firm conclusions about the best combination chemotherapy regimen for high-risk GTT. High quality studies are required.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Doxorubicin; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Hydroxyurea; Melphalan; Methotrexate; Pregnancy; Trophoblastic Tumor, Placental Site; Vincristine
PubMed: 19370618
DOI: 10.1002/14651858.CD005196.pub3 -
The Cochrane Database of Systematic... Jan 2009Gestational trophoblastic neoplasia (GTN) is a rare but curable disease. The incidence in Europe and North America is nearly 1.5 per 1000 live births but much higher... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gestational trophoblastic neoplasia (GTN) is a rare but curable disease. The incidence in Europe and North America is nearly 1.5 per 1000 live births but much higher rates are reported from Africa and Asia. The majority of the patients respond to evacuation of the uterus plus or minus chemotherapy, however, occasional patients will die. Patients are categorised into low or high risk groups using a variety of scoring systems. A large number of regimens are used worldwide in the management of low risk GTN; there are reports of 14 different regimens in the English literature. The choice of the regimen is usually dependent on geographic location, prior training and current experience with the specific regimen. Regimens have significant differences in the route of administration, hospitalisation and side effects and so have a bearing on healthcare cost. Patients are therefore exposed to different regimens with the potential for different response rates and different side effect profiles.
OBJECTIVES
To determine the efficacy and safety of first line chemotherapy in the treatment of low risk GTN.
SEARCH STRATEGY
We electronically searched Cochrane Gynaecological Cancer Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3 2008), MEDLINE and EMBASE in September 2008. We performed additional searching of online trial registers and conference proceedings. We cross examined article references to identify relevant papers not detected by the electronic search.
SELECTION CRITERIA
The review included randomised controlled trials (RCTs) , quasi-RCTs and non-RCTs (cohort and case control studies (CCS)) for the treatment of low risk GTN.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion in the review using a data extraction form. Meta-analysis was performed by pooling the relative risk (RR) of individual trials.
MAIN RESULTS
Eight studies met the review entry criteria (n = 769). There were four RCTs and four CCS. Six different treatment regimens were identified; weekly methotrexate, 5-day methotrexate, 8-day methotrexate-folinic acid, "pulsed" dactinomycin, 5-day dactinomycin and the combination of methotrexate and dactinomycin. "Pulsed" dactinomycin was superior to weekly methotrexate in achieving primary cure without significantly increasing toxicity (three studies, RR 3.00, 95% CI 1.10 to 8.17, n = 392) . Eight-day methotrexate-folinic acid did not show significant advantage over 5-day methotrexate both in reducing toxicity or primary cure rate (two studies, RR 1.07, 95% CI 0.91 to 1.25, n = 169). The combination of methotrexate-dactinomycin resulted in significantly increased toxicity without significantly improving primary cure rate.
AUTHORS' CONCLUSIONS
Based on the available evidence from the included RCTs, the authors conclude that "pulsed" dactinomycin is superior to weekly parenteral methotrexate at the reported dosages. However, the authors believe that rigorously designed, multicentred, randomised double-blind trials are required to evaluate other combinations of chemotherapy regimens, most importantly "pulsed" dactinomycin with the widely used 8-day methotrexate-folinic acid.
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: 19160319
DOI: 10.1002/14651858.CD007102.pub2 -
The Cochrane Database of Systematic... Jul 2006Gestational trophoblastic disease (GTD) includes gestational trophoblastic tumour and hydatidiform mole. Many women of reproductive age are affected by this disease... (Review)
Review
BACKGROUND
Gestational trophoblastic disease (GTD) includes gestational trophoblastic tumour and hydatidiform mole. Many women of reproductive age are affected by this disease although its incidence differs by geographical location. A number of chemotherapy regimens are used for treating the disease, such as methotrexate, actinomycin D and cyclophosphamide (MAC), methotrexate, actinomycin D, cyclophosphamide, doxorubicin, melphalan, hydroxyurea and vincristine (CHAMOC), etoposide, methotrexate and actinomycin (EMA) plus cyclophosphamide and vincristine (CO) (EMA-CO), etoposide, methotrexate and actinomycin (EMA) plus etoposide and cisplatin(EP) (EMA-EP). The efficacy of these drugs has not been systematically reviewed.
OBJECTIVES
To determine the efficacy and safety of combination chemotherapy in treating high-risk GTT.
SEARCH STRATEGY
Electronic searches of MEDLINE, EMB, Cochrane Central Register of Controlled Trials (CENTRAL) and CBM were carried out. Four journals were handsearched and other searching methods were used for identifying more studies.
SELECTION CRITERIA
The review included randomized controlled trials (RCTs) or quasi-RCTs of combination chemotherapy for treating high-risk GTT. Patients with placental-site trophoblastic tumour (PSTT), who had received chemotherapy in the previous two weeks, or patients with chemotherapy intolerance were excluded.
DATA COLLECTION AND ANALYSIS
Two investigators independently collected data using a data extraction form. Meta-analysis was not performed and the review was conducted as a narrative review.
MAIN RESULTS
One study with 42 participants was included in this review. It indicated that a MAC regimen was better than a CHAMOCA regimen for high-risk GTT because of lower toxicity. The quality of the study was unclear.
AUTHORS' CONCLUSIONS
The methodological limitations of the included study prevent any firm conclusions about the best combination chemotherapy regimen for high-risk GTT. High quality studies are required.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Doxorubicin; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Hydroxyurea; Leucovorin; Methotrexate; Pregnancy; Trophoblastic Tumor, Placental Site; Vincristine
PubMed: 16856085
DOI: 10.1002/14651858.CD005196.pub2 -
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