Quimioterapia profiláctica para la mola hidatidiforme para la prevención de la neoplasia trofoblástica gestacional
Información
- DOI:
- https://doi.org/10.1002/14651858.CD007289.pub3Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 11 septiembre 2017see what's new
- Tipo:
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- Intervention
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Cáncer ginecológico, neurooncología y otros cánceres
- Copyright:
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- Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cifras del artículo
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Autores
Contributions of authors
Jing Fu, Fan He: protocol development, methodological quality assessment, retrieval of papers, data extraction, data analysis and writing the review.
Lingxia Xie, Hengxi Chen: protocol development, methodological quality assessment, data extraction and revision of the review.
Fang Fang, Taixiang Wu, Lina Hu: protocol development, content expert and revision of the review.
Tess Lawrie: methodology, data extraction, data analysis and writing.
Sources of support
Internal sources
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West China Secondary Hospital, Sichuan University, China.
External sources
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This review received methodological and statistical support as part of the 10/4001/12 NIHR Cochrane Programme Grant Scheme ‐ Optimising care, diagnosis and treatment pathways to ensure cost effectiveness and best practice in gynaecological cancer: improving evidence for the NHS, UK.
Declarations of interest
None.
Acknowledgements
We would like to thank:
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Clare Jess, Gail Quinn, Jo Morrison and the staff of the Cochrane Gynaecological Cancer Review Group for their advice and administrative support throughout the review process;
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Library staff at the Royal United Hospital, Bath, UK, for their assistance with the sourcing of articles;
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Donald Goldstein for responding to reprint requests;
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Elza Uberti for providing copies of Uberti 2006 and Uberti 2009 and responding to e‐mailed queries;
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Andri Andrijono for responding to e‐mailed queries.
The review published in 2012 received methodological and statistical support as part of the 10/4001/12 NIHR Cochrane Programme Grant Scheme ‒ Optimising Care, Diagnosis and Treatment Pathways to Ensure Cost Effectiveness and Best Practice in Gynaecological Cancer: Improving Evidence for the NHS.
This update was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to the Cochrane Gynaecological, Neuro‐oncology and Orphan Cancer Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.
Version history
| Published | Title | Stage | Authors | Version |
| 2017 Sep 11 | Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia | Review | Qiuyi Wang, Jing Fu, Lina Hu, Fang Fang, Lingxia Xie, Hengxi Chen, Fan He, Taixiang Wu, Theresa A Lawrie | |
| 2012 Oct 17 | Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia | Review | Jing Fu, Fang Fang, Lingxia Xie, Hengxi Chen, Fan He, Taixiang Wu, Lina Hu, Theresa A Lawrie | |
| 2008 Jul 16 | Prophylactic chemotherapy for hydatidiform mole | Protocol | Jing Fu, Taixiang Wu, Lingxia Xie, Hu Lina | |
Differences between protocol and review
None.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
Medical Subject Headings Check Words
Female; Humans; Pregnancy;
PICO
Study flow diagram.
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study.
Comparison 1 Prophylactic chemotherapy versus no prophylactic chemotherapy, Outcome 1 Incidence of GTN (overall).
Comparison 1 Prophylactic chemotherapy versus no prophylactic chemotherapy, Outcome 2 Incidence of GTN (high‐risk HM only).
Comparison 1 Prophylactic chemotherapy versus no prophylactic chemotherapy, Outcome 3 Time to GTN diagnosis.
Comparison 1 Prophylactic chemotherapy versus no prophylactic chemotherapy, Outcome 4 Number of courses of chemotherapy to cure.
Comparison 1 Prophylactic chemotherapy versus no prophylactic chemotherapy, Outcome 5 Mortality rate.
| Prophylactic chemotherapy compared with no prophylactic chemotherapy for hydatidiform mole | ||||||
| Patient or population: women with a molar pregnancy Settings: inpatient Intervention: methotrexate or dactinomycin Comparison: placebo or no prophylaxis | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| No prophylaxis | P‐Chem | |||||
| Incidence of GTN (including low‐quality studies) | Mixed‐risk population | RR 0.37 (0.24 to 0.57) | 550 women | ⊕⊕⊝⊝ | The NNTB to prevent 1 woman developing GTN after evacuation of HM was 6 (95% CI 5 to 10). We downgraded this evidence because this meta‐analysis included 2 studies that we considered to be of poor methodological quality. | |
| 254 per 1000 | 94 per 1000 (61 to 145) | |||||
| High‐risk population | RR 0.29 (0.14 to 0.60) | 99 women (2 studies) | ⊕⊕⊝⊝ | The NNTB for women with high‐risk HM was 3 (95% CI 2 to 5). We downgraded this evidence because the meta‐analysis included 2 small studies, 1 of which was of a poor methodological quality. | ||
| 490 per 1000 | 142 per 1000 (69 to 294) | |||||
| Incidence of GTN (excluding low‐quality studies) | High‐risk population | RR 0.28 (0.10 to 0.73) | 59 women (1 study) | ⊕⊕⊝⊝ | The NNTB to prevent 1 woman developing GTN after evacuation of high‐risk HM was 3 (95% CI 2 to 20). We downgraded this evidence because only 1 small study (Limpongsanurak 2001) contributed data, giving an imprecise result. | |
| 500 per 1000 | 140 per 1000 (50 to 365) | |||||
| Time to GTN diagnosis (days) | The mean time to GTN diagnosis ranged across control groups from 35.7 days to 59.5 days. | The mean time to GTN diagnosis in the intervention groups was 65.5 days to 81.8 days (higher). | MD 28.72 (13.19 to 44.24) | 33 women | ⊕⊕⊝⊝ | We downgraded this evidence because the meta‐analysis included 1 study of poor methodological quality (Kim 1986). When this study was excluded, the results of the remaining study (Limpongsanurak 2001; 19 women) were: MD 22.30; 95% CI −9.05 to 53.65. |
| Number of courses of chemotherapy to cure | The mean number of courses of chemotherapy required to cure subsequent GTN was 1.4 courses (10 women). | The mean number of courses of chemotherapy required to cure subsequent GTN was 2.5 courses (4 women). | MD 1.10 (0.52 to 1.68) | 14 women | ⊕⊝⊝⊝ | This analysis only included 1 study, and we considered to be of a poor methodological quality (Kim 1986). |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| The assumed risk for the mixed‐risk population was calculated by using the weighted mean risk across the control group for this outcome. The assumed risk for the high‐risk population was based on the control group of Limpongsanurak 2001, which was the only study to evaluate a high‐risk population only. | ||||||
| Prognostic factor | Score | |||
| 0 | 1 | 2 | 3 | |
| U/S diagnosis | Partial | Complete | Recurrent | |
| Uterine size for GA (months) | not more than 1 | > 1 | > 2 | > 3 |
| hCG level (mIU/mL) | < 50,000 | > 50,000 to < 100,000 | > 100,000 to < 1,000,000 | > 1,000,000 |
| Diameter of theca lutein cysts (cm) | ‐ | < 6 | < 6 to < 10 | > 10 |
| Patient age (years) | ‐ | < 20 | ≥ 40 | > 50 |
| Medical complications** | ‐ | ≥ 1 | ‐ | ‐ |
| *From Berkowitz 1987 Low risk is defined as a score of < 4; high risk is defined as a score ≥ 4 U/S: ultrasound; GA: gestational age, hCG: β‐human chorionic gonadotrophin. ** hyperemesis, hyperthyroidism, pre‐eclampsia, trophoblastic embolisation, disseminated intravascular coagulation. | ||||
| Study | Design | Participants (P‐Chem) | Participants (control/no P‐Chem) | Intervention | Rate of GTN (P‐Chem) | Rate of GTN (control) | Comments |
| Case‐control | 107 women (HM) | 42 women (HM) | Methotrexate 10 mg/day PO × 7 days given within 3 weeks of ERPC. | 2/107 (2%) | 4/42 (10%) | No choriocarcinoma observed in the P‐Chem group vs 3/42 in the control group. Toxic side effects occurred in 84/107 women, including stomatitis (34/107) and myelosuppression (22/107). | |
| Prospective case‐control | 73 women (CM) | 116 women (CM) | 3 intervention arms: methotrexate 0.3 mg/kg/day × 5 days (20 women); or dactinomycin 9 to 12 μg/kg/day × 5 days (53 women); ERPC on day 3. | 6/73 (8%) | 23/116 (20%) | No metastatic disease observed in the P‐Chem groups. P‐Chem well tolerated with minor side effects. | |
| Prospective case‐control | 100 women (HM) | 100 women (HM) | Dactinomycin 12 μg/kg/day × 5 days. ERPC on day 3. | 2/100 (2%) | 16/100 (16%) | No metastatic disease observed in the P‐Chem group vs 4/100 in the control group (4%). Reversible alopecia occurred in 32% of the P‐Chem group. No serious toxic reactions. | |
| Prospective case‐control | 174 women (CM) | 858 women (CM) | Dactinomycin 12 μg/kg/day × 5 days. ERPC on day 3. | 10/247 (4%) | 160/858 (19%) | No metastatic disease observed in the P‐Chem group vs 34/858 (4%) in the control group. This report includes data from Goldstein 1974. | |
| Retrospective case‐control | 104 women (92% CM) | 250 women (CM) | Methotrexate 10 mg/day PO × 5 days every 3 weeks for 3 cycles. | 3/104 (3%) | 23/250 (9%) | Significantly fewer high‐risk women in the P‐Chem group (1/47) vs the control group (18/126) developed GTN (2% vs 14%; P < 0.05). 2 women had severe myelosuppression and 1 had severe alopecia. | |
| RCT (?) | 293 women (CM) | 127 women (CM) | Methotrexate 10 mg/day (IM or PO) for 7 days, within 3 weeks of evacuation. | 22/293 (7%) | 23/127 (18%) | There were 5 cases of metastatic disease in each group (1.7% vs 3.9%, respectively) 27.3% of the P‐Chem group experienced drug‐related side effects including stomatitis (10.3%), nausea/vomiting (6.8%) and leukopenia (4.4%). However none were reported to be severe. | |
| RCT | 39/71 women (CM; 18/31 low‐risk and 21/40 high‐risk women) | 32 women (CM) | Methotrexate 1.0 mg/kg/day IM (days 1, 3, 5, 7) and citrovorum factor rescue 0.1 mg/kg/day IM (days 2, 4, 6, 8). ERPC on day 3. | 4/39 (10%) | 10/32 (31%) | Significantly fewer high‐risk women in the P‐Chem group (14%) vs the control group (47%) developed GTN. There was no significant difference in the GTN rates of low‐risk women between groups. | |
| Retrospective case‐control | 52 women (14 low‐risk, 21 medium‐risk and 17 high‐risk HM) | 88 women (38 low‐risk, 25 medium‐risk and 25 high‐risk HM) | Methotrexate 1 mg/kg (days 1, 3, 5, 7) and citrovorum factor (0.1 mg/kg (days 2, 4, 6, 8); or dactinomycin 12 μg/kg/day × 5 days started at the time of ERPC. | 8/52 (15.4%) | 28/88 (31.8%) | Significantly fewer high‐risk women in the P‐Chem group (7/17) vs the control group (22/25) developed GTN (41% vs 88%; P < 0.01). There was no significant difference in the GTN rates in low‐ and medium‐risk women between groups. The time to achieve normal hCG levels was shorter in high‐risk women in the P‐Chem group. | |
| Double‐blind RCT | 30 women (high‐risk CM) | 30 women (high risk CM) | Dactinomycin 10 µg/kg for 5 days, within 1 week after ERPC and histology. | 4/29 (15.4%) | 15/30 (50%) | Mild, reversible side effects reported including stomatitis (10%), nausea/vomiting (10%), oral ulcers (3.3%) and hair loss (13.3%) ‒ all grade 1 except for 2 women with grade 2 patchy alopecia. | |
| Retrospective case‐control | 29 adolescents (high‐risk CM) | 31 adolescents (high‐risk CM) | Dactinomycin 1.25 mg/m² IV given 1 hour before ERPC. | 2/29 (6.9%) | 9/31 (29%) | Mean risk scores and hCG levels were significantly higher and gestational age was significantly lower in the P‐Chem group than the control group. Mild and transient side effects included hepatotoxicity (10%) and mild alopecia (6.8%). | |
| Retrospective case‐control | 163 women (high risk, > 90% CM) | 102 women (high risk, > 90% CM) | Dactinomycin 1.25 mg/m² IV given 1 hour before ERPC. | 30/163 (18.4%) | 35/102 (34.3%) | Mild and transient side effects including nausea (8%), raised liver enzymes (3.7%), stomatitis (3.1%), rash (2.4%) diarrhoea (2.4%), alopecia (1.2%) and neutropenia (0.6%) were seen in 21% of the P‐Chem group. Time to GTN diagnosis, subsequent drug resistance and the number of chemotherapy course to cure was similar in the 2 groups. | |
| * Three studies administered P‐Chem after ERPC including Koga 1968, Kashimura 1986 and Limpongsanurak 2001. CM; complete mole; ERPC: evacuation of retained products of conception; GTN: gestational trophoblastic neoplasia; HM: hydatidiform mole; IM: intramuscular; IV: intravenous; P‐Chem; prophylactic chemotherapy; PO: per os; RCT: randomised controlled trial. | |||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Incidence of GTN (overall) Show forest plot | 3 | 550 | Risk Ratio (M‐H, Random, 95% CI) | 0.37 [0.24, 0.57] |
| 1.1 Methotrexate prophylaxis | 2 | 491 | Risk Ratio (M‐H, Random, 95% CI) | 0.39 [0.24, 0.64] |
| 1.2 Dactinomycin prophylaxis | 1 | 59 | Risk Ratio (M‐H, Random, 95% CI) | 0.28 [0.10, 0.73] |
| 2 Incidence of GTN (high‐risk HM only) Show forest plot | 2 | 99 | Risk Ratio (M‐H, Random, 95% CI) | 0.29 [0.14, 0.60] |
| 2.1 Methotrexate prophylaxis | 1 | 40 | Risk Ratio (M‐H, Random, 95% CI) | 0.30 [0.10, 0.95] |
| 2.2 Dactinomycin prophylaxis | 1 | 59 | Risk Ratio (M‐H, Random, 95% CI) | 0.28 [0.10, 0.73] |
| 3 Time to GTN diagnosis Show forest plot | 2 | 33 | Mean Difference (IV, Random, 95% CI) | 28.72 [13.19, 44.24] |
| 3.1 Methotrexate prophylaxis | 1 | 14 | Mean Difference (IV, Random, 95% CI) | 30.80 [12.93, 48.67] |
| 3.2 Dactinomycin prophylaxis | 1 | 19 | Mean Difference (IV, Random, 95% CI) | 22.30 [‐9.05, 53.65] |
| 4 Number of courses of chemotherapy to cure Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 4.1 Methotrexate prophylaxis | 1 | 14 | Mean Difference (IV, Random, 95% CI) | 1.1 [0.52, 1.68] |
| 5 Mortality rate Show forest plot | 1 | Risk Ratio (M‐H, Random, 95% CI) | Subtotals only | |
