Table 2.
Comparative studies of P‐Chem for hydatidiform mole
| Study | Design | Participants (P‐Chem) |
Participants (control/no P‐Chem) |
Intervention | Rate of GTN (P‐Chem) | Rate of GTN (control) | Comments |
| Koga 1968* | Case‐control | 107 women (HM) | 42 women (HM) | Methotrexate 10 mg/day PO x 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) |
| Goldstein 1971 | Prospective case‐control | 73 women (CM) | 116 women (CM) | 3 intervention arms: methotrexate 0.3 mg/kg/day x 5 days (20 women); or dactinomycin 9‐12 μg/kg/day x 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 |
| Goldstein 1974 | Prospective case‐control | 100 women (HM) | 100 women (HM) | Dactinomycin 12 μg/kg/day x 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 |
| Goldstein 1981 | Prospective case‐control | 174 women (CM) | 858 women (CM) | Dactinomycin 12 μg/kg/day x 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 |
| Fasoli 1982 | Retrospective case‐control | 104 women (92% CM) | 250 women (CM) | Methotrexate 10 mg/day PO x 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 |
| Kashimura 1986* | 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 |
| Kim 1986 | 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 |
| Park 1996 | 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 x 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 |
| Limpongsanurak 2001* | 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 |
| Uberti 2006 | 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%) |
| Uberti 2009 | 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.