Prophylactic actinomycin D for high-risk complete hydatidiform mole. Effects of prophylactic chemotherapy for persistent trophoblastic disease in patients with complete hydatidiform mole. Prophylactic chemotherapy for hydatidiform mole. Five to 15 years follow-up.
To evaluate the effectiveness of one course of prophylactic actinomycin D in reducing the malignant sequelae requiring chemotherapy in high-risk complete hydatidiform mole (CHM).
                A double-blind, randomized, controlled clinical trial was carried out at King Chulalongkorn Memorial Hospital. Sixty cases of CHM classified as high risk were recruited and randomly allocated to a chemoprophylactic or control group. Within one week after evacuation of molar tissues, actinomycin D was administered in the chemoprophylactic group. Patients in the control group were given only intravenous fluid and analgesic drugs. The number of patients with malignant sequelae who required therapeutic chemotherapy after evacuation of hydatidiform mole in each group was recorded.
                The incidence of malignant sequelae was 13.8% (95% confidence interval [CI] = 3.9-31.7%) in the chemoprophylactic group and 50.0% (95% CI = 31.3-68.7%) in the control group. The risk reduction of malignant sequelae with one course of actinomycin D chemoprophylaxis in high-risk CHM was 72.4% (95% CI = 26.7-89.6%) (P = .005). The side effects of prophylactic chemotherapy were stomatitis, nausea/vomiting, sore throat with oral ulcer and hair loss.
                One course of actinomycin D given as chemoprophylaxis decreased by 72.4% malignant sequelae after evacuation of molar tissue in patients with high-risk CHM. This may be particularly beneficial in patients with high-risk CHM who cannot be followed closely, whose compliance is in question and for whom hormonal follow-up is not available or unreliable. Seventy-one patients with complete hydatidiform mole were prospectively randomized into two groups: one group (39 patients) was treated with a single course of methotrexate and citrovorum factor rescue as chemoprophylaxis; the other group (32 patients) was not treated. After molar evacuation, four patients from the treated group (10.3%) and ten patients from the untreated group (31.3%) developed persistent trophoblastic disease. The time interval from evacuation of the mole to diagnosis of persistent trophoblastic disease was longer in the treated group than in the untreated group (9.5 +/- 2.4 weeks versus 5.1 +/- 1.6 weeks, P less than .05). Among high-risk patients, there was a lower incidence of persistent trophoblastic disease in the treated group than in the untreated group (14.3 versus 47.4%, P less than .05). Among low-risk patients there was no difference between the groups (5.6 versus 7.7%, P greater than .05). All 14 patients with persistent trophoblastic disease achieved complete remission with therapeutic chemotherapy. More courses of chemotherapy were required until complete remission in the treated group than in the untreated group (2.5 +/- 0.5 versus 1.4 +/- 0.5, P less than .005). These findings suggest that even though chemoprophylaxis reduces the incidence of persistent trophoblastic disease in patients at high risk, it increases tumor resistance and morbidity. Although prophylactic chemotherapy with methotrexate and citrovorum factor rescue may be helpful for high-risk patients who cannot be followed or whose compliance is in question, careful follow-up remains the most important way to identify patients who should receive chemotherapy. The effectiveness of the prophylactic chemotherapy was evaluated in 420 patients with molar pregnancy. All patients were followed for 5 to 15 years after the evacuation. Twenty-two (7.5%) of 293 patients with prophylactic chemotherapy and 23 (18.1%) of 127 patients without prophylactic chemotherapy (control) developed secondary trophoblastic disease. The prophylactic chemotherapy could reduce the occurrence of secondary trophoblastic disease. In these secondary trophoblastic diseases, 5 (22.7%) of 22 patients in the prophylactic chemotherapy group and 5 (21.7%) of 23 in the control had metastatic trophoblastic disease. Choriocarcinoma after the molar pregnancy developed in two patients (0.7%) of the prophylactic chemotherapy group and two (1.6%) of the control. Prophylactic chemotherapy did not eliminate the occurrence of choriocarcinoma. The complication of the prophylactic chemotherapy was seen in 27.3% of the patients. Neither severe complication nor death were related to the toxicity.