Technique of Single-Agent Treatment patients were randomized to receive either biweekly ActD 1.25mg/m2 intravenous (IV) bolus or weekly MTX 30 mg/m2 intramuscular (IM). The remission rate was 58% in the MTX arm and 73% in the ActD arm. These results suggest that ActD is superior to the weekly MTX regimen in treating low-risk GTN. Before recommending pulse ActD as the primary modality in the treatment of patients with low-risk GTN, it is important to be aware of the potential for significant toxicity of this regimen compared to those receiving MTX. All patients with low-risk disease in this study ultimately achieved remission, regardless of their initial response. Regarding the true comparative effectiveness of these agents, it would be prudent to compare the biweekly ActD regimen to the more commonly used 5-day or 8-day MTX regimens, which offer a high initial remission rate with minimal toxicity.
The administration of methotrexate with folinic acid (MTX-FA) in GTN to limit systemic toxicity was first reported in 1964 (71).Subsequently, it has been confirmed that MTX-FA is both effective and safe in the management of GTN.
An evaluation of 185 patients treated with MTX-FA revealed that complete remission was achieved in 162 patients (87.6%); of these patients, 132 (81.5%) required only one course of MTX-FA to attain remission (72). MTX-FA induced remission in 147 of 163 patients (90.2%) with stage I GTN and in 15 of 22 patients (68.2%) with low-risk stages II and III GTN. Resistance to therapy was more common in patients with choriocarcinoma, metastasis, and pretreatment serum hCG levels higher than 50,000 mIU/mL. After treatment with MTX-FA, thrombocytopenia, granulocytopenia, and hepatotoxicity developed in 3 (1.6%), 11 (5.9%), and 26 (14.1%) patients, respectively. Thus, MTX-FA achieved an excellent therapeutic outcome with minimal toxicity and attained this goal with limited exposure to chemotherapy.
The serum hCG level is measured weekly after each course of chemotherapy. The hCG regression curve serves as the primary basis for determining the need for additional treatment.
After the first treatment: 1.
Further chemotherapy is withheld as long as the hCG level is falling progressively.
2.
Additional single-agent chemotherapy is not administered at any predetermined or fixed interval.
A second course of chemotherapy is administered under the following conditions: 1.
If the hCG level plateaus for more than 3 consecutive weeks or begins to rise again.
2.
If the hCG level does not decline by 1 log within 18 days after completion of the first treatment.
If the patient’s response to the first treatment was adequate and a second course of MTXFA is required, the dosage of MTX is unaltered. An adequate response is defined as a fall in the hCG level by 1 log after a course of chemotherapy.
If the response to the first treatment is inadequate, the dosage of MTX is increased from 1.0 mg/kg/day to 1.5 mg/kg/day for each of the 4 treatment days. If the response to two consecutive courses of MTX-FA is inadequate, the patient is considered to be resistant to MTX, and ActD is promptly substituted. If the hCG levels do not decline by 1 log after treatment with ActD, the patient is considered resistant to ActD as a single agent. She must be treated intensively with combination chemotherapy to achieve remission.
Management of Refractory GTN