Evolution of treatment of high-risk metastatic gestational trophoblastic tumors: Ain Shams University experience

Abstract

The aim of the current study is to evaluate the different treatment modalities used in the management of high-risk metastatic gestational trophoblastic tumors (GTT) between June 1992 and December 2004 at the Gynecologic Oncology Unit, Ain Shams University. Out of 261 patients diagnosed and treated for GTT, 70 (26.8%) were high risk metastatic patients based on the National Institutes of Health clinical classification. The mean age was 29.39 +/- 9.38 years (16-55 years), with six patients (8.6%) being older than 39 years, and the mean duration of follow-up was 79.74 +/- 40.44 months (6-157 months). Forty patients (57.14%) were diagnosed after molar pregnancy, 22 (31.43%) after abortion, and 8 (11.43%) after term pregnancy. Forty-two patients (60%) were diagnosed within 4 months of the occurrence of the disease, and 28 (40%) were diagnosed after more than 4 months. Sixty-seven patients were treated using different regimens according to the protocol of treatment at that time. The MAC regimen was used initially but has been subsequently abandoned in favor of EMA-CO (etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine [Oncovin]) regimen, which was later modified by omitting the CO arm to decrease its toxicity. If resistance developed, platinum-based therapy was given in the form of EMA-EP. Recently, our unit incorporated paclitaxel in the third-line treatment. Surgical intervention was used selectively. Fifty-seven (81.4%) patients could be cured; 43 by initial chemotherapy, with a mean of 7 +/- 0.46 courses (6-15), and 14 were salvaged by second- or third-line chemotherapy. Fourteen patients (20%) died during the study period; one was unrelated to GTT, while three died of acute respiratory distress syndrome before instituting proper therapy and two died of treatment complications. Using univariate and multivariate Cox regression analyses, the presence of brain and/or liver metastases was found to be the worst prognostic variable affecting the survival, followed by resistance to combination chemotherapy and then the type of antecedent pregnancy. The projected 5-year survival as estimated by Kaplan-Meier method was 78%.

Profile of Mortality Among Women With Gestational Trophoblastic Disease Infected With the Human Immunodeficiency Virus (HIV): Argument for a New Poor Prognostic Factor

“…A statistically significant increase in mortality (88%) was noted among HIV-infected patients with CD4 counts less than 200 cells/KL in the background of widespread metastases and comorbid illnesses (P = 0.001). El-Lamie et al, 10 in a retrospective report of 261 patients treated for GTD, during an 11-year period documented a 20% mortality rate among HIV-noninfected patients. Review of the 17 HIV-infected patients in this study who were treated and survived demonstrated that they were admitted in good general condition with no comorbidities, and 15 of 16 patients had CD4 counts greater than 200 cells/KL.…”

Treatment of high-risk gestational trophoblastic neoplasia with weekly high-dose methotrexate–etoposide

“…EMA-CO has relatively low toxicity, with grade 3/4 myelosuppresion in less than 2% of chemotherapy cycles [18]. Complete response rates of 71-78% and long-term survival rates of 85-94% have been reported, but approximately 25-30% of patients became refractory or experienced a relapse and required subsequent salvage chemotherapy with platinum-containing multi-agent regimens [1,6]. However, no randomized trials have been conducted to prove its superiority, thus EMA-CO could not be compared to other existing regimens in a recent Cochrane review [19].…”

“…The most commonly administered multiagent regimen for high-risk GTN is etoposide, methotrexate and dactinomycin, alternating every week with cyclophosphamide and vincristine (EMA-CO) [5], which is relatively well-tolerated, and has a high cumulative 5-year survival rate [2]. However, approximately 25-30% of high-risk patients will require salvage chemotherapy with platinum-containing multi-agent regimens [1,6]. Moreover, disappointing results were seen in case of brain and liver metastases, with a long-term survival of 70% and 27% respectively, and only 10% when both sites were involved [7,8].…”

Invasive Hydatidiform Mole Showing Resistance to Single Etoposide Chemotherapy

“…Chemotherapy is considered to be effective when the level of serum hCG after the chemotherapy decreases to one tenth of all observed pretreatment levels. A change of chemotherapy regimen is indicated in the following conditions: 1. the serum hCG level rises by more than 10% for two to three consecutive values within a 1-to 2-week interval; 2. the serum hCG level plateaus (±10%) for 2-3 weeks; 3. new metastases appear 19) . The serum hCG level of the present case dropped to 58 mIU/mL after the third single etoposide chemotherapy.…”

“…About 20% of cases become chemoresistant and require multi-agent chemotherapy. Chemotherapy with MAC is effective for many diseases when they show resistance to single agent chemotherapy 19) . After diagnosis of a molar pregnancy, follow-up is essential to detect patients who require chemotherapy 20) .…”