levoleucovorin and Hydatidiform-Mole

This is an update of the original review that was published in The Cochrane Database of Systematic Reviews, 2009, Issue 2. Gestational trophoblastic neoplasia (GTN) are malignant disorders of the placenta that include invasive hydatidiform mole, choriocarcinoma, placental-site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT). Choriocarcinoma and invasive hydatidiform mole respond well to chemotherapy: low-risk tumours are treated with single-agent chemotherapy (e.g. methotrexate or actinomycin D), whereas high-risk tumours are treated with combination chemotherapy (e.g. EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine)). Various drug combinations may be used for high-risk tumours; however, the comparative efficacy and safety of these regimens is not clear.. To determine the efficacy and safety of combination chemotherapy in treating high-risk GTN.. For the original review, we searched the Cochrane Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2008), MEDLINE, EMBASE and CBM in May 2008. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to September 2012. In addition, we searched online clinical trial registries for ongoing trials.. Randomised controlled trials (RCTs) and quasi-RCTs comparing first-line combination chemotherapy interventions in women with high-risk GTN.. Two review authors independently collected data using a data extraction form. Meta-analysis could not be performed as we included only one study.. We included one RCT of 42 women with high-risk GTN who were randomised to MAC (methotrexate, actinomycin D and chlorambucil) or the modified CHAMOCA regimen (cyclophosphamide, hydroxyurea, actinomycin D, methotrexate, doxorubicin, melphalan and vincristine). There were no statistically significant differences in efficacy of the two regimens; however women in the MAC group experienced statistically significantly less toxicity overall and less haematological toxicity than women in the CHAMOCA group. During the study period, six women in the CHAMOCA group died compared with one in the MAC group. This study was stopped early due to unacceptable levels of toxicity in the CHAMOCA group. We identified no RCTs comparing EMA/CO with MAC or other chemotherapy regimens.. CHAMOCA is not recommended for GTN treatment as it is more toxic and not more effective than MAC. EMA/CO is currently the most widely used first-line combination chemotherapy for high-risk GTN, although this regimen has not been rigorously compared to other combinations such as MAC or FAV in RCTs. Other regimens may be associated with less acute toxicity than EMA/CO; however, proper evaluation of these combinations in high-quality RCTs that include long-term surveillance for secondary cancers is required. We acknowledge that, given the low incidence of GTN, RCTs in this field are difficult to conduct, hence multicentre collaboration is necessary.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Doxorubicin; Early Termination of Clinical Trials; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Hydroxyurea; Leucovorin; Melphalan; Methotrexate; Pregnancy; Trophoblastic Tumor, Placental Site; Vincristine

Using data primarily from Charing Cross Hospital in London, we examined the organization and funding of patients' care and follow-up, the value of second evacuations, the indications for treatment escalation and the results of treating patients with persistent low levels of human chorionic gonadotropin (hCG) following a molar pregnancy. In the U.K. system the total cost per patient treated is approximately $30,000. Second evacuations appear to have only a modest chance (18%) of benefit in patients with hCG levels over 5,000 IU/L. Outcome analysis of patients with low-risk gestational trophoblastic tumor (GTT) treated with methotrexate/folinic acid indicates that hCG levels in excess of500 IU/L at 7 weeks after starting are an accurate predictor of impending methotrexate resistance. For patients with hCG values under 100 IU/L at the time of treatment, a review of the 30 most recent low-risk GTT patients demonstrates a 100% cure rate with standard treatment. Low-risk GTT following a molar pregnancy is a highly curable malignancy, and cure rates approaching 100% should be expected. National or regional organization of follow-up and treatment is simple, economic and associated with enhanced outcomes when appropriate treatment policies are followed.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Drug Resistance, Neoplasm; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Neoplasm Recurrence, Local; Pregnancy; Risk Assessment; Treatment Outcome; Uterine Neoplasms

Gestational trophoblastic disease (GTD) includes gestational trophoblastic tumour and hydatidiform mole. Many women of reproductive age are affected by this disease although its incidence differs by geographical location. A number of chemotherapy regimens are used for treating the disease, such as methotrexate, actinomycin D and cyclophosphamide (MAC), methotrexate, actinomycin D, cyclophosphamide, doxorubicin, melphalan, hydroxyurea and vincristine (CHAMOC), etoposide, methotrexate and actinomycin (EMA) plus cyclophosphamide and vincristine (CO) (EMA-CO), etoposide, methotrexate and actinomycin (EMA) plus etoposide and cisplatin(EP) (EMA-EP). The efficacy of these drugs has not been systematically reviewed.. To determine the efficacy and safety of combination chemotherapy in treating high-risk GTT.. Electronic searches of MEDLINE, EMB, Cochrane Central Register of Controlled Trials (CENTRAL) and CBM were carried out. Four journals were handsearched and other searching methods were used for identifying more studies.. The review included randomized controlled trials (RCTs) or quasi-RCTs of combination chemotherapy for treating high-risk GTT. Patients with placental-site trophoblastic tumour (PSTT), who had received chemotherapy in the previous two weeks, or patients with chemotherapy intolerance were excluded.. Two investigators independently collected data using a data extraction form. Meta-analysis was not performed and the review was conducted as a narrative review.. One study with 42 participants was included in this review. It indicated that a MAC regimen was better than a CHAMOCA regimen for high-risk GTT because of lower toxicity. The quality of the study was unclear.. The methodological limitations of the included study prevent any firm conclusions about the best combination chemotherapy regimen for high-risk GTT. High quality studies are required.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Doxorubicin; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Hydroxyurea; Leucovorin; Methotrexate; Pregnancy; Trophoblastic Tumor, Placental Site; Vincristine

Gestational trophoblastic disease is a fascinating group of pregnancy disorders characterised by abnormal proliferation of trophoblast, ranging from benign to malignant. Because the disease is uncommon, there is a need to formulate management with the assistance of collective information.. A review of available information from English written literature was undertaken, especially data reported by registries around the world (Charing Cross Hospital in England, the North-western University and the New England area in the USA as well as our own experience in Queensland, Australia). Where possible, collated data from relevant studies were analysed to answer some of the questions posed in clinical practice, with reference to metastatic disease to liver and brain, twinning of molar gestation and coexisting fetus, and placental-site tumour.. We found that molar gestation can be classified according to its clinical presentation which influences the time taken to reach human chorionic gonadotropin (HCG) 'negativity' and the risk of persisting disease. Categorisation of risk is the basis for choice of chemotherapy to achieve good outcomes. Metastases to liver and brain remain problems in management; the development of 'new' metastases during chemotherapy is a very poor prognostic factor. In the variant of twinning with molar gestation and coexisting fetus, it is important to elucidate the fetal karyotype in planning management: a 69XXX fetus is not salvageable but a normal 46XX or 46XY fetus faces the prospect of early preterm delivery. The placental-site tumour is very rare; localised disease is curable by surgery; chemotherapy is less effective in disseminated disease. From collated worldwide data, the recurrence rate after one mole is 1.3% and after two or more is 20%. Reproductive outcome in subsequent pregnancies, even after multidrug chemotherapy, is not different from the general population. Because of the increased risk long-term of second tumours after multidrug chemotherapy a closer surveillance of these patients is necessary.. In general, the disease in its persisting or malignant form is 'a cancer model par excellence' because of an identifiable precursor condition, a reliable HCG marker, and sensitivity of the disease to cytotoxic drugs. With current management, retention of fertility is possible and normal reproductive outcome assured.

Topics: Brain Neoplasms; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Leucovorin; Liver Neoplasms; Methotrexate; Neoplasms, Second Primary; Pregnancy; Queensland; Recurrence; Registries

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.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Female; Humans; Hydatidiform Mole; Korea; Leucovorin; Methotrexate; Pregnancy; Prospective Studies; Random Allocation; Risk; Suction; Time Factors; Trophoblastic Neoplasms; Uterine Neoplasms

Fifteen patients with nonmetastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor. Complete and sustained remission was achieved in 14 of the 15 patients. Response to treatment was determined solely on the basis of serial serum human chorionic gonadotropin levels as measured by the beta subunit radioimmunoassay. All patients developed nonmetastatic gestational trophoblastic neoplasms following evacuation of a molar pregnancy. The known histologic diagnosis in all cases was hydatidiform mole. No significant toxicity was encountered despite careful monitoring of marrow, hepatic, renal, neurologic, and mucocutaneous parameters. Up to January 31, 1976, duration of remission ranged from 2 to 14 months.

Topics: Adolescent; Adult; Clinical Trials as Topic; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Parity; Pregnancy; Remission, Spontaneous; Trophoblastic Neoplasms; Uterine Neoplasms

The risk of malignant transformation of molar pregnancies after human chorionic gonadotropin levels return to normal is low, roughly 0.4%, but may justify an adaptation of monitoring strategies for certain patients.. This study aimed to determine the risk of gestational trophoblastic neoplasia after human chorionic gonadotropin normalization in women with molar pregnancy and identify risk factors for this type of malignant transformation to optimize follow-up protocols after human chorionic gonadotropin normalization.. This was a retrospective observational national cohort study based at the French National Center for Trophoblastic Diseases of 7761 patients, treated between 1999 and 2020 for gestational trophoblastic disease, whose human chorionic gonadotropin levels returned spontaneously to normal.. Among 7761 patients whose human chorionic gonadotropin levels returned to normal, 20 (0.26%) developed gestational trophoblastic neoplasia. The risk of malignant transformation varied with the type of mole, from 0% (0 of 2592 cases) for histologically proven partial mole to 0.36% for complete mole (18 of 5045) and 2.1% (2 of 95) for twin molar pregnancy. The median time to diagnosis of malignant transformation after human chorionic gonadotropin normalization was 11.4 months (range, 1-34 months). At diagnosis, 16 of 20 patients (80%) had the International Federation of Gynecology and Obstetrics stage I tumor, and 10 of 20 patients (50%) had a tumor classified as low risk in terms of the International Federation of Gynecology and Obstetrics score. In 9 of 20 patients (45%), the most common first-line treatment was combination chemotherapy. A quarter of these tumors (5 of 20) were histologically proven placental site or epithelioid trophoblastic tumors. In univariate analysis, the factors significantly associated with a higher risk of developing gestational trophoblastic neoplasia after the end of the normal human chorionic gonadotropin monitoring period were age of ≥45 years (odds ratio, 8.3; 95% confidence interval, 2.0-32.7; P=.004) and time to human chorionic gonadotropin normalization of ≥8 weeks (odds ratio, 7.7; 95% confidence interval, 1.1-335; P=.03). The risk was even higher for human chorionic gonadotropin normalization times of ≥17 weeks (odds ratio, 19.5; 95% confidence interval, 3.3-206; P<.001).. In this group of patients with gestational trophoblastic disease, none of the those with pathologically verified partial mole had malignant transformation, supporting the current recommendation of stopping human chorionic gonadotropin monitoring after 3 successive negative tests. In cases of complete mole or twin molar pregnancy, we proposed to extend the monitoring period with quarterly human chorionic gonadotropin measurements for an additional 30 months in patients with the identified risk factors for late malignant transformation (age, ≥45 years; time to human chorionic gonadotropin normalization, ≥8 weeks).

Topics: Adolescent; Adult; Aftercare; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cell Transformation, Neoplastic; Choriocarcinoma; Chorionic Gonadotropin; Cisplatin; Cyclophosphamide; Dactinomycin; Etoposide; Female; France; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Hysterectomy; Leucovorin; Methotrexate; Middle Aged; Neoplasm Staging; Pregnancy; Retrospective Studies; Trophoblastic Tumor, Placental Site; Uterine Neoplasms; Vincristine; Young Adult

Gestational Trophoblastic Neoplasia (GTN) is used to describe a group of malignant gestational tumors originating from the placenta. The chance of having malignant GTN is high in a high-risk molar pregnancy. The main aim of this study is to investigate the effectiveness of using prophylactic chemotherapy in high-risk molar pregnancy to prevent malignant GTN.. In this case-control retrospective study, all patients with high-risk mole referred to Firoozgar and Akbarabadi Hospitals affiliated with Iran University of Medical Sciences (IUMS) from 2003 to 2013 were divided into two groups of recipient and non-recipient of methotrexate prophylactic chemotherapy.Demographic information including age, parity, weight, serum βHCG before and after the intervention, level of liver function tests (LFT) and GTN were analyzed.. There were 102 patients with a mean age of 27.13 years (SD= 0.37), and 51 patients (50 %) received prophylactic Methotrexate (MTX), and others were the non-receivers. Finally, 23 patients (22.5%) were inflicted with GTN, and 79 (77.5 %) did not. The average time of βHCG spontaneous remission between the groups were 2.5 (SD=1.33) and 3.2 (SD=1.21), for the recipient and non-recipient, respectively, which showed a significant difference (p).. This study concludes that prophylactic chemotherapy with MTX and leucovorin may be capable of reducing GTN, which supports the prescription of MTX in high-risk mole, especially in countries with limited resources. The toxicity of methotrexate can be reduced with the addition of leucovorin.
.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Case-Control Studies; Dactinomycin; Female; Follow-Up Studies; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Pregnancy; Prognosis; Retrospective Studies; Uterine Neoplasms

To assess the outcomes and toxicity of first-line methotrexate (MTX) chemotherapy in low-risk postmolar gestational trophoblastic neoplasia (GTN) patients receiving 8-day methotrexate or one-day methotrexate infusion regimens.. This retrospective cohort study was conducted at the New England Trophoblastic Disease Center (NETDC), between 1974 and 2014, and included 325 patients with FIGO-defined low-risk postmolar GTN receiving first-line 8-day MTX/folinic acid (FA) or one-day MTX infusion and FA. Demographics, disease presentation, initial treatment plan, treatment outcome, and treatment-related adverse events were assessed.. Sustained remission (84% vs 62%, p<0.001) and need to switch to second-line therapy due to treatment-related adverse events (5.3% vs 0%, p=0.001) were higher for 8-day MTX/FA compared to one-day MTX infusion. MTX resistance, however, was more frequent with one-day MTX (34.5%) than with 8-day MTX/FA (7.3%, p<0.001). Relapse rates were similar with both regimens (3.0%). Compared to one-day MTX infusion, 8-day MTX/FA was associated with significantly higher gastrointestinal disorders (48% vs 24%), abnormal laboratory findings (48% vs 28%), eye disorders (37% vs 19%) and general disorders (22% vs 5%) (p<0.001). Only infection frequency did not differ between 8-day MTX/FA and one-day MTX infusion (20% vs 12%, p=0.083).. This is one of the largest studies to comprehensively catalogue toxicities associated with 8-day MTX/FA and one-day MTX infusion. Although treatment-related adverse events were more frequent with 8-day MTX/FA, these were all self-limited and resolved with no long-term sequelae. Given this and its higher effectiveness, 8-day MTX/FA remains the treatment of choice at NETDC for patients with low-risk postmolar GTN.

Topics: Adolescent; Adult; Antimetabolites, Antineoplastic; Chorionic Gonadotropin; Cohort Studies; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Infusions, Intravenous; Leucovorin; Methotrexate; Middle Aged; Neoplasm Staging; Pregnancy; Retrospective Studies; Risk Factors; Young Adult

To compare the outcomes of Brazilian patients with molar pregnancy who continue human chorionic gonadotropin (hCG) surveillance with those treated with chemotherapy when hCG was still positive, but falling at 6months after uterine evacuation.. Retrospective chart review of 12,526 patients with hydatidiform mole treated at one of nine Brazilian reference centers from January 1990 to May 2016.. At 6months from uterine evacuation, 96 (0.8%) patients had hCG levels raised but falling. In 15/96 (15.6%) patients, chemotherapy was initiated immediately per FIGO 2000 criteria, while 81/96 (84.4%) patients were managed expectantly. Among the latter, 65/81 (80.2%) achieved spontaneous remission and 16 (19.8%) developed postmolar gestational trophoblastic neoplasia (GTN). Patients who received chemotherapy following expectant management required more time for remission (11 versus 8months; p=0.001), had a greater interval between uterine evacuation and initiating chemotherapy (8 versus 6months; p<0.001), and presented with a median WHO/FIGO risk score higher than women treated according to FIGO 2000 criteria (4 versus 2, p=0.04), but there were no significant differences in the need for multiagent treatment regimens (1/15 versus 3/16 patients, p=0.60). None of the women relapsed, and no deaths occurred in either group.. In order to avoid unnecessary exposure of women to chemotherapy, we no longer follow the FIGO 2000 recommendation to treat all patients with molar pregnancy and hCG raised but falling at 6months after evacuation. Instead, we pursue close hormonal and radiological surveillance as the best strategy for these patients.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Brazil; Case-Control Studies; Chemotherapy, Adjuvant; Chorionic Gonadotropin; Cohort Studies; Cyclophosphamide; Dactinomycin; Etoposide; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Middle Aged; Neoplasm Staging; Pregnancy; Retrospective Studies; Treatment Outcome; Uterine Neoplasms; Vacuum Curettage; Vincristine; Watchful Waiting; Young Adult

Post-molar pregnancy gestational trophoblastic tumours (GTT) have been curable with chemotherapy treatment for over 50 years. Because of the rarity of the diagnosis, detailed structured information on prognosis, treatment escalations and outcome is limited.. We have reviewed the demographics, prognostic variables, treatment course and clinical outcomes for the post-mole GTT patients treated at Charing Cross Hospital between 2000 and 2009.. Of the 618 women studied, 547 had a diagnosis of complete mole, 13 complete mole with a twin conception and 58 partial moles. At the commencement of treatment, 94% of patients were in the FIGO low-risk group (score 0-6). For patients treated with single-agent methotrexate, the primary cure rate ranged from 75% for a FIGO score of 0-1 through to 31% for those with a FIGO score of 6.. In the setting of a formal follow-up programme, the expected cure rate for GTT after a molar pregnancy should be 100%. Prompt treatment and diagnosis should limit the exposure of most patients to combination chemotherapy. Because of the post-treatment relapse rate of 3% post-chemotherapy, hCG monitoring should be performed routinely.

Topics: Adult; Chorionic Gonadotropin; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Pregnancy; Prognosis; Retrospective Studies; Treatment Outcome

Post molar GTN was reported to occur in 7.5-20% of patients following evacuation of complete hydatidiform moles and in 2.5-7.5% following evacuation of partial moles. The role of uterine re-curettage in post molar GTN is not clear.. Study of the correlation of pre-evacuation and week- one level of hCG, and uterine re-curettage to the number of chemotherapy courses in treatment of post molar GTN.. This retrospective study included 29 cases of post molar GTN through reviewing their medical records.. There were 25 cases (86.21) of low risk, and 4 cases of high risk score (13.79%). The 3 year survival was 96.6%. There were non-significant correlation of age, parity, pre-evacuation level and hCG in week-1 to number of chemotherapy courses, while uterine re-curettage was significantly correlated to number of chemotherapy courses (p = 0.04).. Uterine re-curettage was significantly correlated to less number of chemotherapy courses in patients with post molar GTN (p = 0.04). Pre-evacuation and week-1 hCG were not correlated to number of chemotherapy cycles. A large prospective randomized trial to clarify the beneficial effect of uterine re-curettage is recommended.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chorionic Gonadotropin; Cisplatin; Dilatation and Curettage; Doxorubicin; Female; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Pregnancy; Retrospective Studies; Uterine Neoplasms; Young Adult

To assess the curative effect of a second curettage in patients with low-risk Persistent Trophoblastic Disease (PTD) after molar pregnancy.. A retrospective cohort survey was performed on 2122 patients registered with the Dutch Central Registry for Hydatidiform Moles between 1987 and 2003. Of these, 422 patients developed PTD. For various reasons, 128 patients were excluded. The study group comprised 85 patients with, according to the Dutch guidelines, low-risk PTD who underwent a second therapeutic curettage as a part of the treatment for PTD. The control group consisted of 209 patients with low-risk PTD who did not undergo a second curettage. Patients in the study and control group were classified for high/low-risk PTD according to the internationally accepted FIGO 2000 guidelines. Primary outcome measures were the need for chemotherapy and if applicable, the number of chemotherapy courses.. After second curettage, eight out of 85 patients (9.4%) did not need additional chemotherapy which significantly differs from the 209 patients in the control group who all needed chemotherapy (P < 0.001). A debulking effect of the second curettage was observed: a median of 6 courses (interquartile range 3 courses) in the control group versus 5 courses (interquartile range 3 courses) in the study group (P = 0.036). Four out of the 85 (4.8%) patients with a second curettage had a major complication (uterine perforation or hemorrhage), which was managed conservatively.. A second curettage cured 9.4% of patients with PTD in this historical cohort and reduces the number of courses of chemotherapy. A second curettage seems to benefit only a limited number of patients with PTD. A randomized controlled prospective trial is needed to confirm this observation.

Topics: Adult; Chorionic Gonadotropin; Cohort Studies; Curettage; Female; Gestational Trophoblastic Disease; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Neoplasm Staging; Pregnancy; Reoperation; Retrospective Studies

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin, beta Subunit, Human; Diagnosis, Differential; Female; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Parity; Pregnancy; Ultrasonography, Prenatal; Uterine Cervical Neoplasms

Twin pregnancy consisting of complete hydatidiform mole (H-mole) and a coexisting fetus occurs with an estimated incidence of 1 per 22,000-100,000 pregnancies. The incidence of this unusual twin pregnancy with complete H-mole and a coexisting fetus after in vitro fertilization and embryo transfer (IVF-ET) is not thought to be greater than that of general population. We present an unusual twin pregnancy with complete H-mole and a coexisting fetus that occurred following IVF-ET, which was terminated at 21 weeks of gestation and developed into nonmetastatic gestational trophoblastic tumor.

Topics: Abortion, Therapeutic; Abortion, Threatened; Adult; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Chorionic Gonadotropin, beta Subunit, Human; Combined Modality Therapy; Embryo Transfer; Female; Fertilization in Vitro; Humans; Hydatidiform Mole; Infant, Newborn; Leucovorin; Male; Methotrexate; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy, Multiple; Uterine Hemorrhage; Uterine Neoplasms

A case of seven consecutive hydatidiform moles is presented. All of her pregnancies revealed a molar pregnancy, 4 of which were demonstrated histopathologically. In the context of this study, the potential risk for malignant transformation and the obstetric outcome are highlighted. The literature regarding recurrent molar pregnancies is reviewed.

Topics: Adult; Antimetabolites, Antineoplastic; Female; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Pregnancy; Risk Factors; Uterine Neoplasms

Of 4257 patients with gestational trophoblastic disease (GTD) registered between 1986 and 1996 with the Trophoblastic Screening and Treatment Centre, Sheffield, 231 women required chemotherapy; 28 were treated 24 weeks or more after the initial evacuation of products of conception. In 18 patients late treatment was a result of a predetermined watch and wait policy on the part of the Centre; these patients formed the study group. Patients were identified from the Centre's computer database. The time interval from first evacuation (diagnosis) to start of chemotherapy was calculated for each patient. Hospital records were reviewed when the interval of observation was 24 weeks or greater to determine patient characteristics, treatment and outcome. Eighteen women were treated 'late' (according to Centre policy), with a median age of 30 years (range 21-57 years). The interval from diagnosis to treatment ranged from 24 to, in one case, 56 weeks (median 33 weeks). Fourteen of 18 women had complete moles, 3/18 had partial moles and one had unclassified disease. All women had low-risk disease and were treated with single-agent methotrexate; 17 were cured with this regimen, one also required salvage chemotherapy. In conclusion, where a successful surveillance programme is in operation for GTD, a wait and watch policy can be adopted without compromising patients whose definitive treatment is commenced more than 6 months after the initial diagnosis.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Dactinomycin; Databases as Topic; England; Etoposide; Female; Follow-Up Studies; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Pregnancy; Prognosis; Registries; Salvage Therapy; Time Factors; Treatment Outcome; Trophoblastic Neoplasms; Uterine Neoplasms

The current study was undertaken in order to identify the clinical characteristics and natural history, as well as methods of investigation and available therapy, of persistent gestational trophoblastic disease (GTD) following the evacuation of partial hydatidiform mole (PM).. Case reports of persistent GTD following the evacuation of partial mole, were searched using the Medline computerized retrieval system. There were 66 such cases (including 4 cases treated at our department), representing 2.9% of GTD following PM.. The mean age of the women at diagnosis was 28.4 years and mean gravidity was 2.99. The mean gestational age at diagnosis was 15.5 weeks and the mean uterine size was 13.6 weeks. The most common presenting symptom was vaginal bleeding. In the majority of the patients, the pre-evacuation diagnosis was incomplete or missed abortion.. Although the malignant potential of PM is low, persistent GTD may develop after PM and may even metastasize, it is usually responsive to single agent chemotherapy but may require combination chemotherapy. Therefore, after evacuation of PM, these women should be followed with serial serum b-hCG. Further research is needed to enable earlier identification of PM that eventually will develop persistent GTD.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Dactinomycin; Female; Humans; Hydatidiform Mole; Hysterectomy; Karyotyping; Leucovorin; Methotrexate; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

Gestational trophoblastic disease (GTD) forms a heterogeneous pool of clinically and histopathologically defined entities with different malignant potential. The clinicopathologic characteristics of 158 cases, including 110 complete hydatidiform moles (CHM), 13 invasive moles, 32 choriocarcinomas, two placental site nodules and one placental site trophoblastic tumor are reported. Of all cases, 63.9% showed spontaneous regression after D&C. 36.1% resulted in a persistent or metastatic (11.4%) disease, including 12 CHM. Lung is found to be the most common site of metastasis (61%). The median time between antecedent pregnancy and GTD was 4.4 months. 44% had an antecedent CHM, 16% a term pregnancy. The median complete remission rate was 91.2% with 5.3% recurrent disease. Three women died. Eight patients received adjuvant surgical therapy for chemoresistant foci. In general, management of GTD is interdisciplinary with an emphasis placed on individualized treatment. In most cases, exact histopathologic diagnosis of the trophoblastic lesion remains the gold standard for guiding clinical therapy. Currently, there are no reliable genetic or molecular biologic markers predicting an aggressive behavior of CHM. Thus, all lesions should be followed by serial measurements of serum-HCG. All cases of persistent GTD should be treated in specialized centers.

Topics: Adolescent; Adult; Age Factors; Brain Neoplasms; Choriocarcinoma; Drug Therapy, Combination; Female; Humans; Hydatidiform Mole; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Pregnancy; Risk Factors; Tomography, X-Ray Computed; Treatment Outcome; Trophoblastic Neoplasms; Trophoblastic Tumor, Placental Site; Uterine Neoplasms

We have characterized a high-affinity folate receptor in human molar placenta tissue. Radioligand binding exhibited characteristics typical of other high-affinity folate binding proteins. Those included, positive cooperativity, a tendency to increased binding affinity with decreasing receptor concentration, a slow ligand dissociation at pH 7.4 becoming rapid at pH 3.5, and inhibition by folate analogues. The folate receptor cross-reacted with antibodies against human milk folate binding protein, e.g. the syncytothrophoblastic layer of molar placenta tissue sections showed strongly positive immunostaining. The gel filtration profile contained two radioligand-bound peaks (25 and 100 kDa), however, with considerable overlap. Only a single band of 70 kDa was seen on SDS-PAGE immunoblotting. The folate receptor in placental tissue may play a crucial role in the transfer of folate from maternal circulation to the fetus.

Topics: Antidotes; Carrier Proteins; Enzyme-Linked Immunosorbent Assay; Female; Folate Receptors, GPI-Anchored; Folic Acid Antagonists; Humans; Hydatidiform Mole; Immunoblotting; Immunohistochemistry; Leucovorin; Methotrexate; Placenta; Pregnancy; Radioligand Assay; Receptors, Cell Surface; Trophoblasts; Uterine Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Chlorambucil; Cyclophosphamide; Dactinomycin; Drug Administration Schedule; Etoposide; Female; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Neoplasm Metastasis; Neoplasm Staging; Pregnancy; Prognosis; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

With increasing cost of medical care, newer methods of administering chemotherapy on an outpatient basis are being sought to reduce the need for hospitalization and protracted losses of valuable time for patients with nonmetastatic gestational trophoblastic neoplasia (NMGTN). To achieve this end, two NMGTN patients were treated with a single course of one dose of methotrexate (MTX) followed by multidose Citrovorum Factor (CF) without observing the expected response. Failure to respond appeared to be due to the schedule of administration. Although the dose and plasma concentrations of MTX were considered to be adequate for cell kill, fractionation--as established by conventional schedules of MTX administration--appeared necessary for response by exposing the maximum number of trophoblastic cells to inhibitory levels of MTX during the S-phase of the cell cycle.

Topics: Adult; Drug Administration Schedule; Female; Humans; Hydatidiform Mole; Injections, Intravenous; Leucovorin; Methotrexate; Pregnancy; Pregnancy Complications, Neoplastic; Uterine Neoplasms

Serial radioimmunoassay determinations of serum beta hCG and methotrexate were compared in two patients with nonmetastatic gestational trophoblastic neoplasia (NMGTN) treated with Goldstein's modification of Bagshawe's intermediate-dose methotrexate-citrovorum factor rescue-treatment program. Pretreatment beta hCG levels (mIU/ml) ranged within the outer limits of the 10(3) log level. Following intravenous methotrexate, sharp serum peaks between 10(-6) and 10(-5) M were observed. Plasma disappearance was rapid with a 3 log drop noted within 24 hr to levels incapable of inhibiting DNA synthesis. beta hCG levels manifested a 1 to 1.5 log drop over the 8 days of chemotherapy and complete remission was noted within 5 to 6 weeks of the first dose of methotrexate. No significant clinical or laboratory toxicity was observed. Although cell culture studies show that 100% of cell death can be achieved with serum levels of 10(-5) M in methotrexate-resistant choriocarcinoma, similar data do not exist for previously untreated trophoblastic neoplastic cells. These preliminary observations suggest that serum methotrexate levels are important for establishing sensitivity levels in a heterogeneous population of trophoblastic cells in NMGTN and that the total dose of methotrexate may be safely preselected on the basis of the pretreatment beta hCG.

Topics: Adult; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Peptide Fragments; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms; Vacuum Curettage

Two treatment regimens for nonmetastatic gestational trophoblastic disease are compared in this retrospective study. The course of 39 patients with nonmetastatic gestational trophoblastic disease treated with methotrexate alone is contrasted to that of 29 patients with nonmetastatic gestational trophoblastic disease who were treated with methotrexate alternated with folinic acid. Of those patients initially treated with methotrexate alone, 7.7% developed methotrexate-resistant disease and required a change in chemotherapy for induction of remission. In contrast, 27.5% of patients initially treated with methotrexate and folinic acid developed methotrexate-resistant disease and required a change in chemotherapy to achieve remission. Ultimately, remission was achieved in all patients. Methotrexate as single-agent chemotherapy was found to be consistently more toxic than methotrexate alternated with folinic acid. It is concluded that methotrexate with folinic acid at the dosage used in this study, while less toxic than methotrexate alone, is less effective than methotrexate alone in the induction of remission of nonmetastatic gestational trophoblastic disease.

Topics: Choriocarcinoma; Dactinomycin; Drug Therapy, Combination; Female; Humans; Hydatidiform Mole; Leucovorin; Methotrexate; Pregnancy; Pregnancy Complications; Retrospective Studies; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Choriocarcinoma; Chorionic Gonadotropin; Dactinomycin; Doxorubicin; Drug Therapy, Combination; Female; Humans; Hydatidiform Mole; Infant, Newborn; Leucovorin; Methotrexate; Neoplasm Metastasis; Pregnancy; Uterine Neoplasms; Vincristine

The reproductive performance of 36 women who had been successfully treated for gestational trophoblastic tumors with multiple courses of cytotoxic agents including methotrexate, 6-mercaptopurine, actinomycin D, and 6-azauridine, between 1962 and 1972, has been studied in comparison with 36 patients who had spontaneously aborted a hydatidiform mole but received no treatment and a control group consisting of 36 women attending an antenatal clinic. The majority of patients who wanted further pregnancies following chemotherapy had one or more successful conceptions. The incidence of abnormal pregnancies in the treated group was higher than that of the control group. Similarly, there was a higher number of abnormal pregnancies in the untreated mole patients when compared with the control group. This suggests that patients who develop trophoblastic tumors tend to have a poor obstetric history and that this is not significantly worsened by chemotherapy.

Topics: Abnormalities, Drug-Induced; Antineoplastic Agents; Azauridine; Child; Child, Preschool; Dactinomycin; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hydatidiform Mole; Infant; Infant, Newborn; Leucovorin; Male; Mercaptopurine; Methotrexate; Pregnancy; Pregnancy Complications; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Choriocarcinoma; Cyclophosphamide; Dactinomycin; Estrogens; Female; Humans; Hydatidiform Mole; Leucovorin; Male; Methotrexate; Neoplasm Metastasis; Pregnancy; Testosterone; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

Topics: Antineoplastic Agents; Choriocarcinoma; Female; Humans; Hydatidiform Mole; Hydroxypropiophenone; Leiomyoma; Leucovorin; Methotrexate; Pregnancy; Pregnancy Complications

Topics: Angiography; Catheterization; Choriocarcinoma; Chorionic Gonadotropin; Drug Therapy; Female; Femoral Artery; Gonadotropins; Humans; Hydatidiform Mole; Hysterectomy; Injections, Intramuscular; Leucovorin; Methotrexate; Pelvic Neoplasms; Perfusion; Pregnancy; Prognosis; Trophoblastic Neoplasms; Urine; Uterine Neoplasms