levoleucovorin and Uterine-Neoplasms

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 diseases comprise a rare spectrum of disorders in which the normal regulatory mechanisms controlling the behaviour of trophoblastic tissue are lost. They vary from the benign complete and partial hydatidiform moles to the frankly malignant choriocarcinoma and placental site trophoblastic tumours. The majority will be cured by suction curettage, followed by human chorionic gonadotrophin screening, but some will go on to need chemotherapy. The majority of patients will be cured even despite the presence of metastatic disease. Patients should have their treatment stratified according to various prognostic factors in order to ensure firstly their disease is eliminated and secondly to reduce the incidence of long-term treatment complications.

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

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dactinomycin; Female; Humans; Hydatidiform Mole, Invasive; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Pregnancy; Uterine Neoplasms; Vincristine

Single-agent chemotherapy for nonmetastatic gestational trophoblastic disease is most successful for patients who have had an antecedent molar pregnancy with a plateau or persistent beta-human chorionic gonadotropin elevation after molar evacuation. Traditionally, single-agent, five-day, intramuscular methotrexate has been associated with high cure rates, as has methotrexate with citrovorum factor rescue, which reduces toxicity. Standard definitions of low-risk gestational trophoblastic disease and response assessment are critical to a comparison of prognostic features related to single-agent therapy success. Methotrexate with folinic acid rescue administered as primary therapy does achieve an excellent therapeutic outcome with limited chemotherapy exposure but at increased cost. The weekly intramuscular methotrexate Gynecologic Oncology Group (GOG) regimen is inexpensive and allows close monitoring of disease status. Single-dose or pulsed actinomycin-D provides a high level of complete response, although gastrointestinal toxicity, mainly nausea and vomiting, is quite common. Management of first-line chemotherapy failures is unclear, although in the GOG methotrexate trial it was evident that another agent, such as actinomycin-D, should be used to provide the highest success rate. The use of a single agent in low-risk metastatic trophoblastic disease (lung and/or vaginal metastases) depends upon restricting it to patients who have not failed prior chemotherapy, have a low World Health Organization score and have no evidence of the presence of choriocarcinoma, but a much higher first-line failure rate should be anticipated than in nonmetastatic disease. Other single-agent regimens have been proposed that are worthy of investigation to create a safer, more efficacious and more convenient regimen for low-risk gestational trophoblastic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Clinical Protocols; Clinical Trials as Topic; Combined Modality Therapy; Dactinomycin; Drug Administration Schedule; Drug Costs; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Leucovorin; Methotrexate; Neoplasm Staging; Peptide Fragments; Pregnancy; Prognosis; Risk Factors; Treatment Failure; Trophoblastic Neoplasms; Uterine Neoplasms; Vacuum Extraction, Obstetrical

Eighty patients with low-risk and 5 patients with intermediate-risk gestational trophoblastic neoplasia (GTN) (WHO classification) were treated with single-agent high-dose methotrexate with folinic acid rescue (MTX/FAR). By the NCI classification, 65 patients had nonmetastatic GTN, 13 patients had low-risk metastatic GTN, and 7 patients had high-risk metastatic GTN. Seventy-one (84%) patients achieved remission (beta HCG < or = 5 IU/liter) with MTX/FAR, whereas 14 (16%) failed to achieve remission with MTX/FAR alone. All failures were salvaged with second-line therapies. Patients successfully treated with MTX/FAR required a median of 4 courses to achieve remission, and a median of 2 consolidative courses. Factors found predictive of failure with MTX/FAR were pretreatment beta HCG (P = 0.003), prior history of GTN (P < 0.04), and time from termination of antecedent pregnancy to initiation of treatment (P < 0.05). No significant difference was noted between the "success" and "failure" groups with respect to MTX dose or infusion time, the timing and dosage of folinic acid rescue, the number of courses of MTX, or the mean interval between courses. Multivariate analysis revealed that the pretreatment beta HCG (P < 0.01) and short time from termination of antecedent pregnancy to initiation of treatment (P < 0.03) were independently significant for failure. No significant (grade 3/4) hematologic or gastrointestinal toxicity occurred, and no treatment delays or dose reductions were required. This regimen is both effective and well tolerated; however, the theoretical advantages of high-dose methotrexate do not appear to offer any clinical advantage over conventional dose MTX in low- and intermediate-risk GTN.

Topics: Biomarkers, Tumor; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Drug Administration Schedule; Female; Humans; Leucovorin; Methotrexate; Peptide Fragments; Pregnancy; Remission Induction; Treatment Outcome; Trophoblastic Neoplasms; Uterine Neoplasms

The efficacy of single agent chemotherapy with methotrexate in low risk gestational trophoblastic disease is well established, but efforts to reduce toxicity and patient time and cost continue. Twenty-five patients with nonmetastatic postmolar gestational trophoblastic disease were seen by the Division of Gynecologic Oncology at the University of South Florida between February 1986 and December 1991. Patients were treated with either weekly intramuscular methotrexate 40 mg/M2 (Group 1, n = 13) or alternating doses of intramuscular methotrexate 1 mg/kg and folinic acid 0.1 mg/kg over eight consecutive days with an eight- day interval (Group 2, n = 12). Patient age, body weight and pre-treatment beta-hCG values were similar in the two groups. One patient defaulted from treatment and was lost to follow-up. All other patients were cured. Complete remission was achieved with primary chemotherapy in nine (69%) patients in Group 1 and nine (75%) in Group 2. All patients with pre-treatment beta-hCG of 650 mIU/ml or less responded to primary therapy whereas 50% of those with higher levels required second-line therapy. When secondary and tertiary treatment were included, the duration of treatment was similar in both groups. Remission was achieved at significantly lower levels of methotrexate in group 1 patients (p < 0.001). No major toxicities occurred. Side effects were gastrointestinal and myelosuppressive and occurred in 2.5% and 15.6% of treatment cycles in Groups 1 and 2, respectively (p < 0.01). Weekly methotrexate is an equally effective and less toxic regimen than eight-day methotrexate-folinic acid in nonmetastatic postmolar gestational trophoblastic disease.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Dactinomycin; Drug Administration Schedule; Female; Humans; Leucovorin; Methotrexate; Peptide Fragments; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

The clinical course of 48 patients with low-risk metastatic gestational trophoblastic tumors (GTTs) treated with primary single-agent chemotherapy was reviewed. All patients achieved sustained remission, although 25 (51%) required a second single-agent regimen, and 7 (14%) needed combination chemotherapy to achieve it. An average of 3.4 courses of chemotherapy were necessary to achieve remission, and 6 patients (12%) underwent resection of resistant tumor foci. Primary single-agent chemotherapy is a reasonable treatment option in patients with low-risk metastatic GTT.

Topics: Aspartate Aminotransferases; Dactinomycin; Female; Granulocytes; Humans; Leucovorin; Methotrexate; Neoplasm Metastasis; Platelet Count; Pregnancy; Prognosis; Remission Induction; Trophoblastic Neoplasms; Uterine Neoplasms

In 1981, the Gynecologic Oncology Group initiated a prospective randomized study in which patients with poor-prognosis gestational trophoblastic disease received either standard MAC chemotherapy (methotrexate, dactinomycin, and chlorambucil) or the modified CHAMOMA regimen (methotrexate, dactinomycin, cyclophosphamide, doxorubicin, melphalan, hydroxyurea, and vincristine). The protocol was closed in May 1986 because the modified CHAMOMA regimen was significantly more toxic and possibly less effective. There were 42 patients entered, with 22 receiving MAC and 20 receiving modified CHAMOMA. There have been six deaths due to disease in the modified CHAMOMA group and none in the MAC group. Five MAC failures and one modified CHAMOMA failure have been rescued by surgery and/or chemotherapy. All six of the patients who died on the modified CHAMOMA regimen had developed disease following a previous term pregnancy, but none had prior chemotherapy. All seven patients who were treated for gestational trophoblastic disease after term pregnancy in the MAC group were cured of disease. With the modified CHAMOMA regimen, 44% of patients had life-threatening hematologic toxicity, as compared with only 9% of the MAC patients. Thus, the standard MAC regimen appears to be at least equally effective and much less toxic than the modified CHAMOMA regimen, indicating a more favorable therapeutic index.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chlorambucil; Cyclophosphamide; Dactinomycin; Doxorubicin; Female; Humans; Hydroxyurea; Leucovorin; Methotrexate; Multicenter Studies as Topic; Pregnancy; Prospective Studies; Random Allocation; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

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.
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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

The authors report a case with spontaneous renal hemorrhage caused by invasive mole. The diagnosis was gestational trophoblastic disease (GTD), with metastasis to brain, kidneys, and lungs at Stage IV. The patient was given etoposide-methotrexate-actinomycin D plus cyclophosphamide-vincristine (EMACO) treatment regimen for 11 times including three times with consolidation chemotherapies. Laparoscopically-assisted vaginal hysterectomy (LAVH) + laparoscopic-assisted left renal excision + evacuation of the left perirenal hematoma were performed during the eighth chemotherapy.. Post-operational pathological examination revealed trophoblasts within the lesions present in uterine fundus and the residue images of a few trophoblasts present in the left renal mass.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Dactinomycin; Doxorubicin; Etoposide; Female; Hemorrhage; Humans; Hydatidiform Mole, Invasive; Kidney Diseases; Leucovorin; Methotrexate; Pregnancy; Uterine Neoplasms; Vincristine

To assess prognosis of gestational trophoblastic neoplasia (GTN) and obstetric outcome after chemotherapy.. Sixty-six patients had diagnosis of hydatiform mole on curettage and 18 developed GTN. Two patients were referred with pathological diagnosis of GTN. Chemotherapy was tailored according to International Federation of Gynecology and Obstetrics risk scoring system.. All patients with GTN but one, were recovered by chemotherapy and had no evidence of disease after a median follow-up of 80 months. Only the patient with epithelioid trophoblastic tumor died of disease. Seven out of the eight women who tried to conceive after chemotherapy became pregnant. Ten conceptions occurred, resulting in no molar pregnancy, three miscarriages and seven term-live healthy births (70.0%). All seven babies showed normal development and growth after a median follow-up of 38 months.. The prognosis of women with GTN is very good, and obstetric outcomes of those who conceive after chemotherapy are similar to those of the general population.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin, beta Subunit, Human; Dactinomycin; Etoposide; Female; Fertility Preservation; Gestational Trophoblastic Disease; Humans; Leucovorin; Methotrexate; Middle Aged; Pregnancy; Prognosis; Term Birth; Treatment Outcome; Uterine Neoplasms; 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

Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Dactinomycin; Doxorubicin; Etoposide; Female; Humans; Leucovorin; Methotrexate; Neoplasm Metastasis; Pregnancy; Uterine Neoplasms; Vincristine

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Etoposide; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Prenatal Diagnosis; Tomography, X-Ray Computed; Uterine Neoplasms; Vincristine

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

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Dactinomycin; Doxorubicin; Endometrium; Etoposide; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Pregnancy; Uterine Neoplasms; Vincristine

Uterine choriocarcinoma developing in patients beyond reproductive age is a rare occurrence. We report a case of choriocarcinoma of uterine corpus in a 54-yr-old woman after 7 yr of menopause and 25 yr after last child birth. She presented with pain in the abdomen, and on radiological investigation a left uterine adnexal mass of 3.4 x 2.8 cm size was detected. Her serum CA125 level was 40 mIU/mL (normal up to 35 mIU/mL). Hysterectomy revealed an intramural growth in left uterine cornu measuring 3.5 x 3.0 x 2.5 cm. Histological features of the tumor were consistent with choriocarcinoma, and immunohistochemistry detected strong reactivity for beta-hCG in the tumor cells. Serum beta-hCG level 4 wk after surgery was 1345 mIU/mL. The patient was put on combination chemotherapy (EMACO). She achieved serological remission but showed a rise in serum beta-hCG level 4 wk after completion of chemotherapy. We conclude that a high level of suspicion may help in preoperative diagnosis of uterine choriocarcinoma in the postmenopausal age group. However, the response to chemotherapy in these cases may not be as encouraging as in choriocarcinoma of reproductive age.

Topics: Antineoplastic Combined Chemotherapy Protocols; CA-125 Antigen; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Combined Modality Therapy; Dactinomycin; Doxorubicin; Etoposide; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Postmenopause; Uterine Neoplasms; Vincristine

To study the incidence of postmolar gestational trophoblastic disease (GTD) following hydatidiform mole and to evaluate the effectiveness of single-agent chemotherapy using methotrexate with folinic acid rescue.. A prospective study of all cases of hydatidiform mole diagnosed and treated in the department of obstetrics and gynecology, Medical College, Calicut, India, was started in June 1990 to determine the incidence of postmolar GTD and the effectiveness of single-agent chemotherapy with methotrexate and folinic acid in postmolar nonmetastatic GTD.. For the 15-year period from June 1990 to May 2005, 1,569 cases of hydatidiform mole were diagnosed and managed at our institution. The incidence of postmolar GTD among 1,569 cases of hydatidiform mole was 20.4%. Of the 321 cases of postmolar GTD diagnosed, 284 patients (88.5%) achieved complete remission with the methotrexate/folinic acid regimen. Fourteen multiparous patients (4.4%) underwent hysterectomy with methotrexate/folinic acid and achieved remission. Thus, 92.9% of patients with postmolar GTD had complete remission with the methotrexate/folinic acid regimen. The rest of the cases required multiagent therapy.. Regular follow-up of patients after evacuation of hydatidiform mole will detect cases of postmolar GTD at an early stage. Single-agent chemotherapy with methotrexate was effective in 92.9% of our cases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Gestational Trophoblastic Disease; Humans; Incidence; India; Leucovorin; Methotrexate; Pregnancy; Prospective Studies; Puerperal Disorders; Treatment Outcome; Uterine Neoplasms

Non-Hodgkin's Lymphomas (NHL) frequently affect the uterine corpus, cervix, and vagina in cases of advanced disease. However, these organs are rarely the site of origin of this type of neoplasia. Because of the rarity of primary genital tract lymphomas, a standard treatment has not been defined.. Three patients with large B-cell primary Non-Hodgkin's lymphoma of the lower genital tract (vaginal, cervical and cervico-vaginal) presented with bulky lesions and underwent diagnostic evaluation, staging, and chemotherapy with adriamycin-containing regimens. All three patients, including two with stage IIE and one with stage IE disease demonstrated complete remission and are alive and well without evidence of disease at 10, 7, and 6 years of follow-up, respectively.. Our observations suggest that young patients with large B-cell lymphomas of lower genital tract stages I-IIE, even with bulky lesions, may benefit from chemotherapy alone as initial treatment.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Methotrexate; Neoplasm Staging; Prednisone; Uterine Cervical Neoplasms; Uterine Neoplasms; Vaginal Neoplasms; Vincristine

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Drug Resistance, Neoplasm; Female; Humans; Leucovorin; Methotrexate; Neoplasm Staging; Pregnancy; Terminology as Topic; Trophoblastic Neoplasms; Uterine Neoplasms

The aim of the present study was to establish the accurate cutoff points of post-treatment serum beta-hCG values in identifying chemotherapeutic refractory cases among patients with low-risk persistent trophoblastic disease (PTD) treated with 8-day methotrexate-folinic acid as the primary therapy.. The values of serum beta-hCG measured before initiating treatment and weekly thereafter in 26 patients with low-risk PTD undergoing 8-day methotrexate-folinic acid treatment were analyzed. Thereafter, we determined the weekly cutoff points to identify the patient refractory for treatment by means of receiver-operating characteristic (ROC) plots analysis.. The values of cutoff points in the pretreatment, the post-treatment 1st, 2nd, 3rd, and 4th week were 18.6, 15.0, 5.4, 3.4, and 2.0 ng/ml, respectively, and the value of accuracy during these weeks was appropriate (> 80%). When using the cutoff points of one and two weeks after initiating treatment, the accuracy in identifying chemotherapeutic refractory patients was 87.5% and 88.0%, respectively, with the highest values exceeding 85%. The sensitivity and specificity at one week were 92.9 and 80.0%, respectively. Similarly, the sensitivity and specificity at two weeks were 93.3 and 80.0%, respectively.. These results suggest that the cutoff points of one and two weeks after initiating treatment are useful in identifying chemotherapeutic refractory patients among low-risk PTD patients, receiving 8-day methotrexate-folinic acid treatment.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chorionic Gonadotropin; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Pregnancy; Reference Values; Sensitivity and Specificity; Treatment Outcome; Trophoblastic Neoplasms; Uterine Neoplasms

Choriocarcinoma are malignant neoplastic tumors from the trophoblastic tissue with a tendency to early metastases. Beside pulmonary metastases there are often cerebral metastases, leading to intracerebral hemorrhage often responsible for the first clinical symptoms. In young women, symptoms like vaginal or pulmonary bleeding or neurologic disturbances shortly after a hydatiform mole or a normal pregnancy, accompanied by high levels of HCG in serum and CSF, choriocarcinoma should be considered. Choriocarcinoma are very sensitive to chemotherapy, which consists--depending on the stage of the disease--of a mono- or polychemotherapy. Cure rates are high, even in extended stages with cerebral metastases--as in the case described. Brain metastases with or without oncotic aneurysms can be rapidly controlled by immediate whole brain irradiation. Surgical interventions may be necessary in the case of life threatening bleedings. Levels of HCG in serum and cerebrospinal fluid are good markers to control the effect of therapy. But--as shown in this patient--levels of HCG in CSF may decrease protracted without affecting prognosis. Oncotic aneurysms are rarely reported and mostly detected post mortem. The presented case leads to a more optimistic attitude and demonstrates efficacy of immediately started radio- and chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Blindness; Brain Neoplasms; Cerebral Angiography; Choriocarcinoma; Chorionic Gonadotropin; Combined Modality Therapy; Dactinomycin; Doxorubicin; Etoposide; Female; Follow-Up Studies; Humans; Intracranial Aneurysm; Leucovorin; Methotrexate; Pregnancy; Prognosis; Radiotherapy Dosage; Time Factors; Tomography, X-Ray Computed; Uterine Neoplasms; Vincristine

A case of epithelioid trophoblastic tumour (ETT), occurring in a fallopian tube of a 39-year-old woman, is reported. The patient presented with a positive pregnancy test, but continued to have 'periods'. A palpable right adnexal mass was noted that was confirmed on ultrasound. The mass was removed together with the uterus, omentum and associated ovary. Careful examination of the uterus revealed no evidence of either an antecedent tumour or intra-uterine pregnancy. Histologically, the tubal mass displayed sheets and islands of large, relatively uniform, mitotically active polyhedral cells, with surrounding necrosis. The immunoprofile of the tumour was atypical in that alpha-inhibin and epidermal growth factor were weakly positive, but other results were consistent with the diagnosis of ETT. The patient received a foreshortened course of standard EMACO (etoposide, actinomycin-D, methotrexate, vincristine, and cyclophosphamide) combination chemotherapy for high-risk gestational trophoblastic disease. Serum beta-hCG fell from a pre-operative level of 52 000 U/mL to non-pregnant levels within two courses and she remains well and disease-free 12 months post-diagnosis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chorionic Gonadotropin, beta Subunit, Human; Dactinomycin; Disease-Free Survival; Doxorubicin; Epidermal Growth Factor; Epithelioid Cells; Etoposide; Fallopian Tube Neoplasms; Female; Humans; Hysterectomy; Immunohistochemistry; Inhibins; Leucovorin; Methotrexate; Pregnancy; Treatment Outcome; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

Gestational trophoblastic diseases (GTD) represent a group of malignancies classified as invasive mole, choriocarcinoma, and placental-site trophoblastic tumors. The overall cure rate in the treatment of this malignant disorder now exceeds 90%. The aim of this study is retrospectively to evaluate the clinical characteristics and effectiveness of single-agent chemotherapy (CT) and combination chemotherapy according to the World Health Organization (WHO) risk groups of gestational trophoblastic diseases. Thirty one patients with GTD were treated in our institute between 1990-1998. Median age at presentation was 29 years (range 19-70 years). All patients were classified with respect to the WHO scoring system. According to this system, patients were divided into three clinical groups: low-risk nonmetastatic (low-risk group with good prognosis), low-risk metastatic, and high-risk metastatic (high risk group with poor prognosis). Eighteen patients in the nonmetastatic low-risk group with favorable prognostic factors received single agent CT (methotrexate and folinic acid), while 3 patients with metastatic low-risk and 10 patients in the metastatic high-risk group with poor prognosis received combination CT (EMA-CO). Complete response (CR) was obtained in all patients in the low risk group with good prognosis, whereas 9/13 (69%) patients in the poor prognosis group achieved CR and 4 (31%) had partial responses. This clinical classification system may be currently prefer for determining initial therapy in women with malignant gestational trophoblastic tumors. And, our report confirms that the alternating EMA/CO regimen is a well-tolerated and effective combination for the treatment of women with high-risk GTD.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Etoposide; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Pregnancy; Pregnancy Complications, Neoplastic; Prognosis; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

We have simplified the treatment of gestational trophoblastic disease (GTD) in order to reduce the number of patients exposed to potentially carcinogenic chemotherapy. Patients who score 0 to 8 on the Charing Cross scoring system are classified as low-risk and receive methotrexate (MTX) and folinic acid (FA), whereas those who score higher than 8 are classified as high-risk and receive the etoposide, methotrexate, and dactinomycin (EMA)/cyclophosphamide and vincristine (CO) regimen.. Between 1992 and 2000, 485 women with GTD were commenced on MTX/FA at Charing Cross Hospital, London, United Kingdom. If patients developed MTX resistance or toxicity, treatment was altered according to the level of beta human chorionic gonadotropin (hCG). If serum hCG was < or = 100 IU/L, patients received dactinomycin; if hCG was greater than 100 IU/L, patients received EMA/CO.. The median duration of follow-up was 4.7 years. Overall survival was 100% and the relapse rate was 3.3% (16 of 485 patients). hCG values normalized in 324 (66.8%) of 485 patients with MTX alone, whereas 161 (33.2%) of 485 patients required a change in treatment, 11 because of MTX toxicity and 150 because of MTX resistance. Sixty-seven patients changed to dactinomycin, of whom 58 achieved normal hCG values, and nine required third-line chemotherapy with EMA/CO. hCG values normalized in 93 (98.9%) of 94 patients who changed directly to EMA/CO from MTX.. Single-agent dactinomycin has activity in patients with low-risk GTD who develop MTX resistance and whose hCG is low. Simplifying the stratification of GTD into two classes (low- and high-risk) does not compromise overall outcome and may reduce the risk of second tumors.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Clinical Protocols; Cyclophosphamide; Dactinomycin; Drug Administration Schedule; Etoposide; Female; Follow-Up Studies; Humans; Leucovorin; Methotrexate; Pregnancy; Risk; Survival Analysis; Treatment Outcome; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

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

The objective of this study was to determine the complete response rate to weekly intravenous methotrexate at 100 mg/m(2) with folinic acid for patients with nonmetastatic gestational trophoblastic neoplasia.. From 1988 to 1999, 22 women with nonmetastatic gestational trophoblastic neoplasia were treated with weekly intravenous methotrexate with folinic acid at the Hamilton Regional Cancer Centre. Complete response was defined as the attainment of a serum beta-hCG level <5 IU/L for 3 consecutive weeks. Toxicity was graded according to the National Cancer Institute of Canada-Clinical Trials Group criteria for chemotherapy toxicity.. There were 10 women who achieved complete response with weekly intravenous methotrexate alone (45.5%). Of the 12 who did not achieve complete response with methotrexate, 10 received actinomycin D and 2 received EMA as second-line chemotherapy. Patients successfully treated with methotrexate required a median of 6.5 cycles (including 2 cycles for consolidation) to achieve complete response. The only significant prognostic factor for failure with methotrexate was pretreatment beta-hCG (P = 0.01).. Only a select group of patients with low pretreatment beta-hCG titers would be expected to achieve complete response with this regimen. Large randomized studies are required to determine the optimal treatment for nonmetastatic gestational trophoblastic neoplasia.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin, beta Subunit, Human; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Leucovorin; Methotrexate; Pregnancy; Retrospective Studies; Trophoblastic Neoplasms; 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

In the UK there are standardized surveillance procedures for gestational trophoblastic disease. However, there are differences in practice between the two treatment centres in terms of definition of persistent gestational trophoblastic disease, prognostic risk assessment and chemotherapeutic regimens. The role of prophylactic chemotherapy for cerebral micrometastatic disease in persistent gestational trophoblastic disease is unclear. We have analysed the outcome of 69 patients with lung metastases who elsewhere might have received prophylactic intrathecal chemotherapy. Of the 69 patients, 67 received intravenous chemotherapy only. The other two patients had cerebral metastases at presentation. One patient who received only intravenous chemotherapy subsequently developed a cerebral metastasis, but this patient's initial treatment was compromised by non-compliance. This experience supports our current policy of not treating patients with pulmonary metastases, without clinical evidence of central nervous system (CNS) involvement, with prophylactic intrathecal therapy.

Topics: Adolescent; Adult; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Dactinomycin; Etoposide; Female; Follow-Up Studies; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Patient Compliance; Pregnancy; Prognosis; Retrospective Studies; Risk Assessment; Trophoblastic Neoplasms; Uterine Neoplasms

Post-partum choriocarcinoma is a rare complication of pregnancy. We have analysed a series of nine consecutive patients presenting with choriocarcinoma after a full-term non-molar pregnancy. All patients were managed at the Supraregional Trophoblastic Disease Screening and Treatment Centre at Weston Park Hospital, Sheffield between 1987 and 1996. All presented with persistent primary or secondary post-partum haemorrhage. Treatment with multiagent chemotherapy (initially methotrexate, dactinomycin and etoposide) was successful in all cases. Early diagnosis is important because this rare condition is potentially curable with appropriate chemotherapy.

Topics: Adult; Antidotes; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Etoposide; Female; Humans; Leucovorin; Methotrexate; Postpartum Hemorrhage; Postpartum Period; Pregnancy; Retrospective Studies; Uterine Neoplasms; Vincristine

Methotrexate (MTX) is a folate antagonist widely used both as an anticancer drug and as an immunosupressant. Administration of an 8-day methotrexate and folinic acid regime may be associated with pleuritic chest pain and pneumonitis. We have reviewed the toxicity seen in 168 consecutive patients treated with low-dose MTX for persistent trophoblastic disease. Twenty-five per cent of patients developed serosal symptoms, pleurisy was the commonest complaint. The majority of patients had mild to moderate symptoms which were controlled with simple analgesia and did not necessitate a change in treatment; 11.9% had severe symptoms which necessitated a change in treatment. One patient developed a pericardial effusion and a second patient developed severe reversible peritoneal irritation. The possible aetiology and pathophysiology of methotrexate-induced serosal toxicity is discussed.

Topics: Adult; Antimetabolites, Antineoplastic; Female; Humans; Leucovorin; Methotrexate; Pericarditis; Peritonitis; Pleurisy; Pregnancy; Serositis; Trophoblastic Neoplasms; Uterine Neoplasms

To analyze the causes of therapeutic success and failure in the management of patients with high-risk gestational trophoblastic tumors (GTTs).. Analysis of 272 consecutive high-risk patients treated at the trophoblastic disease center at the Charing Cross Hospital between 1979 and 1995.. EMA (etoposide, methotrexate, actinomycin D)/CO (cyclophosphamide, vincristine) chemotherapy is our treatment of choice for patients with high-risk GTT. In 272 consecutive patients the cumulative five-year survival was 86.2% (95% confidence interval, 81.9-90.5%). No deaths occurred from GTT more than two years after the start of treatment. In patients whose disease became resistant to EMA/CO or relapsed after receiving EMA/CO, the majority (70%) could be salvaged with further chemotherapy (usually with the EP (etoposide, cisplatin)/EMA chemotherapy with or without surgery. Multivariate analysis identified the following adverse prognostic factors: presence of liver metastases (P < .0001), prolonged interval from antecedent pregnancy (P < .0001), presence of brain metastases (P = .0008) and term delivery of antecedent pregnancy (P = .045). Intensive chemotherapy for treating high-risk GTT carries a small risk of inducing second malignancies, and two patients developed acute myeloid leukemia, 2 cervical malignancy and 1 gastric adenocarcinoma after receiving EMA/CO chemotherapy.. EMA/CO is an effective and well-tolerated regimen for high-risk GTT. Salvage chemotherapy with EP/EMA is effective in the majority of patients whose disease is resistant to EMA/CO and should be combined with surgery when the dominant site of resistant disease is known. Major adverse prognostic variables have been identified, and patients with combinations of these factors should be considered for innovative therapeutic approaches from the outset.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Drug Resistance, Neoplasm; Etoposide; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Risk Factors; Treatment Outcome; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

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

Cutaneous metastases of gestational trophoblastic disease are extremely uncommon. A patient with metastatic, poor prognosis disease and a large metastatic lesion on her left fifth digit is presented. The clinical course and complete response to EMACO chemotherapy are outlined. The presence of metastatic disease in a reproductive-age woman requires consideration of gestational trophoblastic disease in the differential diagnosis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Dactinomycin; Diagnosis, Differential; Doxorubicin; Etoposide; Female; Fingers; Humans; Leucovorin; Methotrexate; Pregnancy; Pregnancy Complications, Neoplastic; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

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

The authors report their 12 years of experience of intra arterial chemotherapy in pelvic recurrences and inoperable advanced stages of uterine carcinoma, rectal cancer and anal cancer. In squamous cell cancers the drug associations were mitomycin C, bleomycin, fluorouracil and folinic acid and cisplatin. In adenocarcinoma the same protocol contained no bleomycin. Drugs were infused for a 48 hours period in continuous infusion. The dosages were the same than in the intravenous regimens. Twenty patients with pelvic recurrences were included in this retrospective study: six were uterine cancers, fourteen were colo rectal cancers and two had advanced stage uterine cancer. Pain decreased in 10/14 patients with ano-rectal cancer pre sacral recurrence. Partial response was observed in 12 patients. Complete secondary surgical resection was possible in 4/14 rectal cancers and 6/6 uterine cancer recurrences. Chemotherapy induced a pathological complete response in 4/6 uterine cervix carcinoma recurrences. These observations led to perform pelvic intra arterial chemotherapy as first line treatment of locally-advanced inoperable pelvic tumors: 11 uterine cancers and five ano-rectal cancers. The objective were: tumor reduction before radiotherapy or surgery, tumor sterilization, decrease tumor volume for better radiation dosimetry, increase the chance of organ-preservation. The observation of tumor reduction in this small number of patients does not allow to draw definite conclusions. However the introduction of intra arterial pelvic chemotherapy as first line treatment of inoperable pelvic cancer warrants further studies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Bleomycin; Cisplatin; Drug Administration Schedule; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Leucovorin; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Rectal Neoplasms; 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

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Etoposide; Female; Humans; Hypertension, Pulmonary; Leucovorin; Methotrexate; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

The value of magnetic resonance imaging (MRI) was studied in a case of a gestational trophoblastic tumour. In addition to the tumour size, MRI made it possible to measure necrotic areas, which are assumed to be a sign of response to chemotherapy. Moreover, uterine zonal anatomy and subserosal uterine veins yielded important information on tumour biology. Complete remission was induced in high-risk patients by etoposide, methotrexate, and actinomycin D treatment.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Dactinomycin; Etoposide; Female; Follow-Up Studies; Humans; Leucovorin; Magnetic Resonance Imaging; Methotrexate; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms; Uterus

Thirty-nine patients with choriocarcinoma and one with post molar trophoblastic tumour are presented. It was often found that there had been a long interval between the preceding pregnancy and the time of diagnosis or presentation. As a result, there was a high incidence of non-gynaecological presenting symptoms and 95 pc of our patients belonged to the high risk or poor prognosis group. The highest rate of cerebral metastases from choriocarcinoma so far reported in the world literature is presented here. At the beginning of 1987, a modified EMA regimen as introduced and has produced a great improvement in survival. The mortality from choriocarcinoma in Harare from 1985 to 1986 was 81 pc. In 1987 to 1988, this has fallen to 31 pc. The follow-up for the patients on the modified EMA regimen varies from four to twenty-four months.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cause of Death; Choriocarcinoma; Dactinomycin; Etoposide; Female; Hospitals, Urban; Humans; Leucovorin; Methotrexate; Pregnancy; Prospective Studies; Retrospective Studies; Survival Analysis; Uterine Neoplasms; Zimbabwe

Choriocarcinoma is a rare malignancy in Scandinavia. We present a case of a young primigravida who experienced an uneventful pregnancy and gave birth to a healthy baby. Six days after delivery she underwent neurosurgery for intracranial hemorrhage. Pathological examination of the evacuated hematoma revealed metastatic choriocarcinoma. Further work-up exposed additional metastases in the lungs and liver. The initial serum level of human chorionic gonadotropin (beta-HCG) was 350,000 IU/I. Chemotherapy was given both intravenously and intrathecally. At 10 weeks, beta-HCG had returned to normal. Treatment was continued for another 10 weeks. Two years after cessation of therapy the patient is still in complete remission. In the discussion we review a scoring system to be used in selecting the mode of treatment, and briefly mention diagnosis and prognosis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Choriocarcinoma; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Cyclophosphamide; Dactinomycin; Female; Humans; Leucovorin; Methotrexate; Peptide Fragments; Pregnancy; Sweden; Uterine Neoplasms

Thirty-two patients with nonmetastatic gestational trophoblastic tumors were treated with methotrexate infusion and folinic acid and the results of this therapy were compared to our prior experience with the 8-day methotrexate-folinic acid regimen. Complete remission was achieved in 22 of 32 (68.7%) patients treated with methotrexate infusion and 147 of 163 (90.2%) patients treated with the 8-day regimen (P less than 0.01). One course of chemotherapy induced complete remission in 19 (86.3%) patients treated with methotrexate infusion and 121 (82.2%) patients treated with the 8-day regimen. All 10 patients resistant to methotrexate infusion later achieved remission with other chemotherapy. Following methotrexate infusion, no patient developed myelosuppression, hepatotoxicity, or alopecia. Efforts should continue to identify new chemotherapeutic protocols that maximize remission rates and minimize toxicity and hospitalization.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Female; Humans; Infusions, Intravenous; Leucovorin; Methotrexate; Neoplasm Recurrence, Local; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

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

Fifty-seven patients with malignant gestational trophoblastic disease (GTD) were treated by the Gynecologic Oncology Unit of the Tygerberg Hospital, Parowvallei, RSA, between 1977 and 1986. Treatment was primarily with triple chemotherapy (MAC) followed by citrovorum factor. The total remission rate in the 23 patients with high risk malignant GTD was 78.3% but in the 16 patients categorized as poor prognosis metastatic disease the remission rate dropped to 68.8%. The third world background in the majority of our patients, the poor general health, and the language barrier indirectly influenced the management of these patients. Psychological problems were evident in 60.9% of our patients. This often resulted in poor patient compliance which adversely influenced the outcome of the disease.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chlorambucil; Dactinomycin; Female; Humans; Leucovorin; Methotrexate; Patient Compliance; Pregnancy; Remission Induction; Risk Factors; Trophoblastic Neoplasms; Uterine Neoplasms

Advances in the management of gestational trophoblastic tumor have been made during the last three decades. Individualization of the therapy is one of the major advances. A number of risk factors has proved to predict accurately the prognosis of each patient. A few systems were currently in use, but difficult in putting them to practical use in the different geographical areas. At National Taiwan University Hospital from 1965 to 1979, 65 patients treated by chemotherapy were analyzed with respect of various prognostic factors. The score was assigned according to the mortality rate of each item to each prognostic factor, and thus established a scoring system which is suitable for the use in Taiwan. After establishment of our scoring system, 51 patients from 1980 to 1986 were treated according to the system and the appropriate therapeutic regimens. The outcome of these patients and toxicity of the different therapeutic regimens are presented.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Cyclophosphamide; Doxorubicin; Drug Evaluation; Etoposide; Female; Humans; Leucovorin; Leukopenia; Liver; Mercaptopurine; Methotrexate; Middle Aged; Pregnancy; Pregnancy Complications, Neoplastic; Prognosis; Remission Induction; Risk Factors; Taiwan; Trophoblastic Neoplasms; Uterine Neoplasms

Between 1964 and 1986, 487 patients with gestational trophoblastic tumour (GTT) were treated with methotrexate and folinic acid. The patients comprise two groups: between 1964 and 1974, 126 patients were treated but were not systematically stratified using a prognostic score before the start of treatment. These patients formed part of the 317 women who were analysed to identify a number of prognostic variables (Bagshawe 1976). Retrospective analysis of these 126 patients using these prognostic factors showed that in the true low-risk group 85/88 (96%) are alive while 20/22 (91%) of the medium-risk group and only 5/16 (31%) of the high-risk group are alive. Overall the survival was 110/126 (87%) with a minimum follow-up of 14 years. From 1974 all patients were stratified on admission into prognostic groups. Of the true low-risk patients 347/348 survived (99.7%); 13 patients were underscored and treated as low risk when they should have been treated as medium risk, 12 (92%) of these are alive, but nine (69%) needed to change treatment because of drug resistance. While the overall survival in the 1974-1986 group was 359/361 (99%) with a minimum follow-up of 16 months, the survival in all patients (1964-1986) was 469/487 (96%). Although the survival in these patients is excellent it should be noted that 69/348 (20%) low-risk patients had to change treatment because of the development of drug resistance, and a further 23 (6%) needed to change treatment because of drug-induced toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Prognosis; Retrospective Studies; Trophoblastic Neoplasms; Uterine Neoplasms

A few reports have documented overdoses of vincristine sulfate. The present report describes our experience with serious complications of a vincristine overdose in an 18-year-old female who had methotrexate-resistant invasive mole. The patient received VAC therapy as the second line chemotherapy after 2 courses of MTX therapy. In the 6th course of VAC therapy, she was given 5 consecutive daily doses of VCR by mistake. On the 5th day of this VAC therapy, she showed the following toxic symptoms: abdominal pain, lumbago, insomnia, bleeding tendency, absence of motor reflex, leukopenia, and paralytic ileus. These symptoms led to realization of the VCR overdose. Leucovorin calcium administration and supportive treatment were carried out. Although it was difficult to evaluate the efficacy of leucovorin calcium on the vincristine toxic symptoms, she recovered and was discharged on the 36th hospital day.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Dactinomycin; Female; Humans; Hydatidiform Mole, Invasive; Leucovorin; Leukopenia; Paralysis; Parenteral Nutrition, Total; Pregnancy; Uterine Neoplasms; Vincristine

From Jan. 1979 to Nov. 1987, 38 patients with invasive mole and 5 patients of choriocarcinoma were primarily treated with methotrexate and citrovorum factor (MTX-CF) rescue. Thirty-two patients had non-metastatic disease (stage I) and 11 had metastatic disease (stage IIA in 5 cases, stage IIB in 3 cases and stage IIIA in 3 cases). Complete remission was achieved in 28 (87.5%) of 32 patients with non-metastatic disease and in 9 (81.8%) of 11 patients with metastatic disease. Six patients with MTX-CF resistant tumors subsequently achieved complete remission with intravenous infusion of KSM and/or AT 1258. All patients were followed up periodically, 22 of them have been followed up for over 2 years, the longest duration of follow-up being 7 years. Seven of the 14 patients with preserved uterus became pregnant after recovery. All children grew up normally.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Female; Follow-Up Studies; Humans; Hydatidiform Mole, Invasive; Leucovorin; Methotrexate; Middle Aged; Pregnancy; Uterine Neoplasms

Low-risk metastatic gestational trophoblastic disease is highly curable with single-agent chemotherapy. Careful monitoring of the response to therapy is essential so that one can alter treatment when signs of drug resistance occur. Because some low-risk patients require complex chemotherapy and/or surgery before achieving remission, therapy should be directed by experienced clinicians at facilities where appropriate ancillary services are available.

Topics: Antineoplastic Combined Chemotherapy Protocols; Dactinomycin; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Risk Factors; Trophoblastic Neoplasms; Uterine Neoplasms

From January 1976 through December 1985, methotrexate (MTX) with citrovorum factor (CF) was administered as primary treatment to 57 patients with low-risk gestational trophoblastic tumor (GTT); 51 patients were non-metastatic and 6 were metastatic GTT. The median number of courses needed to achieve biochemical remission was two (range, 1-7). Complete remission was attained in 95% of non-metastatic GTT patients with postmolar persistent trophoblastic disease, but when choriocarcinoma was histologically confirmed, this fell to 60%. The cure rate of metastatic GTT patients was only 50%. The overall remission rate with the MTX-CF combination was 84.2%. Toxicity was mild, consisting of myelosuppression and mucositis. Fifteen patients were resistant to MTX-CF, or relapsed subsequently, but they all achieved remission with chemotherapy rescue treatment (VP 16 alone, EMA/CO, CHAMOCA). Two patients required a pulmonary lobectomy. They are all still alive in biochemical remission with a median survival of 54 months. Our experience suggests that drug resistance and relapse rate seem related to a beta-HCG value higher than 10(4), an enlarged uterus with myometrial deep involvement, and a histologically confirmed diagnosis of choriocarcinoma. In conclusion, the MTX-CF combination is effective in postmolar GTT, whereas a different therapeutic approach may be considered for a "special" low-risk group of patients, on the basis of prognostic factors.

Topics: Female; Humans; Leucovorin; Methotrexate; Pregnancy; Risk; Trophoblastic Neoplasms; Uterine Neoplasms

During exposure to methotrexate, cultured human choriocarcinoma (BeWo) cells stop proliferating, enlarge, and undergo a complex differentiative response that resembles in utero development of quiescent syncytiotrophoblasts. In the present work, complete inhibition of proliferation and maximal cell enlargement required exposure to 1 microM methotrexate, whereas colony-forming ability, determined after transfer of cells to drug-free medium, was unaffected over a wide range of concentrations (10(-12)-10(-5) M). BeWo cells were sensitive to the antifolate effects of methotrexate since thymidylate synthase activity and incorporation of [14C]formate into DNA, RNA, and protein were reduced by greater than 90% after short drug exposures, and progression of cells through S phase of the cell cycle was blocked by prolonged drug exposures. When methotrexate was coadministered with hypoxanthine and thymidine or leucovorin, its antiproliferative and differentiative effects were blocked. When methotrexate was coadministered with either hypoxanthine or thymidine, its antiproliferative activity was unaffected, whereas expression of syncytiotrophoblastic markers was blocked in the presence of thymidine but not in the presence of hypoxanthine. Exposure of BeWo cells to fluorodeoxyuridine also stimulated cell enlargement and expression of syncytiotrophoblastic markers, and these effects were blocked by coadministration of thymidine. Thus BeWo cells, which were sensitive to the antifolate effects of methotrexate, were not killed during cytostasis but instead entered a reversible differentiated state, apparently resulting from thymidylate starvation and consequent inhibition of DNA synthesis.

Topics: Cell Differentiation; Cells, Cultured; Choriocarcinoma; DNA; DNA Replication; Female; Humans; Hypoxanthine; Hypoxanthines; Leucovorin; Methotrexate; Pregnancy; Thymidine; Uterine Neoplasms

Methotrexate and folinic acid was administered as primary therapy in 185 patients with gestational trophoblastic disease between 1974 and 1984. Methotrexate and folinic acid induced complete remission in 147 (90.2%) of 163 patients with nonmetastatic disease and in 15 (68.2%) of 22 patients with low-risk metastatic disease. Sustained remission was achieved in 132 (81.5%) patients following only one course of chemotherapy. All patients with methotrexate resistance subsequently achieved remission with Actinomycin D or combination chemotherapy. Methotrexate when administered with folinic acid was associated with granulocytopenia, thrombocytopenia, and hepatotoxicity in 11 (5.9%), 3 (1.6%), and 26 (14.1%) patients, respectively. The human chorionic gonadotropin (hCG) regression curve served as a reliable guide for the administration of chemotherapy and enabled the attainment of a high remission rate while limiting chemotherapy exposure. Methotrexate and folinic acid achieves an excellent therapeutic outcome with limited chemotherapy exposure and effectively limits systemic toxicity.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Female; Humans; Hydatidiform Mole, Invasive; Leucovorin; Methotrexate; Middle Aged; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

Fifty patients with high-risk gestation trophoblastic disease received primary multiagent chemotherapy (CHAMOMA). Forty-one patients (82%) achieved sustained completed biochemical remission. The importance of recognizing the high-risk factors and the effectiveness of primary multiagent chemotherapy are demonstrated.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Dactinomycin; Doxorubicin; Female; Hematopoietic System; Humans; Hydroxyurea; Leucovorin; Methotrexate; Middle Aged; Neoplasm Metastasis; Pregnancy; Risk; Time Factors; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

A case of persistent trophoblastic disease with resistance to chemotherapy is presented. The value of continued and frequent serum hCG measurements in such cases is discussed as well as the indications for performing hysterectomy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Combined Modality Therapy; Cyclophosphamide; Dactinomycin; Etoposide; Female; Humans; Hydatidiform Mole, Invasive; Hysterectomy; Leucovorin; Methotrexate; Pregnancy; Uterine Neoplasms; Vincristine

Five patients with gestational trophoblastic disease whose presenting symptom was hemorrhage from vaginal metastases have been added to our previous report. The clinical features, management, and responses to treatment are outlined. All the patients required suturing of the bleeding lesions under general anesthetic to arrest the hemorrhage. In addition one patient needed selective arterial embolization. This did not compromise the response to chemotherapy. We confirm our previous view that the presence of vaginal metastases should be classified as a high-risk factor and that these patients be treated with multiple agent chemotherapy from the outset.

Topics: Adult; Age Factors; Antineoplastic Combined Chemotherapy Protocols; Curettage; Cyclophosphamide; Dactinomycin; Embolization, Therapeutic; Female; Hemostasis, Surgical; Humans; Leucovorin; Methotrexate; Middle Aged; Parity; Pregnancy; Trophoblastic Neoplasms; Uterine Hemorrhage; Uterine Neoplasms; Vaginal Neoplasms

Thirty-nine women with nonmetastatic gestational trophoblastic disease as determined by conventional staging studies were prospectively evaluated with computed axial tomography (CAT) of the lungs. Sixteen patients (41%) had pulmonary micrometastases detected by CAT, which were not detected by routine chest x-ray. Eight patients (20.5%) had indeterminate scans, and only 15 patients (38%) had negative scans. Eight of 16 patients (50%) with pulmonary micrometastases failed initial therapy with methotrexate-folinic acid rescue while one of eight (12.5%) patients in the indeterminate group and one of 15 (6.7%) patients in the true nonmetastatic group failed initial therapy (P less than .006). All patients who failed methotrexate-folinic acid rescue ultimately achieved prolonged remission with actinomycin D. Time to remission was significantly decreased in patients without evidence of pulmonary micrometastases (P = .03), but the total number of courses of chemotherapy was not significantly different (P = .06). No life-threatening toxicity occurred. Pulmonary micrometastases detected by CAT but not chest x-ray are predictive of an increased risk of methotrexate-folinic acid therapy failure. Computed axial tomography of the lungs identifies a group of patients at high risk for failure of methotrexate-folinic acid rescue, and, therefore, may be indicated for routine staging of patients with otherwise nonmetastatic gestational trophoblastic disease.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Middle Aged; Neoplasm Staging; Pregnancy; Tomography, X-Ray Computed; Trophoblastic Neoplasms; Uterine Neoplasms

From 1971 to 1981, twenty patients with poor-prognosis metastatic gestational trophoblastic neoplasia (GTN) were treated with moderate-dose methotrexate (1 g) and folinic-acid rescue (MD-MTX-FAR) as initial therapy. Seven (35%) were cured with MD-MTX-FAR, and salvage chemotherapy was successful in an additional seven, for a total cure rate of 70%. The ultimate outcome is similar to that reported for MAC triple therapy during this era. Hematologic and mucosal toxicity were negligible and no serious complications were encountered. We now use combination chemotherapy in patients with poor-prognosis GTN as first-line treatment. However, these results suggest that there may be advantages to the incorporation of MD-MTX-FAR in combination regimens in place of low-dose methotrexate, because of reduced toxicity and potential benefits for the prophylaxis and treatment of cerebral metastases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Chlorambucil; Chorionic Gonadotropin; Combined Modality Therapy; Dactinomycin; Female; Humans; Hysterectomy; Leucovorin; Liver Neoplasms; Methotrexate; Pregnancy; Prognosis; Time Factors; Trophoblastic Neoplasms; Uterine Neoplasms; Vinblastine

Thirty-three patients with gestational trophoblastic disease treated with methotrexate alone and 68 similar patients treated with methotrexate and citrovorum factor rescue were analyzed. Both groups showed a comparable sustained biochemical remission rate. The group treated with methotrexate and citrovorum factor however showed a shorter interval to induction of remission (p less than 0.05). Contrary to previous reports, the methotrexate and citrovorum factor regimen failed to protect the patients against the development of hepatic toxicity, the incidence of hepatic toxicity being significantly higher in the group treated with methotrexate and citrovorum factor.

Topics: Adult; Aspartate Aminotransferases; Female; Humans; Leucovorin; Liver; Methotrexate; Middle Aged; Pregnancy; Prognosis; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Adult; Brain Neoplasms; Broad Ligament; Choriocarcinoma; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Pregnancy, Ectopic; Rupture, Spontaneous; Uterine Neoplasms

Two cases are presented where malignant trophoblastic tumour of the uterus was successfully treated with pelvic cytostatic perfusion. Local drug perfusion is suggested as a possibly effective treatment in case systemic chemotherapy fails and the patient wishes to bear a child.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Radiography; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

Plasma methotrexate levels were measured in six patients with nonmetastatic and three patients with "low-risk" metastatic gestational trophoblastic neoplasia who were treated by two different methotrexate regimens. Five patients were treated with 16 cycles consisting of methotrexate, 1 mg/kg (days 1, 3, 5, and 7) followed in 24 hours by citrovorum factor, 0.1 mg/kg (days 2, 4, 6, and 8). Cycles alternated between intravenous and intramuscular administration. Statistical differences in plasma levels were found at 1 and 48 hours between the two routes of administration but probably were not of clinical importance. The plasma levels at the time of citrovorum factor administration were below that necessitating citrovorum factor rescue. Four patients were treated with alternating cycles of intravenous or intramuscular methotrexate, 0.5 mg/kg for 5 consecutive days without citrovorum factor. A total of 15 cycles demonstrated no difference in plasma levels at 1, 12, and 24 hours between intravenous and intramuscular administration. Statistical differences in plasma methotrexate levels were noted between the two methotrexate regimens only with intramuscular administration but were not of clinical importance. The reduced toxicity of the methotrexate-citrovorum factor may be due to the scheduling of the methotrexate and not to the citrovorum factor.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Humans; Leucovorin; Methotrexate; Peptide Fragments; Pregnancy; Trophoblastic Neoplasms; 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

Modified triple chemotherapy (MAC III: methotrexate with citrovorum factor, actinomycin D, and cyclophosphamide) was administered as primary treatment to 14 patients with high-risk metastatic gestational trophoblastic tumors (GTT). Ten (71.4%) patients attained complete remission with 1 to 4 courses of MAC III (mean = 2.7 courses). Three of the remaining patients subsequently achieved remission with the modified Bagshawe regimen or vinblastine, bleomycin, and cis-platinum. Following 38 courses of MAC III, moderate hepatotoxicity (SGOT greater than or equal to 150 U) developed after 1 (2.6%) course. Marked thrombocytopenia (platelets less than 50,000/mm3) and marked granulocytopenia (granulocytes less than 500/mm3) developed after 7 (18.4%) and 19 (50%) of the courses, respectively. Platelet transfusions were administered after 4 (10.5%) courses of MAC III and no patient required granulocyte transfusions. MAC III is an effective alternative treatment for patients with high-risk metastatic GTT.

Topics: Adolescent; Adult; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Chemical and Drug Induced Liver Injury; Chorionic Gonadotropin; Cisplatin; Cyclophosphamide; Dactinomycin; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Neoplasm Metastasis; Pregnancy; Pregnancy Complications, Neoplastic; Risk; Thrombocytopenia; Trophoblastic Neoplasms; Uterine Neoplasms; Vinblastine

Fifty-eight consecutive patients with malignant trophoblastic tumors of gestational origin were treated at the 1st Department of Obstetrics and Gynecology of the University of Milan between 1975 and 1981. Thirty-five (60.3%) of the patients were treated with combined surgery and chemotherapy. Of these, 44.8% had genital surgery, 12% extragenital surgery, and 5.1% had emergency laparotomies. Minor surgery was done to 17.1% of the patients. Five patients (20.8%) with tumors limited to the uterus and treated with chemotherapy only became drug-resistant, whereas 3 patients (9%) later developed lung metastases. All the patients are alive without any clinical signs of the disease. When there were metastatic tumors, the survival of the group first submitted to a "debulking" operation of the primary focus was 80%, and the survival of the group treated only with chemotherapy was 78.5%. Seven cases required extragenital surgery for the indications discussed in detail and because they had measurable HCG. Six of these had thoracotomies and one had a craniotomy. Five of the 6 patients who underwent thoracotomy (83.4%) had a complete remission. Chemotherapy remains the treatment of choice for trophoblastic tumors. Nevertheless, our data confirm that for some cases, mostly in the high risk group, complete eradication cannot be obtained with antitumor agents. Adjuvant surgery of carefully selected patients helps to save some of those who no longer respond to chemotherapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chorionic Gonadotropin; Combined Modality Therapy; Female; Humans; Hysterectomy; Leucovorin; Methotrexate; Middle Aged; Neoplasm Metastasis; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

The Southeastern Regional trophoblastic Disease Center has treated 126 patients with metastatic gestational trophoblastic disease from 1966 through 1979. Sixty-three cases were categorized as having a poor prognosis on the basis of criteria published previously. Since 1976, 18 patients have been treated with a modification of Bagshawe's multiagent chemotherapy protocol. Ten of 18 patients (56%) have achieved sustained remission. Seventy-eight percent of these patients encountered serious myelosuppression (white blood count 1000 cells or fewer) and 39% suffered severe thrombocytopenia (platelet count 50,000 or fewer). There were no deaths related to drug toxicity. The courses of therapy and complications of modified Bagshawe chemotherapy are reviewed.

Topics: Antineoplastic Agents; Cyclophosphamide; Dactinomycin; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hydroxyurea; Leucovorin; Methotrexate; Neoplasm Metastasis; Pregnancy; Prognosis; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

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: Contraception; Dactinomycin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Leucovorin; Methotrexate; Neoplasm Invasiveness; Neoplasm Metastasis; Pregnancy; Prognosis; Trophoblastic Neoplasms; Uterine Neoplasms

Methotrexate with citrovorum rescue (MTX-CF) was administered as primary treatment in 106 patients with gestational trophoblastic disease (GTD). Ninety-six patients (90.6%) achieved complete remission with MTX-CF and 77 of these patients (80.2%) required only one course of MTX-CF to attain remission. MTX-CF induced sustained remission in 89 (94.7%) of 94 patients with nonmetastatic GTD and in seven (59.3%) of 12 patients with low-risk metastatic GTD. Resistance to MTX-CF was more common in patients with disseminated disease and with pretreatment hCG titers greater than or equal to 50,000 milliIU/ml. Following MTX-CF, granulocytopenia, thrombocytopenia and hepatotoxicity was observed in only seven (6.6%), three (2.8%), and ten (9.4%) patients, respectively. MTX-CF should be the preferred primary treatment in nonmetastatic and low-risk metastatic GTD.

Topics: Adolescent; Adult; Agranulocytosis; Chemical and Drug Induced Liver Injury; Dactinomycin; Drug Therapy, Combination; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Neoplasm Metastasis; Pregnancy; Thrombocytopenia; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Antineoplastic Agents; Cyclophosphamide; Dactinomycin; Drug Therapy, Combination; Female; Humans; Hysterectomy; Leucovorin; Methotrexate; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

The comparative systemic toxicity of methotrexate (MTX) with citrovorum factor rescue (CF), MTX alone and actinomycin-D (Act-D) in the treatment of gestational trophoblastic neoplasms (GTN) was evaluated in the present study. Treatment with MTX-CF was associated with only a 4% incidence (1 of 25 patients) of hepatic and/or hematologic toxicity and total absence of either a generalized rash or marked alopecia. In contrast, both MTX alone and Act-D were associated with a 48% incidence (12 of 25 patients) of hepatic and/or hematologic toxicity. Actinomycin-D also induced a generalized rash and marked alopecia in 24% (6 of 25 patients) and 52% (13 of 25 patients) of the patients respectively. We found that MTX-CF is the least toxic single agent chemotherapeutic regimen in the management of GTN.

Topics: Bone Marrow; Dactinomycin; Drug Therapy, Combination; Female; Humans; Leucovorin; Liver; Methotrexate; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

Under the aegis of the Queensland Trophoblastic Tumour Registry, a screening and monitoring programme with the beta-subunit of chorionic gonadotrophin as a marker was adopted in the management of patients with gestational trophoblastic disease. Twenty-six patients had been treated with pulses of methotrexate, followed by folinic acid rescue, up to a total dose of 200 mg of methotrexate in each course; the side effects were minor and infrequent. This regimen was effective in producing biochemical and clinical remission in 18 of 19 patients both with non-metastatic and with metastatic persistent disease; the mean duration of treatment was nine weeks and 19.2 weeks respectively. However, it was effective in only three of seven patients with histologically confirmed choriocarcinoma, which suggests that a more aggressive multidrug regimen should be considered from the outset in this high risk group of patients. Our preliminary data have revealed no permanent effects on subsequent fertility or observable effects on the babies so far studied.

Topics: Choriocarcinoma; Chorionic Gonadotropin; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Leucovorin; Lung Neoplasms; Methotrexate; Peptide Fragments; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Adult; Antineoplastic Agents; Cyclophosphamide; Dactinomycin; Drug Resistance; Drug Therapy, Combination; Female; Humans; Hydroxyurea; Leucovorin; Melphalan; Methotrexate; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms; Vincristine

Fifty-one patients with nonmetastatic gestational trophoblastic neoplasms (NMGTN) were treated with either 4 or 6 mg/kg methotrexate (MTX) and citrovorum factor (CF) rescue to determine if the higher dosage could reduce the number of courses of chemotherapy required to achieve remission. Thirty-six of 41 patients treated with 4 mg/kg MTX achieved complete remission with 1 course of chemotherapy. Increasing the initial dose of MTX to 6 mg/kg in 10 patients did not reduce the need for subsequent courses of chemotherapy but did increase associated toxicity. The rate of fall in the human chorionic gonadotropin (hCG) titer following the initial course of MTX-CF was found to be an accurate predictor of therapeutic response. The need for further chemotherapy may be anticipated if the hCG titer has not fallen by 1 log within 18 days.

Topics: Adolescent; Adult; Chemical and Drug Induced Liver Injury; Chorionic Gonadotropin; Drug Administration Schedule; Drug Therapy, Combination; Female; Hematologic Diseases; Humans; Leucovorin; Liver; Methotrexate; Middle Aged; Pregnancy; Risk; Trophoblastic Neoplasms; Uterine Neoplasms

Thirty-five patients with nometastatic gestational trophoblastic neoplasms and 3 patients with metastatic gestational trophoblastic neoplasms were treated primarily with methotrexate and citrovorum factor rescue. The antecedent pregnancy was molar in all patients. The known histologic diagnosis in 34 patients was hydatdiform mole and choriocarcinoma in 3. Up to March 1977, the duration of remissions ranged from 1 to 21 months. Complete and sustained remission was achieved in 91% of patients with nonmetastatic disease and in 2 of the 3 patients with metastases, without evidence of marrow or hepatic and with substantially reduced epithelial toxicity. Response to treatment and the number of courses required to achieve remission were determined solely on the basis of the human chorionic gonadotropin response as measured by the beta subunit radioimmunoassay.

Topics: Adolescent; Adult; Bone Marrow; Chemical and Drug Induced Liver Injury; Chorionic Gonadotropin; Drug Therapy, Combination; Epithelium; Female; Humans; Leucovorin; Liver; Methotrexate; Middle Aged; Neoplasm Metastasis; Pregnancy; Pregnancy Complications; Remission, Spontaneous; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Choriocarcinoma; Dactinomycin; Female; Humans; Leucovorin; Methotrexate; Pregnancy; 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

Topics: Adult; Choriocarcinoma; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Metastasis; Pregnancy; Uterine Neoplasms

Topics: Choriocarcinoma; Female; Humans; Injections, Intravenous; Leucovorin; Methotrexate; Pregnancy; Uterine Neoplasms

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

Treatment of the BeWo line of choriocarcinoma cells with methotrexate in doses that inhibit DNA synthesis causes a tenfold increase in synthesis of human chorionic gonadotropin and a threefold increase in activity of placental alkaline phosphatase. No concomitant increase in lactic dehydrogenase activity occurs under these conditions. This effect of methotrexate can be blocked by simultaneous addition of thymidine or folinic acid, neither of which alone increases human chorionic gonadotropin synthesis or placental alkaline phosphatase activity in BeWo cells.

Topics: Alkaline Phosphatase; Cells, Cultured; Choriocarcinoma; Chorionic Gonadotropin; DNA, Neoplasm; Dose-Response Relationship, Drug; Enzyme Induction; Female; Humans; L-Lactate Dehydrogenase; Leucovorin; Methotrexate; Neoplasm Proteins; Placenta; Pregnancy; RNA, Neoplasm; Thymidine; Uterine Neoplasms

Gestational trophoblastic malignancy, although rare, offers the clinician the opportunity of being able to cure a malignant disease with cytotoxic chemotherapy. Such an opportunity is fulfilled only when the progress of the post-molar patients is monitored and chemotherapy instituted as soon as the malignant transformation of the mole is documented. The management and treatment of nine cases is presented and discussed.

Topics: Adult; Choriocarcinoma; Female; Humans; Hysterectomy; Leucovorin; Mercaptopurine; Methotrexate; Pregnancy; Uterine Neoplasms

Experience with chemotherapy in advanced gynecologic malignancies is limited. In 6 patients, 2 of 4 with carcinoma of the cervix, and 1 patient with carcinoma of the ovary achieved partial remission when treated with a regimen of high dose methotrexate (240 mg/m2) followed by leucovorin rescue. On patient with metastatic trophoblastic disease achieved complete response (greater than 24 months). The number of doses of leucovorin 'rescue' was based on creatinine clearance. The advantage of rapid response and moderate toxicity indicate the need for further study of this regimen in the treatment of gynecologic malignancies.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Leucovorin; Methotrexate; Middle Aged; Ovarian Neoplasms; Pregnancy; Trophoblastic Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: Blood Cell Count; Blood Platelets; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Thrombocytopenia; Thrombocytosis; Time Factors; Trophoblastic Neoplasms; Uterine Neoplasms

Topics: Adult; Angiography; Antineoplastic Agents; Chorionic Gonadotropin; Female; Humans; Infusions, Parenteral; Leucovorin; Mercaptopurine; Methotrexate; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms

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