levoleucovorin and Choriocarcinoma

Choriocarcinoma is an aggressive malignancy of trophoblastic tissue, typically of gestational etiology. Sporadic, nongestational cases are rarely found outside of the gonads. There are only 31 cases of primary choriocarcinoma of the colon reported in the literature. As a consequence of their rarity and aggressive nature, timely diagnosis and effective treatment have proved challenging, and prognosis is very poor. For that reason, we present a rare case with prolonged survival in the youngest reported patient .. A 26-year-old Caucasian woman presented with abdominal cramping and rectal and vaginal bleeding. Elevated serum human chorionic gonadotropin and an 8-cm right-sided mass seen on ultrasound suggested ectopic pregnancy. The patient was treated with methotrexate; however, her symptoms persisted, and her human chorionic gonadotropin levels continued to rise. Further workup showed a large mass of the sigmoid colon with multiple hepatic lesions suggestive of metastases. Preliminary pathology showed adenocarcinoma. Despite surgical resection and initiation of FOLFOX chemotherapy (folinic acid, fluorouracil, oxaliplatin), the patient had significant clinical deterioration, and her human chorionic gonadotropin increased exponentially. Further pathological review showed two distinct phenotypes: adenocarcinoma merging with choriocarcinoma. The result of evaluation of the metastatic lesions was also positive for choriocarcinoma. Treatment was promptly changed to a choriocarcinoma-targeting chemotherapy regimen of EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), resulting in rapid and dramatic response. The patient had mild progression after 1 year and was switched back to FOLFOX with bevacizumab. After five cycles, scans showed further progression, and the patient was started on third-line therapy with FOLFIRI (folinic acid, fluorouracil, irinotecan) and bevacizumab. Eighteen months after her diagnosis, the patient was alive and maintaining an overall response.. Our patient achieved a marked response and prolonged survival. Although a comprehensive review of the literature showed that survival with these tumors has improved over the past 10 years, prognosis remains poor. Currently, there is no established algorithm for the management of these rare tumors, but both the literature and our patient's case indicate that a choriocarcinoma-targeted regimen is critical for survival. Further evaluation of these rare tumors is warranted in order to identify pathological patterns that may help in the diagnosis, management, and survival of these malignancies.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Colon; Female; Fluorouracil; Humans; Leucovorin; Pregnancy

Gestational choriocarcinoma associated with ectopic pregnancy is an extremely rare event. We report a case of a choriocarcinoma arising from a cornual pregnancy.. The patient is a 35-year-old G8 P2052 who was referred to our department due to failure of treatment for a suspected ectopic pregnancy. The patient had initially been treated with methotrexate injection but her beta-hCG levels reached a plateau 3 weeks later and, despite another two methotrexate injections, started to rise. The patient underwent dilation and curettage that did not reveal any trophoblastic tissue. A diagnostic hysteroscopy that followed demonstrated occluded ostia of the left tube. The patient subsequently underwent diagnostic laparoscopy that revealed a mass in the left cornua, which was removed with wedge-wide resection. Histologic evaluation revealed choriocaricnoma.. Appropriate monitoring of beta-hCG titers following conservative management of suspected ectopic pregnancy is important, not only to diagnose persistent ectopic gestation, but also to rule out the presence of malignant trophoblastic disease, albeit the latter is a rare diagnosis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Fallopian Tube Neoplasms; Female; Humans; Leucovorin; Methotrexate; Pregnancy; Pregnancy, Ectopic

Twenty-five patients with CNS metastases of choriocarcinoma were treated with a regimen incorporating etoposide, methotrexate, and actinomycin (EMA) alternating weekly with vincristine and cyclophosphamide (CO). The dose of methotrexate was increased to 1 g/m2. Eighteen patients presented with CNS metastases, or developed them on inappropriate treatment started elsewhere. Following EMA/CO chemotherapy, three patients died within the first 3 weeks, one is alive with active disease, one died with drug resistance, and 13 (72%) patients are surviving disease-free. Two of seven patients (29%) who developed CNS metastases on treatment with EMA/CO or relapsed after EMA/CO are disease-free after additional chemotherapy and surgery. The contribution toward survival of the craniotomy in six of 18 patients treated initially or early with EMA/CO remains unclear, but was crucial to those patients with drug resistance.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Choriocarcinoma; Chorionic Gonadotropin; Clinical Trials as Topic; Craniotomy; Dactinomycin; Doxorubicin; Etoposide; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Prognosis; Vincristine

45 patients (43 ovarian carcinoma and 2 chorionepithelioma) were treated with high doses of methotrexate and intramuscularly application of leucovorin according to Mathé et al. In comparison a group of 19 patients (ovarian carcinoma only) was treated with methotrexate and leucovorin-tablets. The toxic effects on leucocytes and platelets were equal in both groups. Due to slightly different doses of leucovorin in both groups an enteral resorption rate of more than 90 p.c. is calculated. Because of the simple way of application the suggested high-dose therapy with methotrexate and leucovorin-tablets seems to be most convenient in the moment.

Topics: Administration, Oral; Blood Platelets; Choriocarcinoma; Drug Therapy, Combination; Female; Humans; Injections, Intramuscular; Leucovorin; Leukocytes; Methotrexate; Middle Aged; Ovarian Neoplasms; Pregnancy

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

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

We report a rare case of primary choriocarcinoma of the colon. A 58-year-old woman underwent Hartmann's procedure to remove a sigmoid colon tumor, and pathological examination confirmed choriocarcinoma that had originated from the colon. Radical surgery combined with chemotherapy gives the best chance of long-term survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Colon, Sigmoid; Colonoscopy; Dactinomycin; Etoposide; Female; Humans; Leucovorin; Methotrexate; Middle Aged; Neoplasm Grading; Neoplasm Staging; Sigmoid Neoplasms

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

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

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

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

Chemotherapy may induce acute ovarian failure, but in women who retain gonadal function throughout chemotherapy, the late effects upon ovarian function are unknown. A retrospective controlled survey was performed to ascertain whether chemotherapy for gestational trophoblastic tumours (GTT) results in premature menopause. Questionnaires were sent to 1,489 women diagnosed between 1971 and 1990 with GTT, including 1089 who had received chemotherapy and 400 who had not received chemotherapy (controls). Responses were obtained from 972 chemotherapy-treated patients and 327 controls. 124 women were not evaluable for menopause date as they had undergone hysterectomy as part of the treatment for GTT or had developed permanent amenorrhoea during chemotherapy. Overall, 172 women reported that they were postmenopausal, including 157 women who had received chemotherapy. The median age at menopause for the evaluable population was 50 years (range 25-56 years). The age at menopause was significantly earlier in the treated arm (median 50, range 25-56 years) than in the controls (median 53, range 40-57 years) (logrank test chi 2 = 12.6, P = 0.0004). Menopause occurred significantly earlier in women treated with combination chemotherapy (median 49, range 25-56 years) compared with single agent methotrexate (median 51, range 25-56 years) (logrank test chi 2 = 8.3, P = 0.004). However, the age at completion of chemotherapy in the treated arm did not influence the age of menopause (proportional Hazards chi 2 = 1.99, P = 0.16). Chemotherapy for GTT induces menopause 3 years earlier than it occurs in women with GTT who do not receive chemotherapy. Although the difference is statistically significant, the magnitude is modest and most women can be reassured that neither fertility nor postmenopausal osteoporosis will be greatly affected.

Topics: Adult; Antineoplastic Agents; Choriocarcinoma; Dactinomycin; Etoposide; Female; Follow-Up Studies; Humans; Hydroxyurea; Leucovorin; Menopause, Premature; Mercaptopurine; Methotrexate; Middle Aged; Pregnancy; Retrospective Studies; Risk Factors; Trophoblastic 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

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

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Choriocarcinoma; Cyclophosphamide; Doxorubicin; Female; Humans; Leucovorin; Lung Neoplasms; Methotrexate; Neoplasm Regression, Spontaneous; Vaginal Neoplasms

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

Primary cervical choriocarcinoma is a rare disease; since 1915 only about 60 cases have been published. The case presented here can be defined as primary cervical choriocarcinoma since it fulfills all the criteria delineated previously.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cervix Uteri; Choriocarcinoma; Female; Humans; Immunoenzyme Techniques; Leucovorin; Methotrexate; Uterine Cervical 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

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

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

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

Methotrexate (MTX) shows consistent cytotoxicity for melanoma cells in vitro but it is ineffective in clinical use at equivalent concentrations in vivo. This apparent paradox has been investigated by cell culture techniques and results quantified by cell number. In an in vitro model of high dose MTX therapy followed by leucovorin rescue (HD-MTX-LCR) there was survival of both melanoma and choriocarcinoma cell lines but not of an acute lymphocytic leukaemia cell line. The 70H metabolite of MTX was identified by HPLC in plasma samples of melanoma patients treated by HD-MTX-LCR, in which MTX concentrations approximately 10(-5) M were maintained for 24 h. However, metabolism per se is unlikely to account for the lack of response to MTX clinically. In vitro 70H MTX (10(-7) - 10(-6) M) was two orders of magnitude less cytotoxic for melanoma than MTX (10(-9) - 10(-8) M). The cellular accumulation of [3H]-MTX, using a rapid gradient centrifuge technique for separation of melanoma cells from medium, was reduced in the presence of 70H-MTX. The results suggest that reduced cellular uptake of MTX combined with biochemical rescue of tumour cells may partially explain the paradoxical lack of clinical response of melanoma to the drug.

Topics: Animals; Cell Count; Cell Line; Cell Survival; Choriocarcinoma; Humans; Leucovorin; Leukemia, Lymphoid; Male; Melanoma; Methotrexate; Mice

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

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: 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

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

Choriocarcinoma with a primary site in the chest is rarely found. Characteristically, it is seen in young men presenting with cough, gynecomastia and chest pain. The disease is invariably fatal. The presently accepted therapy (triple therapy), consisting of methotrexate, actinomycin D and chlorambucil, has been unsuccessful to date.

Topics: Adult; Choriocarcinoma; Cyclophosphamide; Dactinomycin; Humans; Leucovorin; Male; Mediastinal Neoplasms; Methotrexate; Vincristine

Topics: Adult; Autopsy; Choriocarcinoma; Drug Resistance; Female; Hemoperitoneum; Hepatomegaly; Humans; Leucovorin; Liver Circulation; Liver Neoplasms; Methotrexate; Pregnancy; Radionuclide Imaging

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Cell Division; Choriocarcinoma; Chorionic Gonadotropin; Dactinomycin; Drug Resistance; Drug Therapy, Combination; Female; Folic Acid Antagonists; Humans; Kinetics; Leucovorin; Methotrexate; Mice; Mitosis; Neoplasm Metastasis; Neoplasms; Pregnancy; Trophoblastic Neoplasms; Vinblastine

Topics: Age Factors; Child; Choriocarcinoma; Female; Humans; Leucovorin; Methotrexate; Neoplasm Metastasis; Ovarian Neoplasms; Pregnancy; Prognosis

Topics: Breast Neoplasms; Choriocarcinoma; Female; Head; Head and Neck Neoplasms; Humans; Leucovorin; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Methotrexate; Neoplasm Metastasis; Neoplasms; Ovarian Neoplasms; Pregnancy; Remission, Spontaneous; Uterine Cervical Neoplasms

Topics: Adolescent; Adult; Aged; Carcinoma, Squamous Cell; Child, Preschool; Choriocarcinoma; Chorionic Gonadotropin; Female; Humans; Infusions, Parenteral; Injections, Intravenous; Leucovorin; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lung Neoplasms; Male; Methotrexate; Middle Aged; Pregnancy; Teratoma; Testicular Neoplasms

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

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