Chemotherapy For Gestational Trophoblastic Tumor Research Articles

Effects of Single-Agent and Combination Chemotherapy for Gestational Trophoblastic Tumors on Risks of Second Malignancy and Early Menopause

To assess the risks of second malignancy and early menopause in a large cohort of patients with gestational trophoblastic tumor who were treated with chemotherapy. A survey of patients treated at Charing Cross Hospital between 1958 and 2000 was performed in 2006 to assemble incidence data for subsequent malignancies and the age at menopause. Treatment records were reviewed for the regimens and durations, and the incidence of subsequent malignancies was compared with that in the national age-matched population. Data were obtained for 1,903 patients, with a mean follow-up of 16.9 years. Eighty-six patients developed a subsequent malignancy compared with an expected number of 79 (standardized incidence ratio [SIR], 1.1; 95% CI, 0.9 to 1.3). The overall risk was low for patients treated with single-agent methotrexate and folinic acid (MTX-FA; SIR, 0.7; 95% CI, 0.5 to 1.1) and also for patients treated with etoposide, methotrexate, and dactinomycin followed by cyclophosphamide and vincristine on alternating weeks (EMA-CO) with an SIR of 0.9 (95% CI, 0.4 to 2.2), but there were significantly increased risks of oral cancer, melanoma, meningioma, and leukemia. The cumulative risk of early menopause was low after MTX-FA but was substantial after EMA-CO, reaching 13% by age 40 years and 36% by age 45 years. Subsequent cancer risks for patients cured of gestational trophoblastic tumors with modern chemotherapy appear similar to those of the normal population with no overall increased risk of malignancy after MTX-FA or EMA-CO. However, there was evidence of an increased risk of leukemia after EMA-CO and some evidence of other site-specific increased risks based on small patient numbers. All major treatments except MTX-FA increased the risk of early menopause.

Characterisation of transient benign hCG elevations in women following chemotherapy for GTT

The occurrence of post-chemotherapy transient low level hCG elevations has been observed in a number of women treated for gestational trophoblastic tumours (GTT). The authors reviewed the records of patients treated at Charing Cross Hospital over the last 10 years and identified those with a benign rise in hCG. Stored serum samples were assayed for hCG, LH, FSH and oestradiol at varying points during patient management. The endocrine profile in patients experiencing benign hCG elevation is comparable with that seen in post-menopausal women, with low oestradiol, combined with greatly elevated LH and FSH levels. In contrast, women with genuine disease relapse as the cause of their post-chemotherapy hCG elevation had normal or only minor elevations of LH and FSH. These findings support the observation that a major rise in LH and FSH can be used as an indicator for benign pituitary hCG production in patients experiencing a low level rise in hCG levels following chemotherapy for GTT.

Risk of Abnormal Pregnancy Completing Chemotherapy for Gestational Trophoblastic Tumor

Matsui, Hideo; Iitsuka, Yoshinori; Susuka, Kiyomi; Yamazawa, Koji; Tanaka, Naotake; Seki, Katsuyoshi; Sekiya, Souei

Postmolar surveillance at a trophoblastic disease center that serves indigent women

Objective: The purpose of this study was to determine compliance with postmolar pregnancy surveillance in our indigent population. Study Design: Data for all women who were diagnosed with molar pregnancy from January 1996 through December 2000 were entered prospectively into a database. After remission, postmolar pregnancy surveillance was continued for 6 months. Patients whose condition required chemotherapy for gestational trophoblastic tumor had 12 months of follow-up. Medical records were reviewed. Results: Molar pregnancies occurred in 121 women: 103 Hispanic women (85%), 12 African American women (10%), and 6 white women (5%). Eighty-two women (68%) achieved remission without chemotherapy; 23 women (19%) were lost to follow-up without achieving remission, and 16 women (13%) had gestational trophoblastic tumor. Fifty-six Hispanic women (54%) completed postmolar pregnancy surveillance, compared with two African American women (11%, P <.01). Hispanic patients who were fluent in Spanish only were more likely to complete follow-up than bilingual Hispanic patients (62% vs 41%, P <.01). Conclusion: Hispanic women who were fluent in Spanish only were most likely to complete the recommended postmolar human chorionic gonadotropin surveillance. (Am J Obstet Gynecol 2003;188:1151-3.)

Risk of abnormal pregnancy completing chemotherapy for gestational trophoblastic tumor

Objective This study analyzed the outcome of the first pregnancy following chemotherapy for gestational trophoblastic tumor (GTT). Methods A total of 387 patients with GTT (85 patients with high-risk GTT and 302 patients with low-risk GTT) underwent chemotherapy at Chiba University Hospital between 1974 and 2000. Of these patients, 130 women (18 with high-risk GTT and 112 with low-risk GTT), who achieved remission and had at least one conception following chemotherapy, were included in the study. Results The outcomes of all the first subsequent pregnancies in women treated with methotrexate, actinomycin-D, or etoposide (including those switched to other regimens), or combination therapy, were comparable to those in the Japanese general population. However, the incidence of abnormal pregnancies (spontaneous abortion, still birth, repeat mole) was significantly higher in women who conceived within 6 months of completing chemotherapy (4/15; 40%) than in those who conceived after the recommended waiting period of more than 12 months (10/95; 10.5%) ( P = 0.028). Conclusion Patients with GTT who achieved remission after chemotherapy with methotrexate, actinomycin-D, or etoposide, or combination therapy, may anticipate a normal future reproductive outcome. As pregnancies occurring within 6 months following remission are at risk of abnormalities, a waiting period of at least 6 months after chemotherapy for GTT is suggested.

The effect of early pregnancy following chemotherapy on disease relapse and foetal outcome in women treated for gestational trophoblastic tumours.

Little literature exists on the safety of early pregnancy following chemotherapy. Here we assess the rate of relapse and foetal outcome in women who have completed single and multi-agent chemotherapy for gestational trophoblastic tumours. The records of 1532 patients treated for persistent gestational trophoblastic tumours at Charing Cross Hospital between 1969 and 1998 were reviewed. Patients were defined as receiving single agent or multi-agent treatment. Relapse rates and foetal outcome were reviewed in the 230 patients who became pregnant within 12 months of completing chemotherapy. In the single agent group 153 (22%) of 691 patients conceived early. Three subsequently relapsed. In the multi-agent group, 77 (10%) of 779 patients conceived early, two then relapsed. Relapse rates were 2% (3 out of 153) and 2.5% (2 out of 77) for each group compared to 5% and 5.6% in the comparative non-pregnant groups. Outcomes of 230 early pregnancies: 164 (71%) delivered at full term, 35 (15%) terminations, 26 (11%) spontaneous abortions, three (1.3%) new hydatidiform moles and two (1%) stillbirths. Early pregnancies were more common in the single agent group (P<0.001), but spontaneous miscarriages and terminations were more likely to occur in the multi-agent group (P=0.04 and 0.03, respectively). Of the full-term pregnancies, three (1.8%) babies were born with congenital abnormalities. Patients in either group who conceive within 12 months of completing chemotherapy are not at increased risk of relapse. Though, we still advise avoiding pregnancy within 12 months of completing chemotherapy, those that do conceive can be reassured of a likely favourable outcome.British Journal of Cancer (2002) 86, 26–30. DOI: 10.1038/sj/bjc/6600041 www.bjcancer.com© 2002 The Cancer Research Campaign

Pregnancy Outcomes of Patients Who Conceived within 1 Year after Chemotherapy for Gestational Trophoblastic Tumor: A Clinical Report of 22 Patients

Objective. The aim of this study was to explore the risk of pregnancy of patients who conceived within 1 year after successful chemotherapy for gestational trophoblastic tumor (GTT).Methods. From 1966 to 1996, 22 patients who conceived within 1 year after chemotherapy were followed up and analyzed retrospectively.Results. Among 22 patients, 9 had term deliveries and 1 had a premature birth, 6 had induced abortion at the patient's request, and 6 had therapeutic abortion because of various indications such as repeated hydatidiform mole (1 case), intrauterine death (1 case), inevitable abortion (1 case), and threatened abortion (3 cases). The fetal loss rate was 27.1% (6/22). The incidence rate of gestational trophoblastic disease (GTD) was 9.1% (2/22). The incidence rate of GTT was 4.5% (1/22). The average interval between completion of chemotherapy and pregnancy was 10.25 months in the group of term pregnancies and 5.86 months in that of fetal loss (P < 0.05), indicating that the longer the interval, the lesser the risk of GTD.Conclusion. The results suggest that contraception for 1 year is necessary in patients with GTT after successful chemotherapy. However, in the case of a patient who conceives within 1 year, it is not necessary to terminate pregnancy, but the pregnancy must be carefully watched.

Outcome of Pregnancies Occurring Before Completion of Human Chorionic Gonadotropin Follow-Up in Patients With Persistent Gestational Trophoblastic Tumor

Objective. To determine the outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients treated with chemotherapy for gestational trophoblastic tumor. Methods. Retrospective record review of patients with gestational trophoblastic tumor who conceived before standard hCG follow-up was completed during 1973‐1998. Results. Forty-three patients treated for gestational trophoblastic tumors conceived before human chorionic gonadotropin follow-up was completed. The antecedent pregnancy was complete mole in 31 (72.1%) and partial mole in 12 (27.9%) patients. Of the 43 patients, 39 (90.7%) had stage I, 1 had stage II, and 3 had stage III disease. The mean interval from human chorionic gonadotropin remission to new pregnancy was 6.3 months (range 1‐11 months). Ten patients underwent elective termination and four patients were lost to follow-up. Of the remaining 29 patients, 22 (75.9%) had term live births, 3 (10.3%) had preterm delivery, 3 had spontaneous abortion, and 1 (3.5%) had a repeat mole. Two cases of fetal anomalies were detected; one was inherited polydactyly and the other was hydronephrosis. One patient developed choriocarcinoma with lung involvement and underwent cesarean section at 28 weeks; a normal fetus was delivered and no choriocarcinoma was detected in the placenta. Conclusion. Pregnancies occurring in patients treated for gestational trophoblastic tumor before standard human chorionic gonadotropin follow-up is completed may continue under close clinical surveillance since the majority have a favorable outcome. However, patients should also be advised of the low but important risk of delayed diagnosis in case tumor relapse develops during early subsequent pregnancy. © 1999 Academic Press

Chemotherapy for gestational trophoblastic tumours hastens menopause by 3 years

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 χ 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 χ 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 χ 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.

Combination but not single-agent methotrexate chemotherapy for gestational trophoblastic tumors increases the incidence of second tumors.

No increase in second tumor incidence was found in a previous analysis of women treated with chemotherapy for gestational trophoblastic tumors (GTT). More patient years at risk enabled a further analysis of the risk of second tumors to be performed in the 1,377 women treated in this until up to 1990. Health questionnaires were returned on 93.3% of patients who successfully completed chemotherapy and were living in the United Kingdom. The remainder were flagged for death or developing further cancers by the Office of Population Census and Surveys and by the Thames Cancer Registry. Incidence density analysis was performed based on 15,279 person-years of observation available. Standardized incidence ratio (SIR) was used to estimate the relative risk (RR) of second tumors associated with the treatment. To calculate the expected number, the actual incidence rates observed by the Thames Cancer Registry during the same calendar period of observation were used. An overall 50% excess of risk (RR = 1.5; 95% confidence interval [CI], 1.1 to 2.1; P < .011) was observed: there were 37 second tumors, when 24.5 were expected. For specific second tumors, the risk was significantly increased for myeloid leukemia (RR = 16.6; 95% CI, 5.4 to 38.9), colon (RR = 4.6; 95% CI, 1.5 to 10.7), and breast cancer when the survival exceeded 25 years (RR = 5.8; 95% CI, 1.2 to 16.9). The risk was not significantly increased among the 554 women receiving single-agent therapy (RR = 1.3; 95% CI, 0.6 to 2.1). Leukemias only developed in patients receiving etoposide plus other cytotoxic drugs. This study suggests that there is a slight increased risk of second tumors after sequential or combination chemotherapy for GTT. This has become apparent since the introduction of etoposide and longer follow-up.

Chemotherapy for Gestational Trophoblastic Tumors

Virtually 100% of patients with nonmetastatic and low-risk metastatic trophoblastic tumors are now curable by only conventional chemotherapeutic agents such as methotrexate, actinomycin D, or their combination with or without other agents. However, approximately 30% of high-risk patients with metastatic trophoblastic tumors are resistant to conventional chemotherapy. All of the high-risk patients resistant to chemotherapy are those with metastatic choriocarcinoma. Thus, the efficacy of multidrug chemotherapy and combination chemotherapy of cisplatin or VP16-213 with other agents is now being examined.

Fertility after chemotherapy for male and female germ cell tumours

Gonadal function was assessed in fifty-nine men and thirty-one women who had successfully completed chemotherapy with the POMB/ACE regimen for germ cell tumours. Seventeen (81%) of the twenty-one men who had not received paraaortic radiotherapy, whose original tumour bulk was less than 5 cm and whose duration of chemotherapy was less than 6 months, recovered spermatogenesis compared with twelve (32%) of thirty-eight patients who had either larger tumour masses or longer courses of chemotherapy, or both. All but one of the seventeen women in whom menstruation could have been expected to recur are now menstruating. This study suggests that the great majority of patients treated with POMB/ACE chemotherapy for germ cell tumours will recover fertility.

Chemotherapy for gestational trophoblastic tumors.

Virtually 100% of patients with nonmetastatic and low-risk metastatic trophoblastic tumors are now curable by only conventional chemotherapeutic agents such as methotrexate, actinomycin D, or their combination with or without other agents. However, approximately 30% of high-risk patients with metastatic trophoblastic tumors are resistant to conventional chemotherapy. All of the high-risk patients resistant to chemotherapy are those with metastatic choriocarcinoma. Thus, the efficacy of multidrug chemotherapy and combination chemotherapy of cisplatin or VP16-213 with other agents is now being examined.

Long-term effects of chemotherapy on lymphocyte chromosomes from patients treated for gestational trophoblastic tumours.

A cytogenetic follow-up study of patients treated with chemotherapy for gestational trophoblastic tumours was undertaken. In some cases, high levels of chromosome damage were found to persist in lymphocytes for several years after completion of therapy. These results are compared with those found in similar studies of non-malignant and other malignant diseases. The relevance of these findings to the risk of subsequent chemotherapy-induced malignancy is discussed.

Pregnancy after Cytotoxic Chemotherapy for Gestational Trophoblastic Tumours

Cytotoxic chemotherapy is a potential cause of sterility in young women and of malformations in the offspring of patients who conceive after treatment. The present authors, with the aim of identifying drug regimens that are compatible with fertility and not teratogenic, studied the obstetrical histories of women who entered remission after receiving cytotoxic chemotherapy for gestational trophoblastic tumors. Up-to-date obstetrical records on 445 women were available. Of the 217 who wished to conceive, 187 (86 per cent) succeeded in having at least one live birth each. Twenty-three (11 per cent) conceived but did not achieve a live birth, and seven (3 per cent) failed to conceive. The mean duration of chemotherapy was 4 months. The average age on completion of treatment was 24.9 years for those who had live births, 24.4 years for those who conceived but had no live birth, and 24.4 years for those who did not conceive at all. The average age of the women who did not want a pregnancy was 31.5 years. For each of the four groups of women, Table 1 shows the mean and maximum amounts of cytotoxic drug received. Methotrexate was given to all but two patients, neither of whom had tried to conceive. Analysis of each drug individually showed no significant difference between the mean amounts given to the women who achieved live births and those who did not. Live births occurred after all of the agents used, apart from cisplatin and etoposide. There was little difference, in the maximum doses given, between the group who had live births and the groups who had none. Combination chemotherapy was given to 43 per cent of the women who had live births, to 57 per cent of those who conceived but had no live births, and to 71 per cent of those who failed to conceive. These differences were not significant, but there was a distinct difference when the number of drugs received was considered. Women who were given three or more drugs in combination were less likely to have live births or to conceive at all than those given methotrexate alone or in combination with only one other drug (P < 0.001). Those who received actinomycin D or vincristine were less likely to have live births than the women who did not receive either drug (P < 0.01 and P < 0.05, respectively). None of the other drugs used in combination showed this significance, and none, including actinomycin and vincristine, showed any dose-response relation.

Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours.

To examine the possibility that cytotoxic drugs may cause sterility or congenital malformations in the offspring of women of childbearing age who are cured of cancer a study was conducted of the obstetric histories of 445 long term survivors treated in this unit with chemotherapy for gestational trophoblastic tumours between 1958 and 1978. After completing treatment 97% of those who wished for a pregnancy (49% of all women studied) conceived and 86% had at least one live birth. All these women had received methotrexate. Of the 47 women who wished to conceive and whose combination therapy included cyclophosphamide, 37 (79%) had a live birth. Women who received three or more drugs were less likely to have a live birth than those who received methotrexate alone or with only one other drug (p less than 0.001). There was no statistically significant excess of congenital malformations. These results are strong evidence that the cytotoxic drug regimens used in this unit for treating gestational trophoblastic tumours are compatible with the preservation of fertility in most women and not associated with any increase in congenital abnormalities.

No Increase in Second Tumors after Cytotoxic Chemotherapy for Gestational Trophoblastic Tumors

No Increase in Second Tumors after Cytotoxic Chemotherapy for Gestational Trophoblastic Tumors

Central nervous system metastases of choriocarcinoma. 23 years' experience at Charing Cross Hospital.

Between 1957 and February 1981, 782 patients received cytotoxic chemotherapy for gestational trophoblastic tumors (GTT) in the Department of Medical Oncology, Charing Cross Hospital (London, England). Sixty-nine (8.8%) patients had central nervous system (CNS) metastases. Thirty-three of them (48%) presented with CNS disease prior to treatment (CNS presentation group), and 36 (52%) developed CNS disease while on treatment, or relapsed in the CNS after an initial complete or partial remission (late CNS group). Treatment included systemic and intrathecal chemotherapy, and, in several cases neurosurgery, whole brain irradiation, and immunotherapy. Life-table analysis projects an overall survival of 49% for the CNS presentation group and 6% for the late CNS group. Prognosis has improved with time; prior to 1974, 38% of the CNS presentation group and none of the late CNS group survived. After 1974 overall survival has been 80% in the CNS presentation group and 25% in the late CNS group. The principal elements in the successful management of such cases are: (1) CNS prophylaxis with intrathecal methotrexate for patients at risk of developing brain metastases; (2) early detection of CNS lesions by prompt recognition of their clinical features, measurement of the ratio of CSF to serum human chorionic gonadotropin concentration, and appropriate use of computerized tomography of the brain; and (3) a combination of systemic and intrathecal therapy for patients developing brain secondaries.