Elsevier

Gynecologic Oncology

Volume 125, Issue 3, June 2012, Pages 576-579
Gynecologic Oncology

Relapse rates after two versus three consolidation courses of methotrexate in the treatment of low-risk gestational trophoblastic neoplasia

https://doi.org/10.1016/j.ygyno.2012.03.003Get rights and content

Abstract

Objective

Methotrexate (MTX) alternating with folinic acid is a commonly used treatment regimen for low-risk gestational trophoblastic neoplasia (GTN). In The Netherlands, two courses of MTX are administered after normalization of serum human chorionic gonadotrophin (hCG) levels (consolidation courses), whereas in the United Kingdom, three consolidation courses are given. In a retrospective setting we compared relapse rates of women completing MTX therapy for low-risk GTN in The Netherlands and the UK.

Methods

From 1980 to 2008, 351 patients were collected from the Dutch Central Registry for Hydatidiform Moles and records from the Dutch Working Party on Trophoblastic Disease. From the Charing Cross Hospital Trophoblast Disease Centre (London), 600 low-risk GTN patients were identified from 1992 to 2008.

Results

In 4.0% of patients relapse occurred after MTX treatment with three consolidation courses, whereas 8.3% of patients relapsed after MTX treatment with two consolidation courses (p = 0.006). Although patients from The Netherlands had a higher level of hCG (p < 0.001) and more patients had metastases before the start of treatment (p = 0.012), the number of courses of MTX to achieve a normal hCG did not differ significantly between patients from The Netherlands and the UK (p = 0.375).

Conclusions

Relapse rates were higher in patients treated with two consolidation courses of MTX. Although other factors might have influenced the observed difference in relapse rates, three courses of consolidation chemotherapy may be preferable to two in the treatment of low-risk GTN in order to decrease the risk of disease relapse. A prospective randomized study would be required to confirm these findings.

Highlights

► In a retrospective setting we compared relapse rates after MTX for low-risk GTN in the Netherlands and the UK. ► Relapse rates were higher in patients treated with two consolidation courses of MTX.

Introduction

A hydatidiform mole (HM) is an abnormal pregnancy with excessive proliferation of placental villi but severely stunted or absent embryonic development. This condition affects one to three per 1000 pregnancies in western countries [1], [2] and can be classified into complete (CHM) or partial HM (PHM) [3]. Management of both CHM and PHM is similar: surgical evacuation followed by regular measurement of serum human chorionic gonadotrophin (hCG) until the levels have returned to normal. Normalization occurs in 80–90% of women. However, in the presence of three consecutive static or rising weekly hCG levels during follow-up, patients are defined as having gestational trophoblastic neoplasia (GTN). In The Netherlands, an additional criterion was added to this definition in 1993. At least one of the values should exceed the 95th percentile of the hCG regression corridor of uneventful decline as constructed by Yedema et al. [4].

GTN is an indication for chemotherapeutic treatment. Depending on the stage of the disease, patients are treated with either single-agent therapy for low-risk disease, or multi-agent therapy for high-risk disease [5]. In The Netherlands and the UK, low risk patients receive intramuscular methotrexate (MTX) (1 mg/kg or 50 mg total, respectively) on days 1, 3, 5 and 7 alternating with oral folinic acid (FA) 15 mg on days 2, 4, 6, and 8, repeated every 2 weeks [6], [7], [8]. Treatment continues until the hCG level is normal and then for a further consolidation period. The number of courses of MTX administered after normalization of serum hCG levels in order to eradicate the remaining tumor cells differs between The Netherlands and the UK. In The Netherlands, two consolidation courses are given, whereas in the UK, MTX treatment is consolidated over three further courses after normalization of hCG levels [4], [8], [9]. Evidence exists that relapse rates after MTX treatment diverge between The Netherlands and the UK, although definitions of relapse differed between these studies [10], [11]. Disease relapse requires treatment with multi-agent chemotherapy, which, in contrast to MTX, is associated with an increased incidence of secondary malignancies and increases the risk of an early menopause [12], [13], [14]. Therefore an additional course of MTX would be preferred if this decreases the chance of developing relapsed disease. In the present study we have retrospectively compared the percentage of disease relapse in a large cohort of women with low-risk GTN, treated with either two (The Netherlands) or three (UK) consolidation courses of MTX.

Section snippets

Methods

In The Netherlands, patients with gestational trophoblastic disease (GTD) are registered at the Dutch Central Registry for Hydatidiform Moles (DCRHM) residing at the Radboud University Nijmegen Medical Centre (RUNMC). This voluntary registry serves as an epidemiological database and provides a national hCG assay service to gynecologists. Between 1977 and 2010, 3983 patients were registered at the DCRHM. Patients are treated in different referral hospitals with the Dutch Working Party on

Results

From 1980 to 2008, 351 women with low-risk GTN with normalization of hCG levels after MTX treatment were collected from records from the DCRHM and the Dutch Working Party on Trophoblastic Disease. From the Charing Cross Hospital database, 600 low-risk patients successfully treated with MTX were identified from 1992 to 2008. Patient characteristics of these patients before the start of MTX treatment are shown in Table 1. Mean maternal age at diagnosis was 30.3 and 31.1 years in patients from both

Discussion

The present study showed that 4.0% of low-risk GTN patients relapsed after MTX treatment with three consolidation courses after normalization of hCG levels, whereas 8.3% of patients relapsed after MTX treatment with two consolidation courses after hCG normalization. Several previous studies have examined relapse rates after MTX treatment for low-risk GTN, although some have combined patients normalizing on MTX with patients who had progressive disease on MTX and therefore had to switch to more

Conflict of interest statement

None declared.

Acknowledgments

MJS is supported by the National Commissioning Group and the Dept of Health/Cancer Research UK funded Imperial College Experimental Cancer Medicine Centre.

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This study has been presented at the 17th Meeting of the European Society of Gynecological Oncology (ESGO, Milan) and at the 16th congress of the International Society for the Study of Trophoblastic Diseases (ISSTD, Budapest).

1

Board members of the Dutch Working Party on Trophoblastic Disease.

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