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ethotrexate for 2000 FIGO low-risk gestational trophoblasticeoplasia patients: efficacy and toxicity

ihad Elias Chalouhi, MD; François Golfier, MD, PhD; Pauline Soignon, MD; Jerome Massardier, MD;ean-Paul Guastalla, MD; Veronique Trillet-Lenoir, MD; Anne-Marie Schott, MD, PhD; Daniel Raudrant, MD

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BJECTIVE: We sought to review efficacy and toxicity of an 8-dayethotrexate (MTX) regimen in the treatment of patients with low-risk

estational trophoblastic neoplasia (GTN) from the French Trophoblas-ic Disease Reference Center.

TUDY DESIGN: Between 1999 and 2006, 142 low-risk GTNs wereiagnosed according to International Federation of Gynecology andbstetrics (FIGO) criteria for GTN and to the FIGO scoring system. We

eport their characteristics, remission/resistance/recurrence rates, andreatment toxicity.

ESULTS: The 8-day MTX regimen achieved a 77.5% remission rate.

m J Obstet Gynecol 2009;200:643.e1-643.e6.

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ree until the time of analysis. Severe (grade 3 or 4) blood/bone mar-ow toxicity and metabolic/laboratory toxicity was noted in 4.2% ofases, of which 2 (1.4%) were grade 4.

ONCLUSION: For patients with GTN diagnosed according to FIGO cri-eria and considered low risk according to the FIGO scoring system, an-day MTX regimen is an adequate treatment associating a high rate ofemission to a low rate of toxicity.

ey words: efficacy, low-risk gestational trophoblastic neoplasia,ethotrexate, toxicity, 2000 International Federation of Gynecology

ll patients but 1 (99.9%) achieved remission and remained disease and Obstetrics scoring

ite this article as: Chalouhi GE, Golfier F, Soignon P, et al. Methotrexate for 2000 FIGO low-risk gestational trophoblastic neoplasia patients: efficacy and toxicity.

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he worldwide incidence of tropho-blastic disease ranges between 0.5-

.3/1000 live births of which 5-20%volve toward trophoblastic tumor andequire chemotherapy.1,2 Gestationalrophoblastic neoplasia (GTN)3 re-ponds excellently to chemotherapy4 buteeds to be treated by, or at least in con-ultation with, physicians experienced inhe management of this disease spec-rum.5 The morbidity and mortality is 9imes higher when an inexperiencedhysician treats such patients.6 Once di-gnosed, this disease is staged according

rom the Université de Lyon, F-69622 (Drs Cenoir, Schott, and Raudrant); Hospices Civilaladies Trophoblastiques (Drs Chalouhi, G

chott, and Raudrant); Hospices Civils de Lyobstétrique (Drs Chalouhi, Golfier, Soignon,yon-Sud, Service de Chirurgie Gynécologiquaudrant); Centre Hospitalier Lyon-Sud, Servôpital Edouard Herriot, Département d’Info

’Appui Epidémiologique (Dr Schott); CentrDr Guastalla), Lyon, France.

eceived July 29, 2008; revised Jan. 16, 2009;

eprints: François Golfier, MD, PhD, Centre de Rervice de Gynécologie-Obstétrique, Hôtel-Dieurance. [email protected].

o the International Federation of Gyne-ology and Obstetrics (FIGO) 2000 clas-ification.7,8 In 1956, Li et al9 first suc-essfully treated choriocarcinoma, fatalp until then, with methotrexate (MTX).ince then, chemotherapy using MTXmerged as first-line, single-agent ther-py for low-risk (metastatic and non-etastatic) GTN.4,10-14 Many single-

gent MTX protocols were identifiedegarding the association with foliniccid, the dose, and the frequency withinach treatment course. However, there iss yet no consensus on a single best reg-

uhi, Golfier, Soignon, Massardier, Trillet-Lyon, Hôtel-Dieu, Centre de Référence des

er, Soignon, Massardier, Trillet-Lenoir,ôtel-Dieu, Service de Gynécologie

ssardier, and Raudrant); Centre Hospitaliert Cancérologie (Drs Golfier, Massardier, andd’Oncologie Médicale (Dr Trillet-Lenoir);ation Médicale en Cancérologie et Celluleon Bérard, Service d’Oncologie Médicale

epted March 6, 2009.

rences des Maladies Trophoblastiques,Lyon, 1 Place de l’Hôpital, 69002, Lyon,

b/j.ajog.2009.03.011

JUNE 2009 Americ

men as the choice often depends on lo-al experience.15 In a previous publica-ion, we found it difficult to comparereatment results for GTN across theorld because of the heterogeneity of pa-

ient groups and because of the wide va-ieties in chemotherapy regimen used.16

ne of the aims of the 2000 FIGO stag-ng/scoring system was to minimize thiseterogeneity to allow comparison ofreatment results between published re-orts. In our Trophoblastic Disease Ref-rence Center, we decided to use thiscoring system to define patients at lowisk and we chose the modified regimenf Bagshawe et al17 as first-line treat-ent. To date, there are scarce data of

esults of treatment for patients withTN classified according to the FIGO

coring system. We report our experi-nce with low-risk trophoblastic tumorsreated with single-agent MTX.

ATERIALS AND METHODShe medical records of all the patients

egistered at the French Trophoblasticisease Reference Center between No-

ember 1999 and December 2006 wereeviewed. After the diagnosis of tropho-

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6

ion, the patients were followed byeekly serum human chorionic gonado-

ropin (hCG) measurements until hCGevel returned to normal. When the-hCG becomes undetectable, further

pecimens are obtained either for 6onths in the case of partial mole or

omplete mole in which hCG level be-omes normal in � 8 weeks from suctionvacuation; or for a year in the case ofomplete mole for which hCG level didot normalize before 8 weeks. Contra-eption is recommended during this sur-eillance period, to avoid teratogenicisk from chemotherapy and to preventonfusion between a new pregnancy andisease recurrence.4

Although Van Trommel et al18 re-ently provided evidence of the potentialiagnostic ability of the hCG ratio in de-ecting GTN earlier than the criteria ofhe FIGO 2000, we used the latter to di-gnose GTN. The agreed FIGO 2000 cri-eria7 include: (1) plateau of hCG lastingor 4 measurements during a period of �

weeks (days 1, 7, 14, and 21); (2) anncrease of hCG of � 3 weekly consecu-ive measurements for � 2 weeks (days 1,, and 14); (3) hCG level remaining ele-ated for � 6 months; and (4) histologiciagnosis of choriocarcinoma.In the case of hCG remaining elevated

t 6 months, false-positive hCG shoulde considered together with quiescentestational trophoblastic disease and pi-uitary hCG.

Before the start of chemotherapy, a ra-iologic workup is done, consisting of ahoracoabdominal tomography (with andditional chest radiograph in case thehoracic scan showed metastases), a pel-ic magnetic resonance imaging and/orndovaginal ultrasound with Dopplermaging, and cerebral tomography or

agnetic resonance imaging.Patients are scored according to the

IGO classification 2000. High-risk GTNndergoes combination chemotherapy.19

In this article, we analyzed low-riskTN. The management met the FIGO

ecommendations for gynecologic can-er.20 Those with risk score � 6 werelassified as having low-risk GTN. Theyeceived single-agent MTX in a modifiedegimen of Bagshawe et al17: intramus-
ular MTX 1 mg/kg on days 1, 3, 5, and 7. W
43.e2 American Journal of Obstetrics & Gynecolo

olinic acid (calcium folinorate) wasiven per os at a dose of 10 mg on days 2,, 6, and 8. The regimen was repeatedfter a 7-day treatment window untilCG level normalized or either toxicityr resistance were diagnosed. SerumCG levels were measured weekly toonitor the response. As FIGO recom-ends, at least 2 courses of consolida-

ion chemotherapy were given beyondrst negative hCG level. Remission wasefined as a normal hCG level for 3 con-ecutive weeks. After biochemical remis-ion, hCG was monitored monthly for aear. A second chemotherapy protocolactinomycin-D given as a 5-day course0.5 mg intravenously] every 14 days) orhemotherapy combinations (etopo-ide, MTX, actinomycin-D– cyclophos-hamide [EMA]- vincristine [CO]) weresed when the response to MTX aloneas unsatisfactory.A complete blood cell count, alongith renal and liver function, was alsoeasured before starting the chemo-

herapy. Complete blood cell countsith platelet counts, as well as renal andepatic function tests, were then mea-ured every 2 weeks during the follow-uperiod. The criteria for hematologic andepatic toxicity were those of the Com-on Terminology Criteria for Adverse

vents (CTCAE) of the National Cancernstitute (NCI).21 All side effects wereoted. Patients were routinely askedbout the development of adverse eventsnd their response was noted in theirecords. Chemotherapy was postponedn cases of grade 3 or 4 toxicity.

Repeated curettage was used in thetandard management of some patients,hen there was heavy bleeding soon af-

er the initial evacuation, or when re-ained tissue (� 17 mm) was diagnosedn the uterine cavity on routine ultra-ound (8-10 days later). Surgical resec-ion was performed either for chemo-herapy-resistant disease or to treat acuteomplications, such as tumor hemor-hage and infection. Hysterectomy wasometimes performed to remove largeterine tumor burden.All statistical analyses were performed

sing SAS 9.1.3 Service Pack 3 (SAS In-titute, Inc, Cary, NC) and SPSS for

indows, version 12 (SPSS, Inc, Chi- 0

gy JUNE 2009

ago, IL) software. Normality of distri-utions was explored by Shapiro-Wilksesting. Differences in numeric data be-ween groups were tested nonparametri-ally (Mann-Whitney U test) or para-etrically (Student t test). All tests were

onsidered significantly different at P �05.

ESULTS

rom November 1999 through Decem-er 2006, 225 patients were treated in ourenter of which 2 had another tumor af-er a second pregnancy (227 tumors).

There were 3 placental site trophoblas-ic diseases, 31 high-risk GTN, and 193ow-risk GTN.

In all, 51 patients with low-risk GTNere excluded from this study: patientsho fulfilled 1 of the GTN criteria butho had hCG normalized after evacua-

ion and before any chemotherapy wastarted (n � 6); patients who already had

different single-agent chemotherapyrotocol than that used in our center (n

14) or combination chemotherapy (n14); and patients who had hCG nor-

alized after a hysterectomy (n � 17)ithout chemotherapy.The characteristics of the 142 patientsith a low-risk GTN included in this

tudy are displayed in Table 1. Six ofhese patients became pregnant beforending their 1-year hCG monitoring af-er remission. In all, 87 patients had aecond evacuation shortly after the firsturettage because of a sonographic re-ention in most cases. Second curettageas never an option at the time of diag-osing GTN.The overall remission rate after single-

gent MTX protocol was 77.5% (110 pa-ients). Of these, 108 patients (76.1%)chieved primary complete remissionhereas 2 patients (1.4%) had secondary

ecurrence after hCG normalization.he recurrence was successfully treatedith a hysterectomy for the first and a

econd-line multiple-agent chemother-py (EMA-CO) for the second, achievingfterward a complete remission. For thisroup, the mean time for hCG to nor-alize was 11.2 weeks (SD � 9.85; range,

.86-72.14). The mean number of MTX

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ourses needed to achieve remission was.3 (SD � 2.86; range, 1-18).In all, 32 patients (22.5%) required

econd-line chemotherapy. Two pa-ients required this change of treatmentecause of MTX toxicity (stomatitis ofhe oral cavity for both of them [grade 3f the CTCAE] with photosensitivitygrade 2 of the CTCAE] for 1). Thirty21.1%) of these had their chemotherapywitched after resistance to single-agent

TX. The second-line chemotherapyas EMA-CO for 18 patients, single-

gent actinomycin-D for 13 patients,nd actino-Vp 16 (actinomycin-D,espesid, or etoposide) for 1 patient.Only 2 of the 18 patients on EMA-CO

s the second-line treatment showed re-istance and required third-line chemo-herapy. One of them had complete re-

ission with etoposide, cisplatin (EP)-MA as third-line chemotherapy. A lateecurrence was successfully treated withhysterectomy. The second patient, wholready had her hysterectomy at the startf her treatment, eventually developedesistance even to the third-line chemo-herapy protocol (bleomycin � EP). Ce-ebral radiotherapy was begun after theiagnosis of cerebral metastasis. She diedweek later. Of the remaining 16 pa-

ients treated with EMA-CO with remis-ion, 3 patients had partial remission.heir recurrences were successfully

reated with third-line chemotherapyEMA-CO for 2 and bleomycin � EP)ith hysterectomy for 2 patients.Only 1 recurrence was noted in the 13

atients who had a remission with acti-omycin-D as the second-line treat-ent. She was successfully treated with

MA-CO and hysterectomy.The mean time for hCG to normalize

n patients resistant to MTX was 20.7eeks (SD � 7.28; range, 11.43-43.14).his was significantly longer than the

ime required of 11.2 weeks (SD � 9.85;ange, 0.86-72.14) in women whochieved complete remission with sin-le-agent MTX (P � .05). All patientsut 1 achieved remission and remainedisease free until the time of analysis. Theverall relapse rate was 4.9%. The meanollow-up time was 19.4 months (SD �
.89; range, 1.8-69.1).
Other than the 2 adverse events thate described above, no major side effectsere experienced. The criteria for hema-

ologic, renal, and hepatic toxicity wesed were those of CTCAE of the NCI.e were able to collect up to 85.2% of

he weekly blood test results of all pa-

TABLE 1Baseline characteristics of patientsgestational trophoblastic neoplasiaCharacteristic Mea

Age (y) 3...................................................................................................................

Gravida...................................................................................................................

Parity...................................................................................................................

Pretreatment hCG (IU/L) 3...................................................................................................................

Interval from index pregnancy(mo)...................................................................................................................

Interval from index pregnancy(mo)

�.........

.........

.........

� 1...................................................................................................................

FIGO stage I.........

II.........

III.........

IV...................................................................................................................

FIGO score �.........

.........

...................................................................................................................

Pulmonary metastasis...................................................................................................................

Cerebral metastasis...................................................................................................................

Hysterectomy...................................................................................................................

FIGO, International Federation of Gynecology and Obstetrics;Chalouhi. Methotrexate for 2000 FIGO low-risk GTN pat

TABLE 2Toxicity of 8-day methotrexate reg

VariableGrade 2(moderate)

Hemoglobin 14...................................................................................................................

Leukocytes 7...................................................................................................................

Platelets 0...................................................................................................................

Creatinine 0...................................................................................................................

ALT/AST 8...................................................................................................................

No. of patients 25...................................................................................................................

AE, adverse event; ALT, alanine aminotransferase; AST, aspa
Chalouhi. Methotrexate for 2000 FIGO low-risk GTN patient
JUNE 2009 Americ

ients during their follow-up. We couldot be exhaustive of all the tests as some

reating physician sometimes refrainedrom sending them to the reference cen-er when they revealed normal findings.ence, the exhaustivity criteria can be

onsidered as reached. The blood/bone

ith low-risk� 142)

SD Range

8.16 18.8-52.4..................................................................................................................

2.07 1-14..................................................................................................................

1.36 0-7..................................................................................................................

30 85,393 7.3-906,300..................................................................................................................

1.64 0-9.8

..................................................................................................................

84.5%..................................................................................................................

10.6%..................................................................................................................

2 4.9%..................................................................................................................

0%..................................................................................................................

84.5%..................................................................................................................

6.3%..................................................................................................................

9.2%..................................................................................................................

0%..................................................................................................................

54.9%..................................................................................................................

33.1%..................................................................................................................

12.0%..................................................................................................................

31.4%..................................................................................................................

0%..................................................................................................................

12.0%..................................................................................................................

, human chorionic gonadotropin; SD, standard deviation.s. Am J Obstet Gynecol 2009.

n

Grade 3(severe)

Grade 4 (life-threatening ordisabling AE)

0 1..................................................................................................................

1 0..................................................................................................................

0 1..................................................................................................................

0 0..................................................................................................................

4 0..................................................................................................................

4 2..................................................................................................................

aminotransferase.

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2.6.........

1.1.........

2,6.........

2.5

.........

4.........

4-6.........

7-1.........

2.........

.........

.........

.........

.........

2.........

3-4.........

5-6.........

.........

.........

.........

hCG

ime

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.........

.........

.........

.........

.........

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arrow toxicity and metabolic/labora-ory toxicity are reported in Table 2.here were 28 patients (19.7%) who had

oxicity with a CTCAE grade � 2, ofhich 6 patients (4.2%) had severe

grade � 3) toxicity. There were only 2ases of toxicity grade 4: 1 had hemoglo-in at 5.7 g/dL and the other a plateletount at 21,000/mm3. They resolvedithout any complication (after ade-uate treatment). No pulmonary toxic-

ty of this chemotherapy was noted inny patients. A 37-year-old patient,eavy smoker, had a stroke during herreatment, which was hence interrupted.er hCG level normalized spontane-

usly. The neurologic sequelae of thetroke partially regressed spontaneously.he patient kept a mild left hemiparesis.

t is difficult to confirm the imputabilityf chemotherapy.22

The mean pretreatment hCG level was1,948 IU/L (SD � 93,356; range, 7.3-06,300) in the group of patients whoere responders to single-agent chemo-

herapy, whereas it was 34,975.3 (SD �0,149.31; range, 180-222,121) for non-esponders. They were not significantlyifferent. Nevertheless, if we considerhe first group, there was 1 isolated valuef hCG that was extremely elevated906,300). If we remove this unique andsolated value, the mean pretreatmentCG level in the responders to single-gent chemotherapy was 23,927.1 (SD �0,651.81; range, 7.3-243,866). The dif-

TABLE 3Characteristics of responders andCharacteristic

Age (y)

...................................................................................................................

Pretreatment �-hCG (IU/L) (not corrected)

...................................................................................................................

Pretreatment hCG (IU/L) (corrected)

...................................................................................................................

Recurrence after normalization of hCG (%)...................................................................................................................

FIGO score (%)..........................................................................................................

� 3..........................................................................................................

� 4...................................................................................................................

FIGO, International Federation of Gynecology and Obstetrics;Chalouhi. Methotrexate for 2000 FIGO low-risk GTN pat

erence becomes statistically significant p


P � .05) between responders andonresponders.We compared the characteristics of

he patients who were successfullyreated with MTX with those of the

TX-resistant group. The significantifferences are summarized in Table 3.here was no statistical difference in the

ime from diagnosis to treatment be-ween these 2 groups.

OMMENThe most commonly reported outcomeeasure for the treatment of this disease

s effectiveness, defined as primary re-ponse, number of treatments to cure,umber of toxic events requiring ahange in treatment, relapse, and effec-iveness of secondary salvage.

The greater potential source of stressnd emotional trigger for these repro-uctive-aged women while being treated

or GTN is the failure of primaryreatment.23

Although the majority of studies de-ned remission as hCG level within theormal range for at least 3 consecutiveeeks, some, such as Bagshawe et al17

nd McNeish et al,24 required at least 6onsecutive weeks. The overall remis-ion rate after single-agent MTX proto-ol was of 77.5%, which is comparableith the results reported in literature

anging from 68-90%.1,4,10,11,16,25-31 Re-ently, Osborne32 presented, in an ab-tract, a 53.3% success rate of MTX com-

responders to 8-day methotrexate rResponders N

33.71 (SD � 7.81; range,16.8-52.4)

32

.........................................................................................................................

31,948 (SD � 93,356;range, 7.3-906,300)

3r

.........................................................................................................................

23,927.1 (SD � 40,651.81;range, 7.3-243,866)

3r

.........................................................................................................................

1.8 1.........................................................................................................................

.........................................................................................................................

81.8% 1.........................................................................................................................

62.5% 3.........................................................................................................................

, human chorionic gonadotropin; SD, standard deviation.s. Am J Obstet Gynecol 2009.

ared with a 69.4% success rate using s

gy JUNE 2009

actinomycin for low-risk GTN definedith the 2000 FIGO scoring system. Noirect comparison can be made betweenhese MTX results and those previouslyublished in the literature. Nevertheless,ne can wonder whether more intensiveTX schedules would lead to the same

tatistically different results betweenTX and dactinomycin.However, arguing in favor of a specificonochemotherapy certainly needs to

ake into account homogeneity of pa-ients at low risk included in the studies,efinition of failure, and dose intensityf treatment. Universal use of 2000IGO scoring system, as patiently advo-ated by Kohorn and Ngan,20 has beenhe first important step to homogeneousllocation of treatment. Reproducibleefinition of failure, as proposed, for ex-mple, by the Canadian Gynecologicncology Group study on dactinomycin

alvage therapy,33 will need to be the nexttep toward comparisons between treat-

ents. Finally, although theoretical ele-ents such as the number of cells in cycle

ould participate to favor 1 type of MTXegimen, no clinical confirmation of thisrinciple has ever been published andnly multicentric level 1 comparisons ofoses, schedules, and drugs will be theext step toward understanding the op-

imal first-line treatment. The results weisplay here, using the widely accepted000 FIGO score, will help calculate

menresponders P

5 (SD � 9.2; range,-51.4)

.04

..................................................................................................................

75.3 (SD � 50,149.31;e: 180-222,121)

..................................................................................................................

75.3 (SD � 50,149.31;e, 180-222,121)

� .05

..................................................................................................................

.007..................................................................................................................

..................................................................................................................

% .02..................................................................................................................

%..................................................................................................................

non egion

1.70.3

......... .........

4,9ang

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4,9ang

......... .........

5.6......... .........

......... .........

8.2......... .........

7.5......... .........

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The overall remission rate for low-riskTN was 99.9% as only 1 patient of thoseho required further treatment did not

chieve complete remission, and died af-er third-line polychemotherapy and ra-iotherapy. This supports the hypothesishat the overall survival in low-risk GTNs almost 100%.11,25,28,34

In addition to achieving long-termure, minimizing toxicity is an impor-ant factor in evaluating the treatment.oxicity grade 3 or 4 occurred in 4.2% ofll patients but none of these were lifehreatening. Only in 2 cases (1.4%) was itevere enough to impose change of che-

otherapy. Although Osborne anderulath11 clearly state that this regimen

s toxic, our rate is relatively low com-ared with many previous studies.1,27

onanont et al1 reported MTX toxicityn 19.2% of patients: mucositis (6.4%),epatotoxicity (6.4%), neutropenia3.2%), and thrombocytopenia (1.1%).erkowitz et al27 reported granulocyto-enia, thrombocytopenia, and hepato-oxicity in 5.9%, 1.6%, and 14.1% of pa-ients, respectively. Also, our toxicityate is relatively low compared witheekly intramuscular MTX: nausea8%, vomiting 10%, stomatitis and he-atologic disturbance (thrombocytope-

ia and/or granulocytopenia) 13%35,36

nd 5-day infusional MTX regimen.11,37

gain, our data can be used in the futureor evaluation of treatment toxicity inomogeneous groups of patients withisk defined according to the 2000 FIGOcoring system.

The statistically significant factors inhe current study that were associatedith response to single-agent MTX pro-

ocol in patients with low-risk GTN werehe age of the patient, her initial serumCG level, and the FIGO score. Patients

n whom initial therapy failed wereounger (33.7 years [SD, 7.81] for re-ponders vs 31.7 years [SD, 9.2]). Earliertudies did not all agree on the role of agen response to MTX, without any signif-

cant difference between results never-heless. Some authors suggested olderge tended to be a resistance factor15,30,38

hereas others found that maternal ageid not influence the development ofrug resistance.39 On the other hand,
ost studies agree with our result that d
igher pretreatment hCG levels andigher FIGO scores significantly in-reased the risk of failure.1,11,15,25,40,41

The only recurrence associated factordentified in this study (P � .04) was theIGO score with a recurrence rate of.7% and 12.5% with a score � 3 and �, respectively. Although Matsui et al39

nd Yang et al42 found a similar pattern,he latter identified 3 other recurrencessociated factors: an interval from indexregnancy of � 12 months, a negativelood hCG titer after 7 courses of che-otherapy, and � 2 courses of consoli-

ation chemotherapy. Chen et al40 alsoound the interval in months from indexregnancy to be significantly associatedith outcome of chemotherapy. We

ould not identify the same factors as ourean interval from index pregnancy was

.5 months (SD � 1.64; range, 0-9.8)nd all patients had their 2 consolidationourses. The case analysis of the only pa-ient who showed resistance and diedven after shift of chemotherapy and thetart of radiotherapy could not find anyf these factors and no other particularlement explaining her resistance.

Our recurrence rate was of 4.9%, com-atible with the overall recurrence rate of-8% reported in the literature.42,43

To date, there is no high-level evidencevailable in the literature to decide towitch MTX-resistant patients to dacti-omycin or EMA-CO. Data from Mc-eish et al24 from the United Kingdom

howed an 87% rate of success withactinomycin in 67 patients with GTNnd MTX resistance or toxicity (8-dayTX regimen). Nine patients needed a

witch to EMA-CO as third-line treat-ent and were finally cured. Impor-

antly, the median hCG level of their pa-ients was as low as 40 UI/L (range, 7-476I/L) and during the same time patientsith hCG level � 100 UI/L were usually

reated with second-line EMA-CO. Cov-ns et al33 then published a study whereactinomycin was accepted with higherCG levels (2 patients had hCG between0,000 and 34,000 UI/L but still 2 in 3atients had hCG � 1000 UI/L) in pa-ients with MTX resistance (type of MTXegimen not available). Success rate was4% in 38 evaluable patients. Again, all
actinomycin-resistant patients were fi- o
JUNE 2009 Americ

ally cured with third-line treatment.ogether, these very limited data allow to

witch to dactinomycin patients withTX-resistant GTN with serum hCG

evels � 1000 UI/L, without compromis-ng survival. Data for patients with hCGevels � 1000 UI/L are extremely limitednd should therefore be considered withaution. We can certify that single-agent

TX protocol has a good complete re-ission rate of 77.5% with low toxicity

evel in patients with low-risk GTN de-ned according to the 2000 FIGO scor-

ng system. Otherwise low-risk GTN hasn excellent global cure rate of 99.9%,llowing the patients to retain fertilitynd achieve remission. These data willllow comparison with future reports onTX treatment for low-risk GTN as the

IGO scoring/staging system is nowequired. f

CKNOWLEDGMENTSe would like to thank Touria Hajri for her valu-

ble contribution to this work. The authors alsohank Mona Sabra, MD, and Walid Saad, PhD.

EFERENCES. Tonanont M, Inthasorn P, Boriboonhirunsarn, et al. Response to initial treatment of low and

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Methotrexate for 2000 FIGO low-risk gestational trophoblastic neoplasia patients: efficacy and toxicity