156                                                             Gestational Trophoblastic Disease / Gestational Choriocarcinoma

 

27.                              Gestational Trophoblastic Disease/

Gestational Choriocarcinoma

 

27.1        General considerations

 

Anatomic FIGO staging system for gestational trophoblastic disease*
Stage I               Disease confined to the uterus
Stage II              Disease outside of uterus but is limited to the genital structures
Stage III             Disease extends to the lungs with or without known genital tract

                           involvement
Stage IV             All other metastatic sites

           *     There is no accounting in the FIGO staging system for hydatidiform mole

 

The scoring system for FIGO 2000 staging/scoring
FIGO score             0                            1                         2                    4 points

Age                           ≤39                     >39                           

Antecedent               Hydatidiform     Abortion            Term

pregnancy                 mole                                              pregnancy 

Interval months         <4                    4 – 6                   7 – 12                   > 12

from index             

pregnancy

Pretreatment              < 103               103 – 104             >104 – 105               >105

hCG IU/ ml

Largest tumor              3 – 4 cm          ≥ 5 cm

size including uterus

Site of                                                   Spleen                Gastrointes-        Brain

metastases                                            Kidney               tinalf tract            Liver

N 0 of metastases          0                      1 – 4                    4 – 8                   > 8

Identified

Previous failed                                                               Singel drug           Two or

chemotherapy                                                                                                 more

                                                                                                                        drugs

           

Gestational trophoblastic disease is a highly curable condition, even in the presence of  windespread metastases. The intensity of systemic treatment varies from partial hydatidiform mole which infrequently requires chemotherapy, to gestational choriocarcinoma for which multiagent chemotherapy is the standard treatmet.

 

            Literature: for review e.g.

                   COHN and HERZOG, Curr. Opin. Oncol. 12 (2000): 492 – 495

                   NEWLANDS et al, Hematol. Oncol. Clin. North Am. 13 (1999): 225 – 244

                   SCHORGE et al, J. Reprod. Med. 45 (2000): 692 – 700

 

27.2     Low-risk group (score ≤ 6)

 

27.2.1 Methotrexate

Methotrexate                0.4 – 0.6 mg/kg      i.m. or i.v. (bolus)            d 1 – 5

To be repeated starting day 12 – 14. Until normalization of ß – hCG levels followed by another two courses as a safely margin.

 

 

Gestational Trophoblastic Disease / Gestational Choriocarcinoma                                                              157

 

            Literature:

                        HAMMOND et al, Am. J. Obstet. Gynecol. 98 (1967) : 71 – 78

            or

           

Methotrexate                   100 mg/m2              i.v. (30 min inf)               d 1 and

                                         200 mg/m2             i.v. (12 h inf)                   d 1

            Folinic acid was only given when the serum methotrexate level reached 10 µmol /l.

            Dactinomycin was added in patients not in complete response.

 

            Litetature:

                        WONG et al, Am. J. Obstet. Gynecol. 183 (2000): 1579 – 1582

 

27.2.2.                       Methotrexate + folinic acid

Methotrexate                    1 mg /kg               i.m. or i.v. (bolus)           d 1, 3, 5, 7

                                      (max 70 mg)

Folinic acid                      0.1 mg/kg              i.m.                                 d 2, 4, 6, 8

To be repeated starting day 15 – 18 . Until normalization of ß- hCG levels, followed by another 2 courses as a safety margin.

           

            Literature: e.g.

GLEESON et al, Eur. J. Gynaecol. Oncol. 14 (1993): 461 -  465 (weekly methotrexate compared with 8 – day methotrexate and folinic acid)

 

27.2.2 Dactinomycin

Dactinomycin                    10 – 12 µg/kg                    i.v. (bolus)           d 1 – 5 or

                                           1.25 mg/m2                        i.v. (bolus)          d 1 - 5       

            To be repeated every 2 weeks

 

            Literature: e.g.

                        OSATHANONDH et al, Cancer 36 (1975): 863 – 866

 

27.3.      High-risk group (score ≥ 7)

 

27.3.1 EMA – CO

Course 1

Etoposide                          100 mg/m2                   i.v. ( 1 h inf)               d 1 + 2

Methotrexate                     100 mg/m2                   i.v.                              d 1 and

                                           200 mg/m2                  i.v. (12 h inf)              d 1

Dactinomycin                    0.5 mg                         i.v. (bolus)                  d 1+2

Folinic acid                         15 mg/m2                    b.i.d. p.o. or i.m.

                               For 4 doses, beginning 24 h after the first MTX dose every 6 h

 

Cours 2

Vincristine                        1.0 mg/m2                      i.v. (bolus)                 d 8

Cyclophosphamide           600 mg/m2                     i.v. (30 min inf)         d 8

 

Course 1 and 2 are repeated in 6- day sequences ( unless mucositis develops ) up  to CR or resistance,  As a prophylactic treatment of the skull, intrathecal administration of 12.5 mg methotrexate on day 1 of course 2 (i.e. every alternate course).

 

 

158                                                             Gestational Trophoblastic Disease / Gestational Choriocarcinoma

 

            Literature:

                        BOWER et al, J. Clin. Oncol, 15 (1997):  2636 – 2643

                        SCHINK et al, Obstet. Gynecol. 80 (1992): 817 – 820

                        SURWIT and CHILDERS, J. Reproduct. Med. 36 (1991): 45 – 48

 

27.3.2 MAC

Methotrexate                 0.3 mg/kg                    i.m. (bolus)                d 1 – 5

Dactinomycin                8 – 10 µg/lg                 i.v. (bolus)                 d 1 – 5

Chlorambucil                 0.2 mg/kg                    p.o.                            d 1 – 5 or

Cyclophosphamide        250 mg                         i.v. (bolus)                d 1 – 5

To be repeated every 15 – 21 days.

 

Literature:

            LURAIN and BREWER, Obstet. Gynecol. 65 (1985): 830 – 836

 

27.4        Salvage therapy

 

27.4.1 EA (for low-risk disease)

Etoposide                        100 mg/m2                   i.v. ( 1 h inf)                   d 1 – 3

Dactinomycin                  0.5 mg/m2                    i.v. (bolus)                     d 1 – 3

To be repeated after a 7 – day break. Continued for 8 week.

 

Literature:

            DOBSON et al, Br. J. Cancer 82 (2000):  1547 – 1552

 

27.4.2 EP/EMA (for high-risk disease)

EP

Etoposide                        150 mg/m2                   i.v. (30 min  inf)              d 1

Cisplatin                     3 x  25 mg/m2                  i.v. ( 4 h inf)                     d 1

 

EMA

Etoposide                  100 mg/m2             i.v. (30 min inf)              d 1

Methotrexate             300 mg/m2             i..v.(12 h inf)                  d 1

Dactinomycin            0.5 mg                   i.v. (bolus)                      d 1

Folinic acid               15 mg                    b.i.d. p.o. or i.m.            d 2+3 (24 h after

                                                                                                       start of MTX)

 

EP and EMA are alternated at weekly intervals.

 

Literature:

            NEWLANDS et al, J. Clin. Oncol. 18 (2000):  854 – 859