Cervical Carcinoma                                                                                                                                       123                                     

 

20. Cervical Carcinoma

 

20.1        General considerations

International Federation of Gynecology and Obstertrics Staging for Cervical Carcinoma
Stage
0                        Carcinoma in situ, intraepithelial carcinoma
1                                              Carcinoma strictly confined to cervix ( may include extension to corpus)

        I A  1         Measured invasion of stroma is no deeper than 3 mm and no wider than 7 mm

        I A  2         Measured invasion of stroma is deeper than 3 mm but less than 5 mm and no wider

                           than 7 mm
II                         Carcinoma extends beyond cervix but not as far as pelvic wall. Involves vagina but

                            not so far as lower third

        II A             No obvious parametrial involvement

        II B              Obvious parametrial involvement

III                        Carcinoma extends  to pelvic side wall. On rectovaginal examination, there is no

                            cancer-free space between the tumor and the pelvic wall. Tumor involves lower

                            third of vagina. All cases with hydronephrosis or nonfunctioning kidney are

                             included unless they are known to be due to other causes.

        III A             No extension to pelvic wall, but lower third of vagina is involved

        III B             Any of the following: extension to pelvic wall, hydronephrosis,  or nonfunctioning

                             kidney

IV                         Carcinoma has extended beyond the true pelvis or has clinically involved the
                             mucosa of the bladder or rectum. Bullous edema alone does not permit a case to be
                             allotted to stage IV

        IVA              Spread of the growth to adjacent organs

        IVB              Spread to distant organs

           

            Squamous cell histology accounts for over 75% of the patients with cervical cancer.

 

Early stage cervical cancer is treated primarily by surgery and/or chemoradiotherapy, Chemoradiotherapy is also the mainstay of management for locoregional disease which has spread beyond  the cervix but is still confined to the pelvis and draining lymph node basins (stages IIB – IVA ), So far, the application of neoadjuvant chemotherapy prior to definitive surgery and/or radiotherapy has not shown a clearly positive effect on the overall outcome.

124                                                                                                                                     Cervical Carcinoma                                     

           

            Literature: for review e.g.

BLOSS, Curr, Oncol. Rep. 3 (2001): 33-40  (chemotherapy for advanced or recurrent

cervical cancer)

GREEN et al, Lancet 358 (2001): 781-786 (meta- analysis of concurrent chemoradiotherapy studies)

LEHMAN and THOMAS, Int. J. Gynecol. Cancer 11 (2001): 87 – 99 (concurrent  chemotadiotherapy for locally advanced cervical cancer)

ROSE , Eur. J. Cancer 38 (2002): 270 – 278 ( chemoradiotherajpy for cervical cancer)

TIERNEY et al, Eur. J. Cancer 35 (1999):  406 – 409 (meta – analysis of neoadjuvant chemotherapy for locally advanced cervical cancer)

 

20.2     Single agent chemotherapy

 

20.2.1 Cisplatin

Cisplatin                                      50 – 100 mg/m2                    i.v.                  d 1

            To be repeated every 3 weeks

 

            Literature:

                        ALBERTS et al, Semin, Oncol. 18 (Suppl 3) (1991): 11 – 24

 

20.2.2   Ifosfamide (with mesna uroprotection)

Ifosfamide                                      1200 – 1500 mg/m2            i.v.                    d 1-5 or

                                                                    5000 mg/m2           i.v.(24 h inf)     d 1

To be repeated every 3 weeks

 

Literature:

            COLEMAN et al, Br. J. Cancer 58 (1988): 283

            MEANWELL et al, Cancer Treat. Rep. 70 (1986) : 727 – 730

            SUTTON et al, Invest. New Drugs 7 (1989): 341 – 343

 

20.3        Combination chemotherapy

 

20.3.1 Cisplatin + ifosfamide

Cisplatin                                  50 mg/m2                         i.v.                           d 1

Ifosfamide                           5000 mg/m2                         i.v. (24 h inf)           d 1

                                                                                        With mesna uroprotection

To be repeated every 3 weeks (max 6 cycles)

 

Literature:

            OMURA et al, J. Clin. Oncol. 15 (1997) : 165 – 171

 

20.3.2 Carboplatin + ifosfamide

Carboplatin                           300 mg/m2                        i.v.                              d 1

Ifosfamide                           5000 mg/m2                         i.v. (24 h inf)           d 1

                                                                                        With mesna uroprotection

            To be repeated every 4 weeks

 

            Literature:

                        KUEHNLE et al, Cancer Chemother, Pharmacol. 26 (Suppl) (1990): 33 – 35

 

Cervical Carcinoma                                                                                                                                  125

 

20.3.3 BIP

Bleomycin                               30 mg                  i.v. (24 h inf)                              d 1

Cisplatin                                  50 mg                  i.v.                                              d 2

Ifosfamide                              5000 mg/m2          i.v. (24 h inf)                              starting on d 2

                                                                             With mesna uroprotection

To be repeated every 4 weeks

 

Literature:

            BUXTON et al, Acta Oncologica 27 (1988): 545-549  and J. Natl, Cancer Inst. 8

            (1989) : 359 – 361

            MEANWELL et al, Contr. Oncol, 26 (1987): 176- 192

20.3.4 TIP

Paclitaxel                                 175 mg               i.v. (3 h inf)                               d 1

Cisplatin                             50(-75) mg/m2         i.v.                                             d 2

Ifosfamide                                5000 mg/m2        i.v. (24 h inf)                            d 2

                                                                             With mesna uroprotection

           

            Literature:

                        ZANETTA et al, Ann. Oncol. 9 ( 1998): 977- 980  and Ann. Oncol. 10 (1999): 1171- 1174

 

20.3.5 Cisplatin + 5 – fluorouracil

See 20.4  * Concurrent chemoradiotherapy*

 

20.3.6 Cisplatin+ Paclitaxel

Paclitaxel                                     135 mg                  i.v. (24 h inf)                         d 1

Cisplatin                                  50 (-75) mg/m2          i.v.                                        d 2

To be repeated every 3 weeks

 

Literature:

            ROSE et al, J. Clin. Oncol. 17 (1999): 2676 – 2680

 

20.4        Concurrent chemoradiotherapy

Generally based on cisplatin with or without 5 – fluorouracil, e.g.

Author
Cisplatin

5- Fluorouracil
Hydroxyurea
To be repeated
Keys

et  al

40 mg/m2

(max 70 mg)

i.v.

 
 

Weekly x 6

Morris

et  al
75 mg/m2

i.v. d 1

1000 mg/m2 i.v.

(cont inf) d 1-4
 

every 3 wks

(x 2)

Peters

et  al
75 mg/m2

i.v. d 1

1000 mg/m2 i.v.

(cont inf) d 1-4
 

Every 3 wks

(x 4), RT given

with cycles 1+2

Rose

et  al
50 mg/ m2
i.v.* d 1
 
 
 

1000 mg/m2 i.v.*

(cont inf) d 1-4
2 mg/m2 p.o.

* every 3 wks

(x 2), HU  given

twice weekly for

6 weeks

Whitney

et  al
50 mg/m2

i.v. d 1

1000 mg/m2 i.v.

(cont inf) d 1-4
 

Every 3 wks

(x 2).

Total dose and technique of application of pelvic irradiation varied between studies  and stages.

 

 

126                                                                                                                                     Cervical Carcinoma                                     

 

            Literature:

                        KEYS et al, N. Engl. J. Med. 340 (1999) : 1154 – 1161 (GOG protocol 123, bulky stage IB)

MORRIS et al, N. Engl. J. Med. 340 (1999): 1137 – 1143 (RTOG protocol 9001, stages IB or IIA with invasion of pelvic lymph nodes or tumors ≥ 5 cm in diameter and IIB- IVA)

PETERS et al, J. Clin. Oncol. 18 (2000): 1606 – 1613  (SWOG protocol 8797, stages IA2, IB, and  IIA)

ROSE et al, N. Engl. J. Med. 340 (1999): 1144–1153 (GOG protocol 120, stages IIB – IVA )

WHITNEY et al, J. Clin. Oncol. 17 (1999): 1339 – 1348 (GOG protocol 85/SWOG protocol 8695, stages IIB – IVA)

 

20.5        Non-squamous cell histology

(Mainly adenocarcinoma and adenosquamous carcinoma)

 

There is a relative lack of effective chemotherapeutic agents available to treat non-squamous carcinoma of the cervix . Single agents with reported activity include cisplatin, paclitaxel, and ifosfamide.

 

Literature:

            CURTIN et al, J. Clin. Oncol. 19 (2001): 1275-1278 (paclitaxel)

            SUTTON et al, Gynecol. Oncol. 47 (1993): 48 – 50 (ifosfamide)

            THIGPEN et al, Cancer Treat. Rep. 70 (1986): 1097 – 1100 (cisplatin)