NEOADJUVANT CHEMOTHERAPY FOLLOWED BY RADICAL HYSTERECTOMY AND POSTOPERATIVE ADJUVANT CHEMOTHERAPY IN THE TREATMENT OF CARCINOMA OF THE CERVIX UTERI - LONG-TERM FOLLOW-UP OF A PILOT-STUDY

Objective: The aim of the study was to determine if ACH given after NC H followed by RH could decrease the incidence of distant metastases in patients with locally advanced carcinoma of cervix uteri. Material: 5 6 pts (34 Ib, 18 IIb, 4 IIIb) with confirmed diagnosis of squamous cer vical cancer were enrolled in this phase II trial. The methodology use d was: 1) Figo clinical staging; 2) Ultrasonographic determination of tumor volume in < or > 4 cms; 3) V.B.P. scheme: cis-platinum 50 mg/m2/ day 1; vincristine 1 mg/m2/day 1; bleomycin 25 mg/m2/days 1-2-3 (3 cou rses with 10 days interval); 4) Clinical and sonographic tumor respons e evaluation following U.I.C.C. response criteria; 5) Radical hysterec tomy; 6) Pathological risk factor evaluation; 7) ACH with P.M.C. (cis- platinum 50 mg/m(2), methotrexate 30 mg/m(2), ciclophosfamide 500 mg/m (2)) 3 courses every 21 days; 8) Comparison and location of recurrence s with a neoadjuvant group (NCH+RH+RT to whole pelvis), and with a con trol group treated with conventional radiotherapy were done. For stati stical analysis the Chi-Square was used and D.F.S. and overall surviva l (O.S.) were calculated according to the Kaplan Meier and Log Rank Te st. Results: After a median follow-up of 75 months (range 42-108), O.S . for stage Ib was 88%, Stage IIb 78%, and 50% for IIIb. The recurrenc es were 12% (4/34) for Stage Ib (3 local and 1 distant); 28% for IIb ( 5/18) (4 pelvic and 1 distant); 50% (2/4) for IIIb, (2 pelvic recurren ces). When residual tumor volume was <2 cm in the surgical specimen (n =39) there were 4 recurrences (3 pelvic and 1 distant), and 7 (6 pelvi c and 1 distant) for tumors >2 cm. (p<0.01 for pelvic recurrences). Fo r the stage rb with residual tumor <2 cm (n=14) there were no pelvic r ecurrences and only 1 distant. Comparing for Stage Ib with previous tu mor volume >4 cm of the ACH Group (n=17) with a classical NCH (n=51) a nd control (n=51) groups, there were observed 2 (11.7%) pelvic and 1 ( 5,8%) distant relapses for the 1(st). Group, 3 (5.9%) pelvic and 3 (5. 9%) distant relapses for the 2(nd), and 11 (21.6%) pelvic and 5 (9.8%) distant relapses for the 3(rd). Group. From the comparison of locally advanced tumors (Stages IIb + IIIb of ACH group (n=22), with a Stage mb surgically removed of classical NCH group (n=38) and with a control group of conventional RT (n=51), there were observed 6 (27%) pelvic a nd 1 (4.5%) distant relapses for the 1(st) Group, 4 (11%) pelvic and 7 (18.4%) distant relapses for the 2(nd), and 31 (60.7%) pelvic and 5 ( 9.8%) distant for the 3(rd) one. Conclusion: ACH after NCH+RH could be used for stage Ib with tumor volume > 4 cm, with complete clinical re sponse or residual tumor < 2 cm. The results of this group of tumors s uggest the importance of going on phase III trials comparing NCH+RH al one vs. NCH+RH+ACH. ACH could also be used to try to obtain better con trol of distant metastases in Stages IIb and IIIb. In these cases radi otherapy to the whole pelvis must not be excluded.