Sananes C, Giaroli A, Soderini A, Guardado N, Snaidas L, Bermudez A, Ferreira M, di Paola G, Sardi J
Gynecologic Oncologic Unit, 1st Clinic of Gynecology, Buenos Aires University Hospital, Argentina.
Eur J Gynaecol Oncol. 1998;19(4):368-73.
The aim of the study was to determine if ACH given after NCH followed by RH could decrease the incidence of distant metastases in patients with locally advanced carcinoma of cervix uteri.
56 pts (34 Ib, 18 IIb, 4 IIIb) with confirmed diagnosis of squamous cervical cancer were enrolled in this phase II trial. The methodology used 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 courses with 10 days interval); 4) Clinical and sonographic tumor response evaluation following U.I.C.C. response criteria; 5) Radical hysterectomy; 6) Pathological risk factor evaluation; 7) ACH with P.M.C. (cis-platinum 50 mg/m2, methotrexate 30 mg/m2, cyclophosphamide 500 mg/m2) 3 courses every 21 days; 8) Comparison and location of recurrences with a neoadjuvant group (NCH + RH + RT to whole pelvis), and with a control group treated with conventional radiotherapy were done. For statistical analysis the Chi-Square was used and D.F.S. and overall survival (O.S.) were calculated according to the Kaplan Meier and Log Rank Test.
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 recurrences 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 recurrences). 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 pelvic and 1 distant) for tumors > 2 cm. (p<0.01 for pelvic recurrences). For the stage Ib with residual tumor <2 cm (n=14) there were no pelvic recurrences and only 1 distant. Comparing for Stage Ib with previous tumor volume >4 cm of the ACH Group (n=17) with a classical NCH (n=51) and control (n=51) groups, there were observed 2 (11.7%) pelvic and 1 (5,8%) distant relapses for the 1st Group, 3 (5.9%) pelvic and 3 (5.9%) distant relapses for the 2nd, and 11 (21.6%) pelvic and 5 (9.8%) distant relapses for the 3rd Group. From the comparison of locally advanced tumors (Stages IIb + IIIb) of ACH group (n=22), with a Stage IIIb surgically removed of classical NCH group (n=38) and with a control group of conventional RT (n=51), there were observed 6 (27%) pelvic and 1 (4.5%) distant relapses for the 1st Group, 4 (11%) pelvic and 7 (18.4%) distant relapses for the 2nd, and 31 (60.7%) pelvic and 5 (9.8%) distant for the 3rd one.
ACH after NCH + RH could be used for stage Ib with tumor volume > 4 cm, with complete clinical response or residual tumor < 2 cm. The results of this group of tumors suggest the importance of going on phase III trials comparing NCH+RH alone vs. NCH+RH+ACH. ACH could also be used to try to obtain better control of distant metastases in Stages IIb and IIIb. In these cases radiotherapy to the whole pelvis must not be excluded.
本研究旨在确定新辅助化疗（NCH）后行根治性子宫切除术（RH）再给予辅助化疗（ACH）是否能降低局部晚期子宫颈癌患者远处转移的发生率。
56例经确诊的鳞状宫颈癌患者（34例Ib期、18例IIb期、4例IIIb期）纳入本II期试验。采用的方法为：1）国际妇产科联盟（FIGO）临床分期；2）超声测定肿瘤体积＜或＞4cm；3）V.B.P.方案：顺铂50mg/m²，第1天；长春新碱1mg/m²，第1天；博来霉素25mg/m²，第1 - 2 - 3天（共3个疗程，间隔10天）；4）按照国际抗癌联盟（UICC）反应标准进行临床和超声肿瘤反应评估；5）根治性子宫切除术；6）病理危险因素评估；7）每21天给予3个疗程的含顺铂（50mg/m²）、甲氨蝶呤（30mg/m²）和环磷酰胺（500mg/m²）的ACH；8）与新辅助治疗组（NCH + RH + 全盆腔放疗）以及接受传统放疗的对照组比较复发情况及复发部位。统计分析采用卡方检验，无病生存期（DFS）和总生存期（OS）根据Kaplan - Meier法和对数秩检验计算。
中位随访75个月（范围42 - 108个月），Ib期患者的OS为88%，IIb期为78%，IIIb期为50%。复发情况如下：Ib期复发率为12%（4/34）（3例局部复发和1例远处复发）；IIb期为28%（5/18）（4例盆腔复发和1例远处复发）；IIIb期为50%（2/4）（2例盆腔复发）。手术标本中残留肿瘤体积＜2cm的患者（n = 39）有4例复发（3例盆腔复发和1例远处复发），残留肿瘤＞2cm的患者有7例复发（6例盆腔复发和1例远处复发）。（盆腔复发p＜0.01）。对于残留肿瘤＜2cm的Ib期患者（n = 14），无盆腔复发，仅1例远处复发。将ACH组中既往肿瘤体积＞4cm的Ib期患者（n = 17）与经典NCH组（n = 51）和对照组（n =
