Benedetti-Panici P, Greggi S, Scambia G, Salerno M G, Amoroso M, Maneschi F, Cutillo G, Caruso A, Capelli A, Mancuso S
Department of Obstetrics and Gynecology, Università Cattolica del S. Cuore, Medical School, Rome, Italy.
Gynecol Oncol. 1996 Apr;61(1):44-9. doi: 10.1006/gyno.1996.0094.
The increased frequency and poor prognosis of cervical adenocarcinoma call for new therapeutic strategies, especially in locally advanced disease. Combined neoadjuvant chemotherapy (NACT)-radical surgery (RS) has been investigated to assess its feasibility and the possible impact on disease outcome. Data were pooled from three consecutive trials on a total of 42 patients with FIGO Stage IB-IIA >4 cm (9), IIB (19), and IIIB (14) cervical adenocarcinomas. NACT regimens consisted of cisplatin (P), bleomycin (B) and methotrexate, high-dose PB, and P and doxorubicin combinations for one to three cycles. Responding patients underwent RS while those still ineligible for RS underwent radiotherapy. Fisher and chi squared tests were used to detect significant factors affecting response to NACT. Cox multivariate regression analysis was used to evaluate parameters affecting response and survival. Medians and life tables were computed by the method of Kaplan and Meier. Median follow-up times were 56 (17-95) and 54 months (15-92) from enrollment and RS, respectively. NACT-induced toxicity was generally mild and did not compromise RS when indicated. The 33 (79%) responders underwent laparotomy, while the 9 nonresponders received radiotherapy. RS was feasible in 29 (69%) patients. Macroscopic intraperitoneal tumor (IPT) excluded abandoning RS in 4 cases. Mild to moderate RS-related complications were seen in 41% of cases with the same pattern as in the absence of any prior treatment. In patients undergoing RS, node metastasis and microscopic IPT were detected in 2 (7%) and 3 (10%) patients, respectively. The 5-year overall and disease-free survivals were 71% (100% IB-IIA and 84% IIB vs 36% IIIB; P = 0.001) and 88%, respectively. None of the nonresponders survived (median 10 months, 6-25), compared with an 84% 5-year survival of responders (P < 0.001). FIGO stage and parametrial involvement significantly predicted response to NACT which was the only independent variable affecting survival (P = 0.006). This retrospective study provided evidence of the chemosensitivity of locally advanced cervical adenocarcinoma and that chemoresponsiveness is the most potent predictor of cure, as demonstrated in squamous cell cervical cancer. Combined NACT and RS is a feasible treatment which seems to be able to improve the outcome of Stage IB-IIB cervical adenocarcinoma. Randomized trials comparing this new strategy with conventional treatments seem to be warranted.
宫颈腺癌发病率的增加及其不良预后促使人们寻求新的治疗策略，尤其是针对局部晚期疾病。联合新辅助化疗（NACT）-根治性手术（RS）已被研究，以评估其可行性以及对疾病预后的可能影响。数据来自三项连续试验，共纳入42例国际妇产科联盟（FIGO）分期为IB-IIA期＞4 cm（9例）、IIB期（19例）和IIIB期（14例）的宫颈腺癌患者。NACT方案包括顺铂（P）、博来霉素（B）和甲氨蝶呤、高剂量PB以及P与阿霉素联合，疗程为1至3个周期。有反应的患者接受RS，而仍不符合RS条件的患者接受放疗。采用Fisher检验和卡方检验来检测影响NACT反应的显著因素。使用Cox多因素回归分析来评估影响反应和生存的参数。采用Kaplan-Meier法计算中位数和生命表。从入组和RS开始计算的中位随访时间分别为56个月（17 - 95个月）和54个月（15 - 92个月）。NACT引起的毒性一般较轻，在有指征时不影响RS。33例（79%）有反应的患者接受了剖腹手术，而9例无反应者接受了放疗。29例（69%）患者可行RS。4例因肉眼可见的腹腔内肿瘤（IPT）未放弃RS。41%的病例出现轻至中度与RS相关的并发症，其模式与未接受任何先前治疗时相同。在接受RS的患者中，分别有2例（7%）和3例（10%）检测到淋巴结转移和微小IPT。5年总生存率和无病生存率分别为71%（IB-IIA期为100%，IIB期为84%，IIIB期为36%；P = 0.001）和88%。无反应者均未存活（中位生存期10个月，6 - 25个月），而有反应者5年生存率为84%（P < 0.001）。FIGO分期和宫旁受累显著预测了对NACT的反应，而NACT反应是影响生存的唯一独立变量（P = 0.006）。这项回顾性研究提供了局部晚期宫颈腺癌化疗敏感性的证据，并且正如在宫颈鳞状细胞癌中所证明的那样，化疗反应性是治愈的最有力预测指标。联合NACT和RS是一种可行的治疗方法，似乎能够改善IB-IIB期宫颈腺癌的预后。比较这种新策略与传统治疗方法的随机试验似乎是必要的。
