Intra-arterial Chemotherapy with Cisplatin Followed by Radical Radiotherapy for Locally Advanced Cervical Cancer

Locally advanced cervical cancer has a dismal prognosis, with a high local failure rate and a poor survival rate. To improve the cure rate for advanced carcinoma of the cervix, we initiated a study of intra-arterial (I-A) chemotherapy with cisplatin via the uterine artery prior to definitive radiotherapy. I-A chemotherapy via the internal iliac artery has been used to treat advanced cervical cancer; however, access by way of the uterine artery has not been tested for this purpose. Thirty-four patients with central tumor ≥5 cm in anteroposterior diameter observed on CT scans were treated with I-A chemotherapy. I-A chemotherapy consisted of unilateral catheterization of the uterine artery using 120 mg/m²cisplatin. After assessment of I-A chemotherapy, all but 3 patients were treated with a combination of whole-pelvis external irradiation and intracavitary irradiation. The 3 patients underwent external radiotherapy alone. Twenty-seven of 34 patients treated were evaluable for response to I-A chemotherapy. Eleven patients (41%) experienced a partial response. Seventy-six percent of the 34 patients treated with I-A chemotherapy followed by radiotherapy exhibited a complete response by the end of treatment. Toxicity was well tolerated and no death due to treatment occurred. The 2- and 5-year actuarial survival rates were 64 and 55%, respectively. The crude incidences of pelvic recurrence and distant metastasis observed at a median follow-up of 54 months were both 47%. This study for locally advanced cervical cancer suggests there is benefit to be derived from our I-A chemotherapy followed by radical radiotherapy.     

奥沙利铂、顺铂分别联合多西他赛用于局部晚期宫颈癌根治术前新辅助化疗的临床研究

目的:比较奥沙利铂(OXA)联合多西他赛(DTX)与顺铂(DDP)联合DTX用于Ⅰ B2～ⅡB期局部晚期宫颈癌患者行根治性手术前新辅助化疗的疗效和毒副反应.方法:选择2009年2月至2010年12月江西省人民医院收治的Ⅰ B2～ⅡB期局部晚期宫颈癌患者65例,随机分为研究组(35例)和对照组(30例).研究组采用OT方案(OXA 130 mg/m2+ DTX 75 mg/m2);对照组采用PT方案(DDP 60 mg/m2+ DTX 75 mg/m2),每组在根治性子宫切除术前各行新辅助化疗2个周期,并比较两组新辅助化疗的疗效、毒副反应及术后切除子宫标本的病理组织检查情况.结果:①研究组化疗的有效率(97.1％)与对照组(96.7％)比较,差异无统计学意义(P＞0.05).②新辅助化疗毒性反应:研究组WBC减少(Ⅱ度)发生率(5.7％)和N减少(Ⅱ度)发生率(15.7％)均低于对照组(18.3％和31.7％)(P＜0.05);研究组脱发、恶心呕吐和肾脏毒性反应(Ⅰ度和Ⅱ度)发生率均明显低于对照组(P＜0.05);研究组外周神经毒性反应率(Ⅰ度和Ⅱ度)(28.6％和20.0％)均明显高于对照组(6.7％和0)(P＜0.05).③两组术后标本病理组织检查:病理完全缓解率和理想的病理反应率及宫颈间质浸润、宫旁浸润、外科切缘阳性率等方面比较,差异均无统计学意义(P＞0.05).结论:OXA+DTX与DDP+ DTX两种新辅助化疗方案对局部晚期宫颈癌均有明显效果,OXA+ DTX方案总体毒性反应低于DDP+ DTX方案,明显改善患者在化疗期间的生活质量.     

Long-term Quality of Life and Sexual Function After Neoadjuvant Chemotherapy and Radical Surgery for Locally Advanced Cervical Cancer

BackgroundCervical cancer survivors report the worst quality of life (QoL) among all cancer survivors and this is mainly due to their younger age and the long-term treatment sequelae.AimThe purpose of this study is to assess the long-term QoL and sexual function of locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemotherapy (NACT) and radical hysterectomy (RH) instead of the standard chemoradiotherapy.MethodsThis is a retrospective case-control study including LACC patients (FIGO stage IIB-IVA) treated with the NACT-RH strategy and a control group of healthy women undergoing hysterectomy for uterine fibromatosis in the same period.OutcomesMain outcome measures were the EORTC QLQ-C30 and EORTC QLQ-CX24 for quality of life and Female Sexual Function Index (FSFI) for sexual function.ResultsOverall, 96 patients were included: 48 LACC and 48 controls. The mean age at diagnosis was 45.5 ± 9.0 and 47.0 ± 7.8, respectively (P = .38). Compared to controls, LACC patients reported lower mean scores for the global health status (69.4 ± 22.6 vs 81.2 ± 24.3; Mean Difference (MD): -11.80 [95% CI: -21.19, -2.41]; P = .016), QLQ-C30 functional scale (80.1 ± 22.6 vs 92.4 ± 14.9; MD: -12.30 [95% CI: -19.96, -4.64]; P = .002), QLQ-Cx24 functional scale (55.5 ± 25.0 vs 80.4 ± 22.4; MD: -24.00 [95% CI: -34.40, -15.40]; P < .001), and the total FSFI (19.3 ± 9.6 vs 26.2 ± 9.9; MD: -6.90 [95% CI: -10.80, -3.00]; P < .001). On the other hand, LACC patients reported higher mean scores on the QLQ-C30 (16.9 ± 22.1 vs 8.4 ± 16.6; MD: 8.50 [95% CI: 0.68, 16.32]; P = .03) and QLQ-CX24 (26.0 ± 28.8 vs 15.0 ± 11.7; MD: 11.00 [95% CI: -2.21, 19.79]; P = .01) symptoms scales.Clinical implicationsThe confirmed poor quality of life even in surgically treated LACC survivors underlines the importance of tailoring parametrectomy based on lymph node status and developing personalized strategies.Strengths and limitationsThe study assessed the long-term QoL and sexual function in the specific subpopulation of LACC patients treated with NACT-RH. Main limitations include the small sample size and the retrospective design.ConclusionLACC long-term survivors treated with NACT-RH experience poor QoL and sexual dysfunction.Palaia I, Santangelo G, Caruso G, et al. Long-term Quality of Life and Sexual Function After Neoadjuvant Chemotherapy and Radical Surgery for Locally Advanced Cervical Cancer. J Sex Med 2022;19:613–619.     

Intense Neoadjuvant Chemotherapy with Cisplatin and Epirubicin for Advanced or Bulky Cervical and Vaginal Adenocarcinoma

Twenty-two consecutive patients with bulky or locally advanced cervical or vaginal adenocarcinoma were treated with a neoadjuvant chemotherapy regimen consisting of nine weekly courses of cisplatin (50 mg/m²) and three courses of epirubicin (70 mg/m²) at Weeks 1, 4, and 7, followed by radical hysterectomy. Salvage radiotherapy was administered to inoperable patients, whereas postoperative treatment with irradiation or further chemotherapy was given to those with detection of risk factors at surgery. Three patients (14%) did not complete the planned courses of chemotherapy (one refused after the first administration, one had severe myelotoxicity, and one had severe nephrotoxicity). Twenty-one subjects received at least four courses of treatment and were therefore evaluable for response. We observed 4 clinically complete and 10 partial responses, accounting for an objective response rate of 67%. Eighteen subjects (82%) underwent surgery without serious complications. No histopathologic complete response was observed. The response rate is in the lower range observed with other regimens for squamous cell carcinoma. Although feasible, this regimen implies a significant risk of myelotoxicity. This enhanced toxicity may be justified only if balanced by long-term survival.     

宫颈癌的术前介入治疗

近年来,宫颈癌的术前介入治疗愈来愈受到重视.本文就术前介入治疗的临床意义、介入治疗的药物选择、化疗的疗程及间隔、疗效的评价以及介入加手术的远期效果等方面进行探讨.     

同步放化疗与新辅助化疗术前用药在局部中晚期宫颈癌治疗中的临床疗效评价

目的:比较同步放化疗与新辅助化疗术前用药在治疗局部中晚期宫颈癌的临床疗效。方法:选择2002年3月至2005年3月我院收治的42例ⅠB2～ⅡB期宫颈癌患者,其中21例同步放化疗,21例新辅助化疗。两组化疗方案相同,鳞癌:顺铂(DDP)+博来霉素;腺癌:DDP+5-氟尿嘧啶(5-Fu)+丝裂霉素(MMC)。同步放化疗组化疗期间配合放疗,采用腔内近距离放疗。同步放化疗、新辅助化疗结束后选择合适时间手术。观察两组间的近期疗效、手术率及手术切缘阴性情况、毒副反应、远期疗效(1、3、5年生存率)。结果:两组间近期疗效差异无统计学意义(P>0.05)、手术率及手术切缘阴性率差异有高度统计学意义(P<0.01)。血液和胃肠道毒副反应差异无统计学意义(P>0.05),晚期并发症放射性直肠炎和膀胱炎差异有高度统计学意义(P<0.01)。1年、3年生存率差异无统计学意义(P>0.05),而5年生存率同步放化疗组高于新辅助化疗组(P<0.05)。结论:同步放化疗术前用药治疗局部中晚期宫颈癌优于新辅助化疗。     

新辅助化疗对晚期卵巢癌治疗应用价值的评估及多因素分析

目的:对晚期卵巢癌患者采用新辅助化疗的应用价值进行评估,及探讨新辅助化疗后间歇性肿瘤细胞减灭术满意缩瘤的标准。方法:回顾性研究2005年1月1日至2010年12月31日在四川大学华西第二医院住院治疗的晚期卵巢癌患者339例。比较225例接受初始肿瘤细胞减灭术及术后行辅助化疗(PDS组)和114例新辅助化疗联合间歇性肿瘤细胞减灭术(IDS组)患者的手术、围手术期并发症、无进展生存期(PFS)及总生存期(OS)。采用单因素和多因素分析晚期卵巢癌患者预后的独立因素,以及独立因素与晚期卵巢癌患者的临床及病理学特征与治疗方案选择间的关系。结果:1两组患者肿瘤细胞减灭术达到满意缩瘤的几率比较,差异无统计学意义(P0.05)。但IDS组肿瘤细胞减灭术达到无肉眼残留病灶比例(39.47%)高于PDS组(27.56%)(P0.05)。2IDS组术中出血量更少、输血比例更小、手术范围更小、手术时间更短、住院时间更短,差异有统计学意义(P0.05)。3两组的PFS和OS比较差异无统计学意义(P0.05)。多变量Cox回归分析结果患者肿瘤细胞减灭术后残留病灶大小(P0.001)、FIGO分期(P0.001)和年龄(P=0.003)是影响晚期卵巢癌患者OS的独立因素。4IDS组术后仅无肉眼残留病灶可提高患者的OS。FIGO分期与治疗方案选择间的关系有统计学意义(P=0.01),最大原发肿瘤直径与Ⅳ期卵巢癌患者治疗方案选择间的关系有统计学意义(P=0.07),通过STEPP分析,原发肿瘤直径的界值为8.6 cm。结论:新辅助化疗可以提高肿瘤细胞减灭术达到无肉眼残留的几率,缩小手术范围,减少围手术期并发症的发生,但不能提高患者的PFS和OS。新辅助化疗后间歇性肿瘤细胞减灭术中满意缩瘤的标准应为无肉眼残留病灶。患者的FIGO分期和最大原发肿瘤直径可能对晚期卵巢癌患者选择治疗方案提供帮助。     

新辅助化疗PTX和DDP对子宫颈癌患者的疗效分析

目的:评价Ⅰb-Ⅱb期宫颈癌于根治术前给予紫杉醇和顺铂新辅助化疗的疗效及安全性。方法:将130例Ⅰb-Ⅱb期巨块型宫颈癌患者(肿瘤直径>4cm)随机分为新辅助化疗组和对照组。新辅助化疗组术前作2～3周期(紫杉醇和顺铂方案)的静脉化疗,化疗后行宫颈癌根治术,有指征者常规补充化疗或放疗;对照组除不做术前化疗外,手术及术后其他治疗相同。结果:新辅助化疗组临床有效率(CR+PR+MR)95%,新辅助化疗组5a生存率和无瘤生存率分别为85.7%、80%,高于对照组60.0%、50.0%,P<0.01(u=6.668,4.819)。结论:新辅助化疗(紫杉醇和顺铂方案)可提高Ⅰb-Ⅱb期巨块型宫颈癌的手术成功率,延长患者的生存期。     

宫颈癌新辅助化疗临床研究现状

新辅助化疗是指在局部治疗（手术或放疗）前给予的全身化疗。近二十余年来国内外学者对宫颈癌新辅助化疗联合手术或放疗的治疗模式进行了一些探索,取得一定经验。但新辅助化疗在宫颈癌治疗中的地位仍未明确,且对其化疗方案选择目前无统一认识。对新辅助化疗在宫颈癌治疗方面的最新进展、多种新辅助化疗方案应用于宫颈癌的疗效及其发展趋势做综述。     

宫颈癌新辅助化疗的疗效评估

宫颈癌是妇科最常见的恶性肿瘤,严重威胁妇女生命健康,是一个亟待解决的全球公共卫生问题。目前,宫颈癌的治疗以手术和放疗为主,化疗为辅。新辅助化疗（neoadjuvant chemotherapy,NACT）是宫颈癌患者临床常用的辅助治疗方案,具有缩小原发肿瘤体积、减少肿瘤转移等优势。然而,由于个体差异性和肿瘤异质性,不是所有患者都对化疗有应答。同时,NACT还有一定的毒性反应,如脱发、中性粒细胞减少和脏器损伤等,甚至可能导致患者死亡。目前临床最常用血清鳞状细胞癌抗原（squamous cell carcinoma antigen,SCC-Ag）和影像学检查来评估NACT的疗效,但具有一定的局限性。从影像学、病理学、分子标志物、毒性反应和生存情况5个方面综述宫颈癌NACT疗效的评估方法,为NACT的临床评估提供依据,并有助于个体化治疗方案的选择和应用。     

宫颈癌新辅助化疗临床研究现状

新辅助化疗是指在局部治疗（手术或放疗）前给予的全身化疗。近二十余年来国内外学者对宫颈癌新辅助化疗联合手术或放疗 的治疗模式进行了一些探索,取得一定经验。但新辅助化疗在宫颈癌治疗中的地位仍未明确,且对其化疗方案选择目前无统一认识。对新辅助化 疗在宫颈癌治疗方面的最新进展、多种新辅助化疗方案应用于宫颈癌的疗效及其发展趋势做综述。     

预测晚期宫颈癌新辅助化疗疗效的分子标记物研究进展

新辅助化疗（neoadjuvant chemotherapy,NACT）作为综合治疗的一种方法在宫颈癌中主要用于治疗ⅠB2和ⅡA期的巨块型（肿瘤直径≥4 cm）晚期宫颈癌。大部分学者的研究认为,NACT能缩小肿瘤体积,提高可手术率及手术切除率,同时能降低手术并发症,有效率多高达80%以上,其中9%～18%的患者术后病理证实完全缓解。然而还有部分患者对NACT不敏感,如果对这部分患者仍进行NACT治疗就会延误治疗时机造成不必要的痛苦和浪费。近年国内外的研究者做了大量研究试图寻找出与NACT疗效相关的分子标记物,期望能够在分子水平尽早对患者进行NACT疗效预测,发现那些对NACT不敏感的患者而尽早采用其他综合治疗措施,从而改善患者的预后和生存率。综述与宫颈癌NACT疗效相关的分子标记物的研究现状。     

Cisplatin/Etoposide Chemotherapy for Recurrent or Primarily Advanced Cervical Carcinoma

Thirty-eight women with primarily advanced (n= 10) or recurrent (n= 28) cervical carcinoma were treated with cisplatin (30 mg/m²/day intravenously) and etoposide (60 mg/m²/day intravenously) for 3 days followed by oral etoposide, 50 mg daily for 7 days, repeated at 28-day intervals. The response rate was 39% (95% confidence limits 24–55%) with response duration of 5 to 36 months. The main toxicities were neutropenia (21% developing neutropenic fever), alopecia, stomatitis, and nausea and vomiting. Despite this all responders had maintained or improved quality of life as defined by symptoms and performance status.     

Combined Cisplatin and Carboplatin Chemotherapy for Treatment of Advanced Epithelial Ovarian Cancer

Purpose. The primary goal of this trial was to evaluate the clinical activity and the toxicity of a combination of cisplatin and carboplatin for women with advanced-stage epithelial ovarian cancer. Patients and methods. Fifty-one consecutive evaluable patients with untreated stage III and IV epithelial ovarian cancer received 360 mg/m² carboplatin on Day 1 and 50 mg/m² cisplatin on Day 2 administered intravenously every 28 days for six cycles. Drug doses were adjusted for hematologic toxicity based on nadir counts during the prior therapy course. Dose levels included 300-400 mg/m² carboplatin and 50-75 mg/m² cisplatin. Second-look surgery was optional. Endpoints were clinical response, surgical response, progression-free survival, and survival. Results. Of 8 patients with measurable disease, 3 (37.5%) had a clinical compete response, and 3 (37.5%) had a clinical partial response, for an overall clinical response rate of 75%. Of 39 patients who began chemotherapy with abnormal serum levels of CA 125, 31 (79%) achieved normalization of CA 125 at the completion of chemotherapy. Thirteen patients underwent second-look laparotomy. Of these, 7 (54%) had a pathological compete response, and 2 (15%) had a partial response. The median progression-free survival was 14 months, and the overall median survival was 32.5 months. Neutropenia and thrombocytopenia were the main dose-limiting toxicities. In addition, 9 patients developed grade 2 and 3 developed grade 3 ototoxicity. Conclusion. This regimen is very active against advanced-stage epithelial ovarian cancer. The degree of ototoxicity observed is worrisome, but such toxicity may be ameliorated by limiting the dose of cisplatin and increasing the dose of carboplatin.     

The Efficacy and Safety of Neoadjuvant Chemotherapy in Treatment of Locally Advanced Carcinoma Cervix

Objective

A prospective cohort study in a teaching hospital to assess the efficacy and safety of neoadjuvant chemotherapy in the treatment of locally advanced carcinoma cervix.

Method

Neoadjuvant chemotherapy in the form of cisplatin 75 mg/m² and paclitaxel 135 mg/m² on day 1 and repeated at 14 days’ interval for up to a maximum of three courses.

Results

Neoadjuvant chemotherapy in cervical cancer was effective in the downstaging of the disease. Downstaging was observed in 19.23 % of patients after two cycles and in 50 % of patients after three cycle of NACT. Operability increases to 33.3 and 38.4 % after two and three cycles of NACT, respectively. Complete pathological response was observed in 37.5 % of patients after NACT. No significant adverse effect in the feasibility of surgery was observed.

Conclusion

The present study showed that neoadjuvant chemotherapy was an effective and well-tolerated mode of therapy with significantly less morbidity and mortality.     

Chemotherapy Followed by Radiotherapy versus Radiotherapy Alone in Locally Advanced Cervical Cancer: A Randomized Study

Between August 1990 and January 1992, 184 patients with squamous cell carcinoma of the cervix, FIGO stage IIB-IVA, were randomized to receive either two cycles of bleomycin, ifosfamide-mesna, and cis-platinum (BIP) chemotherapy (CT) followed by radiotherapy (RT) ("CT-RT group," n = 94) or RT alone (RT group, n = 90). In the CT-RT group, of 89 evaluable patients, 64 responded: complete response (CR) 4 (4.5%) and partial response 60 (67.5%). Of the remaining 25 patients, 23 had stable disease and 2 progressed. Eighty of 89 patients completed RT as planned. Following RT 56 (70%) achieved CR, 19 (23.7%) had residual disease, and 5 (6.3%) had progressed. CT responders had a better response to RT: 83% (49/59) vs 33.3% (7/21), P < 0.01. The stage of disease, histologic grade, duration of symptoms, and history of smoking had no influence on the response to CT. Patients aged >45 years and those with lib >10 g/dl had significantly better response. Nausea/vomiting, alopecia, grade I-II myelosuppression, diarrhea, and mucositis were the major side effects of CT. Two patients died of CT toxicity. In the RT group, 88 patients were evaluable: 61 (69.3%) patients achieved CR, 25 had residual disease, and 2 progressed. The side effects of RT were cystitis, proctitis, and local skin reaction. These were equally distributed between the two groups. There was no significant difference in overall and disease-free survival in the two groups.     

中晚期宫颈癌的介入治疗及其临床意义

目的探讨中晚期宫颈癌髂内动脉化疗栓塞的疗效及其临床意义.方法43例中晚期宫颈癌(Ⅱb期13例,Ⅲa-b期23例,Ⅳa期7例)行髂内动脉化疗栓塞107次,观察并评定其近期疗效.结果近期有效率为72.1%,其中2例Ⅱb期经2次介入治疗后癌细胞消失,无需治疗,另25例行宫颈癌根治术,断端无癌细胞,淋巴结转移阳性者3例.结论介入性髂内动脉化疗栓塞是治疗中晚期宫颈癌的安全而有效的方法,它能缩小原发病灶,提高手术切除率,具有重要的临床意义.     

Role of Neoadjuvant Chemotherapy (NACT) Followed by Surgical Cytoreduction in Advanced Epithelial Ovarian Cancer

Objectives

To study the role of neoadjuvant chemotherapy (NACT) followed by surgical cytoreduction in the management of advanced epithelial ovarian cancers.

Methods

A prospective hospital based study of patients with advanced epithelial ovarian cancers (stage III and IV) was conducted at Gujarat Cancer & Research Institute, Ahmedabad during August 2008 to August 2010. Total 50 patients were treated with NACT followed by surgical cytoreduction and followed up till August 2010. Response to NACT, optimal cytoreduction rate and overall response rate were analyzed.

Results

There were 43 patients (86%) with stage III disease and 7 (14%) with stage IV disease. All patients were given NACT and after NACT, complete response occurred in 17 patients (34%), 27 (54%) had partial response. Optimal surgical cytoreduction could be achieved in 36(72%) of the patients. The median follow up was 19 months.

Conclusions

NACT followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers.     

新辅助化疗在宫颈癌治疗中的作用

新辅助化疗的概念于1983年首次提出。目前新辅助化疗在宫颈癌治疗方面虽仍有争议,但随着医疗技术的不断发展其作用优势逐步显现。新辅助化疗不但可以缩小肿瘤体积、提高手术切除率,而且可延长妊娠期宫颈癌患者的妊娠时间,使其获得存活新生儿。故新辅助化疗的出现为局部晚期宫颈癌患者、晚期宫颈癌患者和妊娠期宫颈癌患者的治疗提供了新的思路。综述新辅助化疗概念的提出、所存争议、作用机制及其在宫颈癌综合治疗中的作用。     

不同剂量紫杉醇联合顺铂新辅助化疗在宫颈癌的应用

目的:探讨不同剂量紫杉醇联合顺铂新辅助化疗对ⅠB2～ⅡB期宫颈癌的近期疗效及毒副反应.方法:58例宫颈癌患者随机分配为TP1组和TP2组,TP1组紫杉醇用量60mg/m2、TP2组135mg/m2,顺铂均为60mg/m2,采用1～3个疗程化疗,化疗间隔TP1组为10天,TP2组为21天,化疗结束后行宫颈癌根治术,比较其近期疗效及毒副反应.结果:IP1组有效率76.7%(23/30),TP2组82.1%(23/28),两组疗效相近,P＞0.05;白细胞减少TP2组(32.1%,9/28)多于TP1组(10.0%,3/30),P＜0.05;余毒副反应差异无显著性,P＞0.05.结论:小剂量紫杉醇60mg/m2联合顺铂60mg/m2化疗方案在宫颈癌新辅助化疗中值得推荐.