Preliminary results of neoadjuvant chemotherapy with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who are inadequate for optimum primary surgery

AIM: This study was performed to evaluate the efficacy of neoadjuvant chemotherapy (NAC) with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who were inadequate for primary optimal surgery. METHODS: Patients with histologically confirmed epithelial ovarian cancer at International Federation of Gynecology and Obstetrics stages IIIc/IV that was unresectable according to computed tomography findings were eligible for this study. Three cycles of paclitaxel plus cisplatin NAC were administered and the response was evaluated. Patients were then selected for interval debulking surgery or three cycles of additional chemotherapy with the same regimen according to the resectability and response. Interval debulking surgery followed by second-line chemotherapy was applied to patients with no response to NAC. During the same period, patients who did not agree to the protocol were treated by the conventional method of tumor debulking surgery followed by adjuvant chemotherapy, and served as the control group. A comparison of both groups of patients was carried out. RESULTS: A total of 40 patients were involved in the study. All patients were evaluable. Eighteen patients underwent NAC and 22 patients were treated by conventional therapy. Optimal debulking was possible in 14 patients (77.8%) in the NAC group and in 10 patients (45.5%) in the conventional therapy group (P = 0.04). The mean estimated blood loss was 620 cc (range: 300-1500 cc) in the NAC group and 1061 cc (range: 300-3500 cc) in the conventional therapy group (P = 0.04). However, no significant differences were found in the disease-free and overall survival rates between the two groups (P = 0.48 and P = 0.61, respectively). CONCLUSION: NAC provided a higher rate of optimum cytoreduction and equivalent survival with less invasive surgery and reduced morbidity compared with conventional therapy in patients with advanced epithelial ovarian cancer inadequate for primary optimum surgery. Therefore, NAC may be a valuable alternative treatment for these patients.     

Neoadjuvant chemotherapy and cytoreductive surgery in epithelial ovarian cancer

Ovarian cancer is one of the leading causes of death among gynecological cancers. This is because the majority of patients present with advanced stage disease. Primary debulking surgery (PDS) followed by adjuvant chemotherapy is still a mainstay of treatment. An optimal surgery, which is currently defined by leaving no gross residual tumor, is the goal of PDS. The extent of disease as well as the operative setting, including the surgeon’s skill, influences the likelihood of successful debulking. With extensive disease and a poor chance of optimal surgery or high morbidity anticipated, neoadjuvant chemotherapy (NACT) prior to primary surgery is an option. Secondary surgery after induction chemotherapy is termed interval debulking surgery (IDS). Delayed PDS or IDS is offered to patients who show some clinical response and are without progressive disease. NACT or IDS has become more established in clinical practice and there are numerous publications regarding its advantages and disadvantages. However, data on survival are limited and inconsistent. Only one large randomized trial could demonstrate that NACT was not inferior to PDS while the few randomized trials on IDS had inconsistent results. Without a definite benefit of NACT prior to surgery over PDS, one must carefully weigh the chances of safe and successful PDS against the morbidity and risks of suboptimal surgery. Appropriate selection of a patient to undergo PDS followed by chemotherapy or, preferably, to have NACT prior to surgery is very important. Some clinical characteristics from physical examination, serum tumor markers and/or findings from imaging studies may be predictive of resectability. However, no specific features have been consistently identified in the literature. This article will address the clinical data on prediction of surgical outcomes, the role of NACT, and the role of IDS.     

Histopathology predicts clinical outcome in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and debulking surgery

Objective

To analyze the factors prognostic of survival in patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery.

Methods

Outcomes were retrospectively in patients with advanced EOC or peritoneal cancer who received neoadjuvant paclitaxel and carboplatin chemotherapy every 3 weeks for three to four cycles, followed by interval debulking surgery and three additional cycles of the same regimens from January 2001 to November 2010. Therapeutic response was assessed histopathologically as grade 0 to 3, based on the degree of disappearance of cancer cells, displacement by necrotic and fibrotic tissue, and tumor-induced inflammation. Factors prognostic of progression-free survival (PFS) and overall survival (OS) were calculated.

Results

The 124 enrolled patients had a median age of 62 years (range, 35–79 years). Viable cancer cells were observed in specimens resected from 72 patients (58%) at interval debulking surgery after NAC. Multivariate analysis using the Cox proportional hazard model showed that advanced (stage IV) disease (hazard ratio [HR] = 1.94, p = 0.003), residual cancer at the end of surgery ≥ 1 cm (HR = 3.78, p < 0.001), and histological grade 0–1 (HR = 1.65, p = 0.03) were independent predictors of decreased OS. Grade 0–1 was also an independent predictor of increased risk of relapse within 6 months (odds ratio = 8.42, p = 0.003).

Conclusions

Residual disease of ≥ 1 cm, advanced stage, and the presence of more viable disease in resected specimens are prognostic factors for survival in advanced EOC patients receiving NAC followed by interval debulking surgery.     

Optimizing the treatment of ovarian cancer: Neoadjuvant chemotherapy and interval debulking versus primary debulking surgery for epithelial ovarian cancers likely to have suboptimal resection

Objective

To: a) identify prognostic factors in patients with epithelial ovarian cancer treated with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS), and b) compare post-surgical survival between patients treated with NACT/IDS for presumed unresectable disease and stage IIIC/IV patients who underwent suboptimal primary debulking surgery (PDS).

新辅助化疗在晚期卵巢上皮性癌综合治疗中的临床研究

目的探讨新辅助化疗(NACT)在晚期卵巢上皮性癌(卵巢癌)治疗中的临床意义。方法回顾性分析四川省肿瘤医院1999年1月至2008年12月收治的晚期卵巢癌(FIGOⅢ、Ⅳ期)患者161例,其中73例接受新辅助化疗+手术治疗+化疗(研究组),88例行初次肿瘤细胞减灭术+化疗(传统组)。结果研究组肿瘤手术切除率(即理想减瘤率)77.1%,传统组为56.8%,差异有统计学意义(P=0.012)。研究组术中失血量、术中输血量、术中补液量、腹水量和手术时间与传统组比较,差异均有统计学意义(P<0.05)。研究组平均无进展生存期(PFS)和总体生存期(OS)分别为22.7(7～63.5)个月和33.5(13.8～92.3)个月,传统组分别为21.7(4.3～61.2)个月和32.1(12.4～114.9)个月,两组比较差异无统计学意义(分别为P=0.082和P=0.293)。研究组和传统组5年生存率分别为17.8%和11.4%,差异无统计学意义(P=0.503)。结论行新辅助化疗+手术治疗+化疗治疗晚期卵巢上皮性癌的PFS、OS与仅行初次肿瘤细胞减灭术+化疗相似,但前者能明显提高肿瘤的手术切除率、减少术中出血量,同时并没有增加手术的并发症。     

Neoadjuvant chemotherapy or primary surgery in advanced epithelial ovarian carcinoma

Abstract. Kayikçiōlu F, Köse MF, Boran N, Çalişkan E, Tulunay G. Neoadjuvant chemotherapy or primary surgery in advanced epithelial ovarian carcinoma.
Neoadjuvant chemotherapy has been proposed as an alternative approach to conventional surgery as initial management of bulky ovarian cancer, with the goal of performing adequate debulking in the interval surgery. Two hundred five consecutive patients with advanced ovarian cancer were divided into two groups. Neoadjuvant chemotherapy followed by interval surgery was performed in 45 of 205 patients. The remaining 158 patients received primary surgery plus adjuvant chemotherapy. Optimal cytoreductive surgery rates were significantly higher in the neoadjuvant CT group ( P< 0.001). In multivariate analysis, only residual tumor diameter and appendix involvement were found to affect total survival significantly in both groups. Five-year survival and median survival were not statistically different when all patients treated conventionally were compared with all patients treated with neoadjuvant chemotherapy. Primary chemotherapy followed by interval debulking surgery in a selected group of patients does not appear to worsen prognosis, but it permits less aggressive surgery and improves patients' quality of life.     

Remaining controversies in the upfront management of advanced ovarian cancer

Ovarian cancer (OC) is one of the leading causes of cancer-related death in women. In the last decades, a lot of energy and resources have been put into a number of clinical trials, with some success. Nevertheless, the prognosis of patients diagnosed with advanced disease remains extremely poor. As research moved forward, some crucial questions with regard to the optimal upfront management of patients with advanced OC (AOC) have remained unanswered. In this article, we review the rationale behind these controversial issues, and provide the levels of evidence supporting the current recommendations for AOC management.     

Neoadjuvant chemotherapy in advanced ovarian cancer: a case-control study

The aim of this study was to compare the outcome of patients with advanced ovarian carcinoma treated with neoadjuvant chemotherapy (NACT) with those treated conventionally with primary debulking surgery. From 1994 to 2003, all consecutive cases of advanced-stage epithelial ovarian carcinoma treated with NACT at the University of Bari were identified. A well-balanced group of women who underwent primary debulking surgery followed by platinum-based chemotherapy was selected as controls. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival. Thirty women with advanced-stage epithelial ovarian carcinoma were treated with NACT and compared to 30 patients who underwent primary debulking surgery. Patients in the NACT were significantly older and had a poorer performance status compared to the controls. However, no statistical difference was observed in overall disease-specific survival (P= 0.66) and disease-free survival (P= 0.25) between the two groups. Although patients in the NACT group are significantly older and have a poorer performance status, this treatment modality does not compromise survival. Prospective randomized trials comparing NACT to conventional treatment to determine the quality of life and cost/benefit outcomes are now appropriate for women presenting advanced epithelial ovarian cancer.     

Safety and efficacy of neoadjuvant chemotherapy with bevacizumab in advanced-stage peritoneal/ovarian cancer patients

Objective

The aim of this study was to evaluate the outcomes of neoadjuvant chemotherapy (NAC) with bevacizumab (Bev) at our institute.

上皮性卵巢癌的一线化疗

化疗是上皮性卵巢癌主要的辅助治疗手段,铂类为基础的联合化疗是上皮性卵巢癌的一线化疗方案,但在药物组成、剂量强度、给药方式、腹腔化疗、新辅助化疗及维持和巩固治疗方面仍值得进一步探索。     

晚期上皮性卵巢癌患者“间歇性肿瘤细胞减灭术”手术适应证的探讨

目的:探讨间歇性肿瘤细胞减灭术(IDS)的适应证。方法:采用回顾性病例对照研究,分析2000年1月至2009年12月间71例初次肿瘤细胞减灭术不满意的ⅢC～Ⅳ期卵巢上皮癌(包括原发性腹膜癌,原发性输卵管癌)患者的资料。A组(n=41)初次减灭术后单纯化疗6～8疗程;B组(n=30)经3～4个疗程化疗后行间歇性肿瘤细胞减灭术,然后继续化疗4～6疗程。化疗方案均为铂类为基础的联合化疗。两组患者的化疗方案和疗程无差异。通过比较两组患者的临床特征、手术及生存情况,以及B组患者IDS术前CA125、B超检查与术后病理结果的对应关系,总结IDS的适应证。结果:B组30例患者中23例(76.7%)最终达到满意减瘤,共有11例术后病理结果为阴性,术前CA125或B超对病理结果阳性预测的敏感度差,CA125的特异性达100%。CA125联合B超的预测准确率为70%。A、B组的五年生存率(P=0.790)、OS(P=0.254)和PFS(P=0.289)均无显著性差异。B组中无肉眼残留病灶患者的PFS和OS较A组有明显延长的趋势。结论:间歇性肿瘤细胞减灭术主要适应证是:初次肿瘤细胞减灭术采用"基本术式",3个疗程化疗后部分缓解,CA125仍异常;或CA125恢复正常,最好经PET-CT或增强CT明确有残留病灶。残留病灶有可能通过再次手术切除干净,达到无肉眼残留,这部分患者有可能生存获益。     

A retrospective analysis of neoadjuvant platinum-based chemotherapy versus up-front surgery in advanced ovarian cancer

Abstract.   Steed H, Oza AM, Murphy J, Laframboise S, Lockwood G, De Petrillo D, Sturgeon J, Rosen B. A retrospective analysis of neoadjuvant platinum-based chemotherapy versus up-front surgery in advanced ovarian cancer. Int J Gynecol Cancer 2006; 16(Suppl. 1): 47–53.
The objective of this study is to compare progression-free survival (PFS) and overall survival (OS) of ovarian cancer patients treated with neoadjuvant chemotherapy and surgery to primary surgery and postoperative chemotherapy. Retrospective analysis from 1998 to 2003 of 116 patients with ovarian cancer was performed. Fifty women diagnosed by positive cytology received three cycles of carboplatin and paclitaxel. Thirty-six patients subsequently underwent cytoreductive surgery and completed three further cycles postoperatively. The OS and PFS were compared in 66 women treated with primary surgery and postoperative chemotherapy. A statistically significant difference was observed for OS ( P = 0.03, HR = 1.85, CI = 1.06–3.23) and PFS ( P = 0.04, HR = 1.61, CI = 1.03–2.53) favoring the primary surgery group. Due to the small numbers, age, grade, stage, pleural effusions, and histologic cell type were controlled for separately in the bivariate analyses. Controlling for stage made the results weaker. A matched subgroup survival analysis was performed on patients who had surgery following neoadjuvant chemotherapy. After matching for stage and grade and controlling age and pleural effusions ( N = 28 matched pairs), there was no statistical difference for OS ( P = 0.95, HR = 1.04, CI = 0.33–3.30) or PFS ( P = 0.79, HR = 1.11, CI = 0.98–1.04). It is concluded that primary surgery should be considered in all patients. Neoadjuvant chemotherapy may be an alternative in a subset of women with the intent to also perform interval debulking.     

Prognostic significance of tumor necrosis in ovarian cancer patients treated with neoadjuvant chemotherapy and interval surgical debulking

The objective of this study was to study the significance of tumor necrosis documented at the time of interval surgical debulking after neoadjuvant chemotherapy. Retrospective chart reviews were carried out from 1997 to 2005 to identify ovarian cancer patients treated with neoadjuvant chemotherapy. Patients' demographics together with disease characteristics, treatment-related variables, and outcomes were recorded. Cox proportional hazard models were built to model time to progression using predictor variables such as age, cancer stage, tumor grade, residual disease, percentage change in CA125 level from baseline, and degree of necrosis in resected tumor specimens. One hundred one patients were included in the study. Optimal debulking was achieved in 74% of the patients. Cox regressions revealed three significant predictive variables of time to first progression: younger age (hazard ratio [HR] = 0.95, 95% CI 0.92-0.98, P= 0.004), residual disease (P= 0.048), and the absence/minimal tumor necrosis after three cycles of neoadjuvant chemotherapy (HR = 1.97, 95% CI 1.01-3.87, P= 0.048). The estimated median survival was 50.66 months (95% CI 46.12-55.20). The lack of or minimal tumor necrosis after neoadjuvant chemotherapy is an independent risk factor for recurrent disease.     

Impact of the time interval from completion of neoadjuvant chemotherapy to initiation of postoperative adjuvant chemotherapy on the survival of patients with advanced ovarian cancer

Objective

To investigate the relationship of the time interval from the completion of neoadjuvant chemotherapy (NAC) to the initiation of postoperative adjuvant chemotherapy (POAC) with the survival outcomes in patients with ovarian cancer.