Neoadjuvant chemotherapy for advanced ovarian cancer

Neoadjuvant chemotherapy with cisplatin or carboplatin was administered to 29 patients with advanced ovarian carcinoma prior to their undergoing definitive cytoreductive surgery. Twenty-eight patients had ascites, eight had pleural effusion, and 16 had extensive upper abdominal disease on computerized tomography scan. The CA125 response to neoadjuvant chemotherapy was highly predictive of survival ( P <0.0005). A 2-log decrease in CA125 prior to surgery resulted in a median survival of 37 months, while patients with less than a 1-log response in CA125 had a survival of 18 months. Bowel resection after neoadjuvant chemotherapy did not benefit patients, as their survival (17 months) was identical to that of patients who were nonresectable and did not undergo any cytoreductive surgery.
Neoadjuvant chemotherapy offers patients with suboptimal ovarian cancer the same survival as primary cytoreductive surgery with interval debulking, yet with only one operative procedure.     

Neoadjuvant chemotherapy in ovarian cancer

Patients with advanced ovarian cancer have a chance of less than 50% after radical debulking surgery. In spite of the currently more effective combination chemotherapy agents that have become available as adjuvant therapy in the last decade, the prognosis of patients with residual tumor mass larger than 1 cm in diameter following surgery is still poor. Neoadjuvant or primary chemotherapy has been suggested as an alternative approach to primary laparotomy of the bulky ovarian cancer. The advantages and available data on neoadjuvant chemotherapy are discussed in this review.     

卵巢癌新辅助化疗相关问题

卵巢癌的标准治疗方案是以手术为主,术后辅以化疗。能否实现理想的肿瘤细胞减灭术将直接影响患者的预后。而大多数晚期卵巢癌患者的初次肿瘤细胞减灭术难以达到满意。新辅助化疗可以改善晚期卵巢癌患者的术前状态,缩小癌灶,缓解病情,为手术的实施和理想肿瘤细胞减灭术的完成创造有利条件。     

Neoadjuvant chemotherapy and surgical considerations in ovarian cancer

PURPOSE OF REVIEW: Despite advances in surgery, it is still not possible in most patients with advanced ovarian carcinoma to remove the tumour completely. For these patients the concept of primary chemotherapy followed by interval debulking has emerged. Various studies in the past few years have evaluated the feasibility and benefit of this therapeutic approach. The available data is presented and discussed in this review. RECENT FINDINGS: The indication for interval surgery was generally based on the response to chemotherapy. However, different criteria of remission were adhered to, possibly explaining the varying outcomes of the trials. The right selection of patients suitable for this approach is crucial and needs further investigation. In these cases with an unfavourable prognosis, higher tumour resection rates and longer median survival times can be achieved by the use of neoadjuvant chemotherapy. SUMMARY: Until the results of a prospective randomized study become available, the use of neoadjuvant chemotherapy followed by debulking laparotomy must still be regarded as experimental, and must not be applied outside clinical trials.     

Neoadjuvant chemotherapy and interval debulking for advanced epithelial ovarian cancer

A retrospective matched-control study was conducted to review our experience with FIGO stage III and IV epithelial ovarian cancer in patients referred after initial laparotomy and biopsy only. The study group comprised 22 patients; planned treatment was two to four cycles of chemotherapy, interval debulking surgery, six more chemotherapy cycles, and second-look laparotomy. Two control groups were matched with the study group according to FIGO stage, histologic type, and grade (2 or 3) and patient age +/- 5 years. The first control group (22 patients) had greater than 2 cm residual disease after initial surgery; their planned treatment was a minimum of six cycles of chemotherapy plus second-look laparotomy. The second control group (18 patients) was referred after initial laparotomy and biopsy only; their disease was immediately reexplored and debulked. Subsequent planned treatment was a minimum of six cycles of chemotherapy plus second-look laparotomy. All patients received cisplatin-based chemotherapy. Optimal cytoreduction to less than or equal to 2 cm was achieved for 77% of the study group vs 39% of the immediate-reexploration group (P = 0.02). Median survival times for the three groups were not different (16 vs 19.3 vs 18 months, respectively) (P = 0.58). Within the study group, patients who were optimally debulked survived significantly longer than those who were not (18.1 vs 7.5 months) (P = 0.02). Morbidity of the interval debulking procedure was acceptable. Study findings suggest that patients with bulky residual disease have a uniformly poor prognosis regardless of the timing of further surgery.     

Neoadjuvant chemotherapy in the Medicare cohort with advanced ovarian cancer

Objective

The value of neoadjuvant chemotherapy (NAC) for the treatment of advanced ovarian cancer has yet to be determined. While NAC may facilitate and simplify complete cytoreduction and reduce the risk of surgery, the delay of surgery related to NAC needs to be balanced against any potential benefit.

Methods

Surveillance, Epidemiology and End-Results (SEER) data linked to Medicare claims were used to identify 6844 women with treated stage III/IV epithelial ovarian cancer (1995-2005). Patients were classified by primary treatment (surgery (PDS) or chemotherapy), and the primary chemotherapy group was characterized as having NAC or palliative chemotherapy (PC) based on whether there was documentation that surgery was recommended. We compared surgical complications and survival between the groups.

Results

4827 (71%) of women were treated with PDS, 958 received NAC (14%) and 1059 (15%) had PC. Only 577 (60%) of women with NAC underwent surgery and they had fewer ostomies (8.5% vs. 19.2%, p < 0.001) and fewer infections, gastrointestinal and pulmonary complications than PDS (all p < 0.01). Comparing NAC to PDS there was a 16% increase in the risk of death at 2 years (RR 1.16, 95%CI 1.01-1.34) for women with stage III disease and a 15% reduction in the risk for women with stage IV disease (RR 0.85, 95%CI 0.73-0.99).

Conclusions

NAC followed by surgery was associated with fewer surgical complications than PDS. The direction and magnitude of the difference in survival between women receiving NAC and those receiving PDS differed according to the stage of disease and follow up time.     

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.     

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.     

Neoadjuvant chemotherapy for advanced ovarian cancer: the role of cytology in pretreatment diagnosis

OBJECTIVE: The objective was to determine the role of cytology in the pretreatment evaluation of women with clinical findings consistent with ovarian cancer who are being considered for neoadjuvant chemotherapy. METHODS: Pretreatment cytology slides were available for review from 60 of 72 consecutive patients treated with platinum-based neoadjuvant chemotherapy who were believed to have ovarian cancer based on clinical findings. Fifty of the 72 patients had evidence of both intraabdominal and extraabdominal tumor spread prior to treatment. Fifty-three of 66 patients had CA125 values >500 U/mL, 34 being >1500 U/mL. Pretreatment cytology was compared to surgical specimens obtained following chemotherapy. RESULTS: Cytologic findings were consistent with ovarian cancer in 55 patients, not consistent with ovarian cancer in 4 cases, and insufficient for diagnosis in one case. Forty-seven of the 60 patients underwent surgery. Forty-two of 43 patients with cytology consistent with ovarian cancer had epithelial ovarian cancers at surgery. One had no pathologic evidence of disease. Three of the 4 patients thought not to have cytology consistent with ovarian cancer underwent surgery following neoadjuvant chemotherapy. Two had ovarian epithelial cancers and one had a mesonephric adenocarcinoma. The one patient with cytology insufficient for diagnosis also had an epithelial ovarian cancer at diagnosis. CONCLUSIONS: Cytology proved to be extremely helpful in supporting the clinical impression of an apparent advanced ovarian cancer. When the cytologic diagnosis does not match the clinical impression, communication between the cytologist or pathologist and the clinician is essential.     

Neoadjuvant chemotherapy in stage X ovarian carcinoma

Seventeen patients with presumed advanced ovarian cancer were treated initially with platinum-based chemotherapy. All patients had either cytologic or histologic findings consistent with an ovarian adenocarcinoma. Eight patients subsequently had surgery: one patient had a complete pathological response and one patient had microscopic disease; both are alive without evidence of disease. Five patients were surgically debulked to less than 1 cm, and one patient had large residual disease after surgery. Four of these patients are alive with disease and one died of disease. Nine patients did not have surgery; two patients had no response to chemotherapy and four patients had stabilization of disease. These six patients have died. Two patients had initial partial responses and are alive with disease. One patient with a complete clinical response at autopsy was without evidence of disease. The follow-up ranged from 7 to 109 months; the median survival was 15 months. Comparison of these 17 patients with 21 patients with stage IV disease and 38 suboptimally debulked patients with stage III disease treated during the same period with aggressive surgery followed by chemotherapy revealed no statistical difference in overall survival between these 17 patients and the two groups of patients. The postoperative hospital stay and complication rate were significantly lower for the 9 patients who had surgery than for the 21 patients with stage IV disease. This report suggests that in patients with presumed ovarian cancer and significant medical problems or with a priori nondebulkable tumor, initial chemotherapy and then surgery should be considered.     

Advanced ovarian cancer: Neoadjuvant chemotherapy plus surgery and HIPEC as up-front treatment

Epithelial ovarian cancer (EOC) is one of the most common malignancies and one of the principal causes of death in gynecological neoplasms. The majority of EOC patients present with an advanced International Federation of Gynecology and Obstetrics stage disease. The current standard treatment for these patients consists of complete cytoreduction and combined systemic chemotherapy of a platinum agent and paclitaxel. Even if the majority of patients with EOC respond to first-line platinum based chemotherapy, almost 20% of them are resistant or refractory. According to these data, the main risk is for a certain number of patients to have undergone cytoreductive surgery (CRS) and subsequent hyperthermic intraoperative peritoneal chemotherapy (HIPEC) in a useful way. Radical surgery, especially in advanced cases, is associated with a high incidence of postoperative morbidity and mortality, which could be increased by the HIPEC. Every effort should be made for previously selected patients to improve outcome and optimize resources. Over the last decade, new options have been introduced to prolong survival. Improved long-term results can be achieved using CRS in combination with intraoperative HIPEC. This combination has also been used in an up-front setting. Controversial outcomes have been reported for neoadjuvant platinum-based chemotherapy. Different papers have been published reporting discordant results. Further studies are needed.     

Neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy in patients with primarily unresectable,advanced-stage ovarian cancer

OBJECTIVE: The aim of this review is to report our experience and the feasibility of neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer. METHODS: Forty-five patients with primarily unresectable advanced-stage epithelial ovarian cancer were treated in our center between 1995 and 2002 by platinum-based neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. Their files were reviewed retrospectively. RESULTS: At the end of neoadjuvant chemotherapy, according to RECIST criteria, 1 patient (2.2%) had achieved a clinical complete response (CR), 33 (73.4%) a partial response (PR), and 8 (17.8%) had stable disease (SD). Only 3 (6.6%) patients showed disease progression (PD). Surgery was performed in patients with objective response or SD after a median number of 4 courses (range: 2-6) of induction chemotherapy. A complete macroscopic debulking was achieved in 24 (53.3%) out of 39 patients in whom cytoreductive surgery was performed. For the entire group, median overall survival was 29 months. Survival was significantly improved in patients with optimal debulking compared to patients with persistent tumor after surgery: 41 months versus 23 months (P = 0.0062). Median survival for patients responding to neoadjuvant chemotherapy (CR and PR) was 44 months compared to 27 months for patients with SD or PD after initial chemotherapy (P = 0.01). Neither treatment-related deaths nor significant toxicities were observed. CONCLUSION: Neoadjuvant chemotherapy followed by optimal debulking may be a safe and valuable treatment alternative in patients with primarily unresectable advanced-stage bulky ovarian cancer. Patients with an objective response to chemotherapy or absence of macroscopic residual tumor after surgery have a better outcome. This approach is currently being tested in large, prospective randomized clinical trials.     

卵巢癌的腹腔化疗

卵巢癌是常见的妇科恶性肿瘤之一,病死率居女性生殖系统恶性肿瘤之首.目前常规的治疗方案是最大限度的细胞减灭术并辅以铂类为主的化疗.因此,化疗是卵巢癌综合治疗的重要手段之一.由于腹腔内直接播散或种植是卵巢癌最常见的转移方式,因而,直接将化疗药物灌注到卵巢癌患者腹腔内,使肿瘤部位药物浓度提高,增强对肿瘤细胞杀伤能力的腹腔化疗(IP)逐渐受到重视.     

晚期卵巢癌新辅助化疗的Meta分析

目的:评价新辅助化疗对晚期卵巢癌患者总生存期及无进展生存期的影响,探讨新辅助化疗在晚期卵巢癌的应用价值。方法:计算机检索PubMed数据库、Med-line数据库、EMbas数据库、Cochrane Library数据库、万方数据库、中国学术文献总库(CNKI)、中国生物医学文献数据库(CBM),手工检索《中华妇产科杂志》,《中国实用妇科与产科杂志》,《实用妇产科杂志》,《生殖与避孕》,《现代妇产科进展》5本妇产科杂志。语言种类为中文和英文,网上检索时间不限。试验组行新辅助化疗,即以铂类为基础的化疗后行细胞减灭术;对照组行传统治疗,即细胞减灭术后行规范性化疗。结果:共纳入3篇文献,提取数据后,Review Manager5.0软件进行Meta分析,两组的总生存期合并后的RR值为0.96(95%CI,0.90～1.03),两组的无进展生存期合并后的RR值为1.00(95%Cl 0.93～1.09),森林图菱形均与垂直线相交。结论:新辅助化疗并未改善晚期卵巢癌患者的预后。