Clinical outcome of neoadjuvant chemotherapy for advanced ovarian cancer

Objective

To evaluate clinical outcome in patients selected to receive neoadjuvant chemotherapy (NACT) compared to primary debulking surgery (PDS).

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).

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.

The impacts of neoadjuvant chemotherapy and of debulking surgery on survival from advanced ovarian cancer

Objectives

Women with advanced ovarian cancer are treated with chemotherapy either before (neoadjuvant) or after surgery (primary debulking). The goal is to leave no residual disease post-surgery; for women treated with primary debulking surgery this has been associated with an improvement in survival. It has not been shown that the survival advantage conferred by having no residual disease post-surgery is present for women who receive neoadjuvant chemotherapy.

Methods

We reviewed the records of 326 women with stage IIIc or IV serous ovarian cancer. We determined if they received neoadjuvant chemotherapy or primary debulking surgery and we measured the extent of residual disease post-surgery. We estimated seven-year survival rates for women after various treatments.

Results

Women who had neoadjuvant chemotherapy were more likely to have no residual disease than women who had primary debulking surgery (50.1% versus 41.5%; p = 0.03) but they experienced inferior seven-year survival (8.6% versus 41%; p < 0.0001). Among women who had primary debulking surgery, those with no residual disease had much better seven-year survival than women who had any residual disease (73.6% versus 21.0%; p < 0.0001). Women who had no residual disease after debulking surgery and who received intraperitoneal chemotherapy had a seven-year survival of 90%.

Conclusions

Neoadjuvant chemotherapy should be reserved for ovarian cancer patients who are not candidates for primary debulking surgery. Among women with no residual disease after primary debulking surgery, intraperitoneal chemotherapy extends survival.     

Improved optimal cytoreduction rates for stages IIIC and IV epithelial ovarian, fallopian tube, and primary peritoneal cancer: a change in surgical approach

OBJECTIVE: To determine the impact of the incorporation of extensive upper abdominal debulking procedures on the rates of optimal primary cytoreduction and complications in stages IIIC and IV epithelial ovarian, fallopian tube, and primary peritoneal carcinomas. METHODS: Two groups of patients were identified for comparison. Group 1, the control group, consisted of 70 consecutive patients who underwent "standard" primary cytoreductive surgery before May 2000. Group 2, the study group, was composed of 70 consecutive patients who underwent surgery after January 2001, during which time, a more comprehensive debulking of upper abdominal disease was used, including diaphragm stripping/resection, splenectomy, distal pancreatectomy, liver resection, resection of porta hepatis tumor, and cholecystectomy. RESULTS: The median age of the entire cohort was 60 years (range, 36-88 years). The majority had stage IIIC disease (86%) and serous histology (76%). Optimal cytoreduction (residual disease 相似文献   

Cost effectiveness of neoadjuvant chemotherapy followed by interval cytoreductive surgery versus primary cytoreductive surgery for patients with advanced stage ovarian cancer during the initial treatment phase

Objective

Advanced stage epithelial ovarian cancer (AEOC) can be treated with either neoadjuvant chemotherapy (NACT) or primary cytoreductive surgery (PCS). Although randomized controlled trials show that NACT is non-inferior in overall survival compared to PCS, there may be improvement in short-term morbidity. We sought to investigate the cost-effectiveness of NACT relative to PCS for AEOC from the US Medicare perspective.

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.

Factors associated with delivery of neoadjuvant chemotherapy in women with advanced stage ovarian cancer

Purpose

To identify clinical and non-clinical factors associated with utilization of primary cytoreductive surgery (PCS) or neoadjuvant chemotherapy (NACT) in women with advanced stage epithelial ovarian cancer (EOC).

The lack of significance of Ca125 response in epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and delayed primary surgical debulking

OBJECTIVES: To examine the prognostic significance of Ca125 response to neoadjuvant chemotherapy and delayed primary surgical debulking in epithelial ovarian cancer patients. METHODS: Retrospective chart reviews were carried out from 1997 to 2005 to identify ovarian cancer patients treated with neoadjuvant chemotherapy. Ca125 response was defined as being a decrease of at least 50% from baseline assessment. Ca125 response was assessed in two phases: prior to surgical debulking to reflect the response to neoadjuvant chemotherapy and at the end of primary chemotherapy to assess the response to debulking surgery and further chemotherapy. Cox proportional hazard models were built to model progression-free intervals using predictor variables of: age, cancer stage, tumour grade, residual disease, and Ca125 response. RESULTS: Ninety-one patients were included. About 83% had a positive Ca125 response following three cycles of neoadjuvant chemotherapy preoperatively. Cox regressions revealed two significant predictive variables of prolonged time to first progression: younger age (p=0.002) and microscopic residual disease compared to suboptimal residual disease (p=0.003). Ca125 response to neoadjuvant chemotherapy was not significantly predictive of progression-free survivals. The estimated median survival was 71.42 months (95% CI: 44.34-78.50) in patients with >50% Ca125 decrease from surgery and further chemotherapy whereas in those with no response, the corresponding survival estimate was 44.02 months (95% CI: 33.26-54.79). CONCLUSION: The lack of Ca125 response from neoadjuvant chemotherapy is not an independent prognostic factor. All patients treated with neoadjuvant chemotherapy should undergo radical debulking surgery.     

Patterns of recurrence in advanced epithelial ovarian, fallopian tube and peritoneal cancers treated with intraperitoneal chemotherapy

Objectives

To examine the distribution and outcomes of recurrent disease in patients with ovarian, fallopian tube and peritoneal cancers after optimal cytoreduction and adjuvant intraperitoneal (IP) chemotherapy.

Methods

All patients diagnosed with ovarian, fallopian tube, or peritoneal cancer between 2004 and 2009 who underwent optimal cytoreductive surgery and received adjuvant intravenous (IV) and IP chemotherapy with paclitaxel and a platinum-based agent were eligible. Age, performance status, tumor origin, stage, and grade were recorded. First recurrences were identified using CA125 values, radiographic studies, operative notes, and pathology reports. Sites of recurrence were classified as intraperitoneal (IP), extraperitoneal (EP) or distant. Kaplan-Meier estimates and Cox multivariate regression models were used to assess the associations between recurrent disease distribution and progression-free survival (PFS) and overall survival (OS).

Results

One hundred forty-three patients met the criteria for inclusion. The majority were Stage III (86%) and serous histology (77%). Eighty-four (58.7%) received IV/IP paclitaxel/cisplatin per GOG-172 and 59 (41.3%) received IV/IP paclitaxel/carboplatin. Seventy-two percent completed 6 cycles. Ninety (62.9%) patients manifested a recurrence. One-hundred twelve sites of recurrence were identified with 70 (62.5%) IP and 42 (37.5%) EP and distant sites. Nineteen (21%) recurred in more than one site, i.e. both IP and EP locations. Site of recurrence did not impact OS, however, patients who recurred in multiples sites had significantly worse OS (p < 0.001).

Conclusion

Approximately 40% of patients treated with IP chemotherapy have a first recurrence outside the peritoneal cavity. Though site of recurrence did not affect OS those with multi-focal recurrence demonstrate worse survival.     

Histological response is not a prognostic factor after neoadjuvant chemotherapy in advanced-stage ovarian cancer with no residual disease

Objective

The aim of this study was to evaluate the prognostic impact of the histological response at the time of interval debulking surgery (IDS) in patients treated with neoadjuvant chemotherapy (NACT) for unresectable advanced-stage ovarian cancer (ASOC).

Study design

A retrospective study to select cases fulfilling 4 inclusion criteria: (1) patients with unresectable ASOC; (2) at least 3 courses of platinum and paclitaxel NACT; (3) patients who underwent IDS after NACT and who were free of macroscopic residual disease at the end of debulking surgery and (4) histologic analysis of specimens performed in the same institution. Patients were classified into 3 groups according to the histological response to NACT group 1: no histologic residual disease; group 2: persistent residual disease but with marked histological changes and group 3: persistence of at least 1 site with no changes in the tumour. Survival was compared.

Results

Fifty-eight patients (49 stage IIIC and 9 stage IV) fulfilled inclusion criteria. Respectively 8, 14 and 36 patients were in groups 1, 2 and 3. The median duration of follow-up was 41 months. Three-year event-free survival in groups 1, 2 and 3 was respectively: 63%, 12% and 19% (p = .02).

Conclusions

These results suggest that the degree of the histological response has a limited impact on survival when complete debulking surgery is achieved at IDS. The degree of tumour cell viability after initial chemotherapy is not a reliable marker for modifying chemotherapy after debulking surgery in such patients.     

A phase II clinical trial of pegylated liposomal doxorubicin and carboplatin plus bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer

Objective

To assess the safety and efficacy of pegylated liposomal doxorubicin (PLD), carboplatin, plus bevacizumab in patients with ovarian, fallopian tube, or primary peritoneal cancer.

Methods

Patients with platinum-sensitive, recurrent disease received PLD 30 mg/m² and carboplatin area under the curve (AUC) 5 on Day 1 plus bevacizumab 10 mg/kg on Days 1 and 15 of every 28-day cycle, for a maximum of 10 cycles. The primary endpoint was objective response rate (ORR) [complete + partial response]; additional endpoints were safety, duration of response, progression-free survival (PFS), and time to progression (TTP).

Results

Of the 54 patients enrolled, 15 (27.8%) completed the study treatment as planned. Intent-to-treat (all enrolled patients) ORR was 72.2% (95% CI: 58.4, 83.5). Median duration of response was 11.9 months (95% CI: 9.3, not estimable) and median TTP was 13.9 months (95% CI: 11.4, 16.0). PFS was virtually the same as TTP. Three (5.6%) patients discontinued therapy due to disease progression, and another 3 (5.6 %) patients discontinued therapy due to serious adverse events (Grade 4 thrombocytopenia, Grade 3 small/large intestinal obstruction/small intestinal perforation, and Grade 3 abdominal abscess). Fifty (92.6%) patients had ≥ 1 adverse event of interest, most commonly neutropenia (42.6%), hypertension (37.0%), stomatitis (37.0%), proteinuria (37.0%), and palmar-plantar erythrodysesthesia (27.8%). No appreciable decreases in left-ventricular ejection fraction were observed.

Conclusion

Most patients responded to PLD, carboplatin, and bevacizumab combination therapy. The safety profile was consistent with the known toxicities of these agents. These findings present a potential treatment option for women with ovarian, fallopian tube, or primary peritoneal cancer.     

Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy

Objective

To evaluate the predictive power of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC).

Methods

Using the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy, and surgical-pathologic information were obtained. Continuous variables were evaluated by Student's t test or Wilcoxon-Mann-Whitney test.

Results

One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749 U/mL and 161 U/mL, respectively. Comparing patients with NRD v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566 U/mL v. 2077 U/mL, p = 0.1). There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233 U/mL (p = 0.001). In the NRD group, 38 patients (80%) had preoperative CA-125 ≤ 100 U/mL compared to 33 patients (63.4%) in the OMD group (p = 0.04).

Conclusions

Patients who undergo NACT-IDS achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤ 100 U/mL were highly likely to be cytoreduced to no residual disease.     

Primary debulking surgery of the upper abdomen and the diaphragm,with a plasma device surgery system,for advanced ovarian cancer

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Objective: Electrically neutral argon plasma (PlasmaJet?) technology is a surgical option that helps to get an aggressive cytoreduction in selected patients with ovarian cancer because it can be directly applied by the surgeon to treat the tissue surface [1,2]. Upper abdominal surgical procedures are an important part of the surgery in these patients [3], there is a 22% complications rate when they are performed [4]. We present a surgical approach to ovarian cancer debulking using PlasmaJet?.Methods: Case history and operative technique: 51 women supported for ovarian cancer Stage IIIC-IV were operated with systematic use of the PlasmaJet device at the Regional Institute Bergonié Cancer Center of Bordeaux, France between June 2012 and June 2014. 41.2% (n = 21) patients underwent a Primary Debulking Surgery (PDS) and 58.8% (n = 30) underwent an Interval Debulking Surgery. 78.4% (n = 40) of the 51 patients studied had a complete cytoreduction. We present the case of a woman diagnosed with a mucinous ovarian carcinoma FIGO stage IVA, who underwent a PDS. Complete cytoreduction to no macroscopic disease was achieved, this included diaphragmatic and abdominal peritoneal stripping.Results: No post-operative complications were found in this case. 15.7% (n = 8) of patients undergoing diaphragmatic stripping with the PlasmaJet required a pleural drain. It is a safe structured procedure, which could be performed to achieve optimal surgical results for patients with ovarian cancer.Conclusions: PlasmaJet? helps the surgeon to perform a peritoneal stripping of the upper abdominal areas and appears to enable the surgeon to remove more disease without increased morbidity, pushing the cytoreduction/morbidity tradeoff.     

A phase II evaluation of nanoparticle, albumin-bound (nab) paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal cancer: a Gynecologic Oncology Group study

Background

Nab-paclitaxel is a novel Cremophor®-free nanoparticle of albumin-stabilized paclitaxel, which has favorable efficacy and toxicity characteristics relative to other solvent-based taxanes, such as paclitaxel and docetaxel.

Methods

Eligible patients had platinum- and taxane-resistant ovarian cancer, defined by persistent or progressive disease following primary chemotherapy (n = 5) or recurrence within 6 months of treatment completion (n = 42). All patients had measurable disease, no prior therapy for recurrent disease and Gynecologic Oncology Group performance status of ≤ 2. Treatment was nab-paclitaxel, 100 mg/m² days 1, 8, and 15 on a 28-day schedule. The primary endpoint was Response Evaluation Criteria in Solid Tumors v1.0 response rate, evaluated in a 2-stage design (with power of 0.90 for a RR of 25% and with alpha of 0.05 for RR of 10%).

Results

Fifty-one patients were enrolled of which 47 were evaluable; median time from frontline therapy completion to registration was 21 days. Patient demographics include median age: 59 (34-78) years, serous histology: 72%, and high-grade: 81%. Efficacy: one complete and 10 partial responses were confirmed (23%); 17 patients (36%) had stable disease. The median progression-free survival was 4.5 months (95% CI: 2.2-6.7); overall survival was 17.4 months (95% CI: 13.2-20.8). Seventeen patients (36%) had PFS >6 months. Toxicity: there were no grade 4 events; grade 3 events were neutropenia (6), anemia (3), GI (2), metabolic (2), pain (2), and leukopenia (1); neurosensory toxicity was observed as grade 2:5, grade 3:1.

Conclusions

Nab-paclitaxel has noteworthy single-agent activity and is tolerable in this cohort of refractory ovarian cancer patients previously treated with paclitaxel.     

Impact of neoadjuvant chemotherapy cycles prior to interval surgery in patients with advanced epithelial ovarian cancer

Objectives

Complete surgery with no macroscopic residual disease (RD) at primary (PDS) or interval debulking surgery (IDS) is the main objective of surgery in advanced epithelial ovarian cancer (EOC). The aim of this work was to evaluate the impact on survival of the number of neoadjuvant chemotherapy (NAC) cycles before IDS in EOC patients.

Methods

Data from EOC patients (stages IIIC–IV), operated on between 1995 and 2010 were consecutively recorded. NAC/IDS patients were analyzed according to the number of preoperative cycles (< 4 = group B1; > 4 = group B2) and compared with patients receiving PDS (group A). Patients with complete resection were specifically analyzed.

Results

367 patients were analyzed, 220 received PDS and 147 had IDS/NAC. In group B, 37 patients received more than 4 NAC cycles (group B2). Group B2 patients presented more frequently stage IV disease at diagnosis (p < 0.01) compared to groups A and B1. The rate of complete cytoreduction was higher in group B (p < 0.001). Patients with no RD after IDS and who had received more than 4 NAC cycles had poor survival (p < 0.001) despite complete removal of their tumor (relative risk of death after multivariate analysis of 3 (p < 0.001)) with an independent impact from disease stage and WHO performance status.

Conclusions

Patients with advanced EOC receiving complete IDS after more than 4 cycles of NAC have poor prognosis. Despite worse prognostic factors observed in this group of patients, our study reinforces the concept of early and complete removal of all macroscopic tumors in the therapeutic sequence of EOC.     

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.