Feasibility of Interval Cytoreduction Following Neoadjuvant Chemotherapy With Carboplatin, Weekly Paclitaxel, and Bevacizumab for Advanced Ovarian Cancer—A Phase 1 Study

2014 ◽  
Vol 24 (4) ◽  
pp. 682-686 ◽  
Author(s):  
Ritu Salani ◽  
David M. O’Malley ◽  
Larry J. Copeland ◽  
David E. Cohn ◽  
Floor J. Backes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Intraoperative Complications ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
Weekly Paclitaxel ◽  
Dosing Schedule ◽  
Repeat Operation ◽  
Interval Cytoreduction

ObjectiveThe objective of this study was to determine a dosing schedule of neoadjuvant chemotherapy using carboplatin, paclitaxel, and bevacizumab in women with advanced ovarian cancer, evaluating feasibility and outcomes from interval cytoreductive surgery (ICS).MethodsUsing a “3+3” design, eligible patients received carboplatin (area under the curve, 5) and bevacizumab (15 mg/kg) every 3 weeks with escalating doses of weekly paclitaxel (60, 70, and 80 mg/m2) for 3 cycles. Patients then received 1 cycle of chemotherapy without bevacizumab followed by ICS. The primary objective was to determine a feasible dosing schedule. Secondary objectives included defining toxicity, response rates based on imaging, and surgical outcomes defined by residual disease following ICS and 30-day postoperative outcomes.ResultsNine patients were enrolled with a median age of 64 years. There were no dose-limiting toxicities, and weekly paclitaxel 80 mg/m2was deemed feasible. During chemotherapy treatment, there were a total of 7 attributable grade 3 toxicities, which most commonly included neutropenia and thromboembolism. All patients demonstrated a response on imaging before surgery, with a median reduction in disease of 56.4% (range, 36.9%–100%). Optimal ICS was performed in all patients, and 78% had no gross residual tumor. There were no intraoperative complications; however, 1 patient experienced an anastomotic leak (grade 4) 10 days after surgery requiring repeat operation.ConclusionsA 4-cycle neoadjuvant regimen of carboplatin area under the curve of 5, weekly paclitaxel 80 mg/m2, and bevacizumab 15 mg/kg for cycles 1 to 3, followed by interval cytoreduction, was feasible. Optimal ICS was achieved in all patients, and surgery was associated with acceptable morbidity.

scholarly journals Incorporating robotic surgery into the management of ovarian cancer after neoadjuvant chemotherapy

2019 ◽  
Vol 29 (9) ◽  
pp. 1341-1347 ◽  
Author(s):  
Jeremie Abitbol ◽  
Walter Gotlieb ◽  
Ziggy Zeng ◽  
Agnihotram Ramanakumar ◽  
Roy Kessous ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Robotic Surgery ◽  
Neoadjuvant Chemotherapy ◽  
Minimally Invasive ◽  
Cytoreductive Surgery ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Stage Iii ◽  
Time Period ◽  
Interval Cytoreduction

IntroductionWith the rapid uptake of robotic surgery in surgical oncology, its use in the treatment of epithelial ovarian cancers is being evaluated. Complete cytoreduction represents the goal of surgery either at primary cytoreduction or after neoadjuvant chemotherapy in the setting of interval cytoreduction. In selected patients, the extent of disease would enable minimally invasive surgery. The objective of this study was to evaluate the impact of introducing robotic surgery for interval cytoreduction of selected patients with stage III–IV ovarian cancer.MethodsAll patients who underwent surgery from November 2008 to 2014 (concurrent time period when robotic and open surgery were used simultaneously) after receiving neoadjuvant chemotherapy for advanced ovarian cancer (stage III–IV) were compared with all consecutive patients who underwent cytoreductive surgery by laparotomy after neoadjuvant chemotherapy between January 2006 and November 2008. Inclusion criteria included an interval cytoreductive surgery by laparotomy or robotic assistance for stage III–IV non-mucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Exclusion criteria included patients treated concurrently for a non-gynecologic cancer, as well as secondary cytoreductive surgeries and diagnostic surgeries without an attempt at tumor reduction. Overall survival, progression-free survival, and peri-operative outcomes were compared for the entire patient cohort with those with advanced ovarian cancer who received neoadjuvant chemotherapy immediately before and after the introduction of robotic surgery.ResultsA total of 91 patients were selected to undergo interval cytoreduction either via robotic surgery (n=57) or laparotomy (n=34) after the administration of neoadjuvant chemotherapy. The median age of the cohort was 65 years (range 24–88), 78% had stage III disease, and the median follow-up time was 37 months (5.6–91.4 months). The median survival was 42.8±3.1 months in the period where both robotic surgery and laparotomy were offered compared with 37.9±9.8 months in the time period preceding when only laparotomy was performed (p=0.6). All patients selected to undergo interval robotic cytoreduction following neoadjuvant chemotherapy had a reduction of cancer antigen 125 by at least 80%, resolution of ascites, and CT findings suggesting the potential to achieve optimal interval cytoreduction. All these patients achieved optimal cytoreduction with <1 cm residual disease, including 82% with no residual disease. The median blood loss was 100 mL (mean 135 mL, range 10–1250 mL), and the median hospital stay was 1 day.ConclusionRobotic interval cytoreductive surgery is feasible in well-selected patients. Future studies should aim to define ideal patients for minimally invasive cytoreductive surgery.

scholarly journals Role of Lymphadenectomy During Interval Debulking Surgery Performed After Neoadjuvant Chemotherapy in Patients With Advanced Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Minjun He ◽  
Yuerong Lai ◽  
Hongyu Peng ◽  
Chongjie Tong
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Debulking Surgery ◽  
Hazard Ratios ◽  
Significant Difference ◽  
Interval Debulking Surgery

ObjectiveThe role of lymphadenectomy in interval debulking surgery (IDS) performed after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer remains unclear. We aimed to investigate the clinical significance of lymphadenectomy in IDS.MethodsWe retrospectively reviewed and analyzed the data of patients with advanced ovarian cancer who underwent NACT followed by IDS.ResultsIn 303 patients receiving NACT-IDS, lymphadenectomy was performed in 127 (41.9%) patients. One hundred and sixty-three (53.8%) patients achieved no gross residual disease (NGRD), and 69 (22.8%) had residual disease &lt; 1 cm, whereas 71 (23.4%) had residual disease ≥ 1cm. No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between the lymphadenectomy group and the no lymphadenectomy group in patients with NGRD, residual disease &lt; 1 cm, and residual disease ≥ 1 cm, respectively. The proportions of pelvic, para-aortic and distant lymph node recurrence were 7.9% (10/127), 4.7% (6/127) and 5.5% (7/127) in the lymphadenectomy group, compared with 5.7% (10/176, P = 0.448), 4.5% (8/176, P = 0.942) and 5.1% (9/176, P = 0.878), respectively, in no lymphadenectomy group. Multivariate analysis identified residual disease ≥ 1 cm [hazard ratios (HR), 4.094; P = 0.008] and elevated CA125 levels after 3 cycles of adjuvant chemotherapy (HR, 2.883; P = 0.004) were negative predictors for OS.ConclusionLymphadenectomy may have no therapeutic value in patients with advanced ovarian cancer underwent NACT-IDS. Our findings may help to better the therapeutic strategy for advanced ovarian cancer. More clinical trials are warranted to further clarify the real role of lymphadenectomy in IDS.

Primary Surgery or Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues…

2016 ◽  
pp. 153-162 ◽  
Author(s):  
Renee Cowan ◽  
Dennis Chi ◽  
Sean Kehoe ◽  
Matthew Nankivell ◽  
Alexandra Leary
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Tumor Biology ◽  
Advanced Ovarian Cancer ◽  
Debulking Surgery ◽  
Primary Debulking Surgery ◽  
Platinum Based Chemotherapy ◽  
Patient Reported ◽  
The Impact

Primary debulking surgery (PDS) followed by platinum-based chemotherapy has been the cornerstone of treatment for advanced ovarian cancer for decades. Primary debulking surgery has been repeatedly identified as one of the key factors in improving survival in patients with advanced ovarian cancer, especially when minimal or no residual disease is left behind. Achieving these results sometimes requires extensive abdominal and pelvic surgical procedures and consultation with other surgical teams. Some clinicians who propose a primary chemotherapy approach reported an increased likelihood of leaving no macroscopic disease after surgery and improved patient-reported outcomes and quality-of-life (QOL) measures. Given the ongoing debate regarding the relative benefit of PDS versus neoadjuvant chemotherapy (NACT), tumor biology may aid in patient selection for each approach. Neoadjuvant chemotherapy offers the opportunity for in vivo chemosensitivity testing. Studies are needed to determine the best way to evaluate the impact of NACT in each individual patient with advanced ovarian cancer. Indeed, the biggest utility of NACT may be in research, where this approach provides the opportunity for the investigation of predictive markers, mechanisms of resistance, and a forum to test novel therapies.

scholarly journals Use and Effectiveness of Neoadjuvant Chemotherapy for Treatment of Ovarian Cancer

2016 ◽  
Vol 34 (32) ◽  
pp. 3854-3863 ◽  
Author(s):  
Larissa A. Meyer ◽  
Angel M. Cronin ◽  
Charlotte C. Sun ◽  
Kristin Bixel ◽  
Michael A. Bookman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Observational Study ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Matched Sample ◽  
Stage Iiic ◽  
Stage Iv Disease ◽  
Postoperative Residual

Purpose In 2010, a randomized clinical trial demonstrated noninferior survival for patients with advanced ovarian cancer who were treated with neoadjuvant chemotherapy (NACT) compared with primary cytoreductive surgery (PCS). We examined the use and effectiveness of NACT in clinical practice. Patients and Methods A multi-institutional observational study of 1,538 women with stages IIIC to IV ovarian cancer who were treated at six National Cancer Institute–designated cancer centers. We examined NACT use in patients who were diagnosed between 2003 and 2012 (N = 1,538) and compared overall survival (OS), morbidity, and postoperative residual disease in a propensity-score matched sample of patients (N = 594). Results NACT use increased from 16% during 2003 to 2010 to 34% during 2011 to 2012 in stage IIIC disease ( Ptrend < .001), and from 41% to 62% in stage IV disease ( Ptrend < .001). Adoption of NACT varied by institution, from 8% to 30% for stage IIIC disease (P < .001) and from 27% to 61% ( P = .007) for stage IV disease during this time period. In the matched sample, NACT was associated with shorter OS in stage IIIC disease (median OS: 33 v 43 months; hazard ratio [HR], 1.40; 95% CI, 1.11 to 1.77) compared with PCS, but not stage IV disease (median OS: 31 v 36 months; HR, 1.16; 95% CI, 0.89 to 1.52). Patients with stages IIIC and IV disease who received NACT were less likely to have ≥ 1 cm postoperative residual disease, an intensive care unit admission, or a rehospitalization (all P ≤ .04) compared with those who received PCS treatment. However, among women with stage IIIC disease who achieved microscopic or ≤ 1 cm postoperative residual disease, NACT was associated with decreased OS (HR, 1.49; 95% CI, 1.01 to 2.18; P = .04). Conclusion Use of NACT increased significantly between 2003 and 2012. In this observational study, PCS was associated with increased survival in stage IIIC, but not stage IV disease. Future studies should prospectively consider the efficacy of NACT by extent of residual disease in unselected patients.

scholarly journals Pre-operative prediction of residual disease after interval cytoreduction for epithelial ovarian cancer using HE4

2019 ◽  
Vol 29 (8) ◽  
pp. 1304-1310
Author(s):  
Pien Lof ◽  
Roelien van de Vrie ◽  
Catharina M Korse ◽  
Willemien J van Driel ◽  
Mignon D J M van Gent ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Residual Disease ◽  
Performance Status ◽  
Area Under The Curve ◽  
Complete Response ◽  
World Health ◽  
Response To Chemotherapy ◽  
Interval Cytoreduction

BackgroundPresence of residual disease after cytoreductive surgery is an important negative prognostic factor for patients with advanced stage epithelial ovarian cancer. Surgery is of limited benefit when the diameter of residual disease is >1 cm. Residual disease is difficult to predict before surgery. The multivariate model Cancer Ovarii Non-invasive Assessment of Treatment Strategy (CONATS) index, based on serum biomarker HE4, age, and World Health Organization performance status, predicted no visible residual disease in patients undergoing primary cytoreductive surgery with an area under the curve (AUC) of 0.85. The AUC of predicting residual disease >1 cm was not reported, although this can be of importance for pre-operative decision making, especially in fragile patients. We tested this model for predicting residual disease >1 cm in patients undergoing interval cytoreduction.MethodsWe retrospectively included patients with advanced epithelial ovarian cancer who underwent interval cytoreduction between January 2010 and December 2017 in two tertiary centers in the Netherlands. HE4 was measured with electrochemiluminescence in pre-operative samples. The CONATS index was used to predict residual disease. AUCs were calculated to predict residual disease >1 cm.ResultsA total of 273 patients were included. Mean (SD) age was 64 (11) years. Median number of cycles of neoadjuvant chemotherapy was 3 (range 3–6) and the most common regimen used consisted of carboplatin and paclitaxel. Before interval cytoreduction, 19 patients (7%) showed complete response to chemotherapy, 251 patients (92%) showed partial response, and 3 patients (1%) showed stable disease at imaging. Following surgery, 232 patients (85%) had residual disease ≤1 cm and 41 patients (15%) had residual disease >1 cm. The AUC was 0.80 for predicting residual disease >1 cm. In patients ≥70 years of age the AUC was 0.82.ConclusionThe CONATS index predicts surgical outcome after interval cytoreduction and is useful in counseling patients about the chance of whether an optimal interval cytoreduction can be achieved. This could be especially helpful in counseling elderly patients in whom surgery has a high risk of complications.

Carboplatin and paclitaxel dose dense as neoadjuvant chemotherapy follow by interval cytoreduction in advanced ovarian cancer.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e16553-e16553 ◽  
Author(s):  
Cindy Alcarraz ◽  
Mivael Olivera ◽  
Johana Muñiz ◽  
Zaida Morante ◽  
Rossana Ruiz ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Ovarian Cancer ◽  
Dose Dense ◽  
Interval Cytoreduction

scholarly journals Evaluation of the feasibility of using weekly paclitaxel as neoadjuvant therapy in patients with epithelial ovarian cancer; a pre-post clinical trial

2020 ◽  
Vol 7 (1) ◽  
pp. e09-e09
Author(s):  
Sakineh Ebrahimi ◽  
Seyed Saeed Hashemi Nazari ◽  
Arash Dooghaie Moghadam ◽  
Shirin Haghighi
Keyword(s):  
Ovarian Cancer ◽  
Clinical Trial ◽  
Side Effects ◽  
Neoadjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Neoadjuvant Therapy ◽  
Advanced Ovarian Cancer ◽  
Response To Treatment ◽  
Weekly Paclitaxel ◽  
Multicenter Studies

Introduction: Although weekly paclitaxel and carboplatin regimen is as effective as the standard method for treatment of advanced ovarian cancer, it has less frequently been used as neoadjuvant therapy. Objectives: To reduce the side effects of typical every three-week chemotherapy and increase progression-free survival (PFS) rate, this study aimed to evaluate the feasibility of using weekly paclitaxel as neoadjuvant therapy in patients with epithelial ovarian cancer. Patients and Methods: This pre-post clinical trial was conducted on 14 patients with stage IIIC (8 patients) and IV (6 patients) advanced ovarian carcinoma. All the patients received the three courses of treatment and then underwent interval debulking surgery. After the surgery, patients received three or five courses based on their stages. Every neoadjuvant chemotherapy course consisted of weekly paclitaxel (80 mg/m2 ) and carboplatin (AUC=6) every 3 weeks. After every 21 days of treatment course, the patients were evaluated to investigate their response to treatment and side effects. Patients were followed up for at least 6 months. Results: The mean (SD) age of the patients was 64±8 years. After three courses of neoadjuvant chemotherapy, one patient (7%) had a complete response and 13 patients (93%) had a partial response. During the treatment period, two patients (14%) developed anemia, one patient (7%) developed neutropenia, two patients (14%) developed thrombocytopenia, and six patients (43%) developed neuropathy. The median (interquartile range) of PFS was 13 months (9.5-16.25). Conclusion: The findings showed that a weekly paclitaxel and carboplatin regimen as neoadjuvant therapy could be effective in the treatment of advanced ovarian cancer. However, it is necessary to conduct multicenter studies with larger sample sizes. Trial registration: Registration of trial protocol has been approved in Iranian Registry of Clinical Trial (identifier: IRCT2017050333789N1; http://en.irct.ir/trial/25978)

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