Primary Chemotherapy: The Future for the Management of Advanced Ovarian Cancer?

2010 ◽  
Vol 20 (Suppl 2) ◽  
pp. S17-S19 ◽  
Author(s):  
Jonathan A. Ledermann
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Primary Chemotherapy ◽  
Biological Behavior ◽  
Preoperative Imaging ◽  
Primary Surgery ◽  
Platinum Based Chemotherapy ◽  
Tumor Debulking

Primary surgery for advanced ovarian cancer has been the standard practice for more than 30 years. A survival benefit is principally seen in patients who have optimal cytoreduction with no or small-volume residual disease after surgery. In everyday clinical practice, many patients are not able to undergo optimal tumor debulking. Modern preoperative imaging and assessment can identify most of these patients. Through developments in platinum-based chemotherapy, a high proportion of patients can be expected to respond to primary (neoadjuvant) chemotherapy. A recent clinical trial has shown that the survival of patients with operable disease is not disadvantaged by neoadjuvant chemotherapy followed by surgery. Thus, complete tumor cytoreduction could be achieved in a greater percentage of patients, if primary chemotherapy is used in women in whom optimal primary surgery would be difficult. Furthermore, delayed surgery provides more knowledge about the biological behavior of the tumor, and this could be used to tailor treatment more effectively.

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

2006 ◽  
Vol 16 (Suppl 1) ◽  
pp. 47-53 ◽  
Author(s):  
H. Steed ◽  
A. M. Oza ◽  
J. Murphy ◽  
S. Laframboise ◽  
G. Lockwood ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Retrospective Analysis ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Postoperative Chemotherapy ◽  
Pleural Effusions ◽  
Primary Surgery ◽  
Platinum Based Chemotherapy ◽  
Significant Difference

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.

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 Relationship Between Time Interval From Primary Surgery to the Start of Taxane- Plus Platinum-Based Chemotherapy and Clinical Outcome of Patients With Advanced Epithelial Ovarian Cancer: Results of a Multicenter Retrospective Italian Study

2005 ◽  
Vol 23 (4) ◽  
pp. 751-758 ◽  
Author(s):  
Angiolo Gadducci ◽  
Enrico Sartori ◽  
Fabio Landoni ◽  
Paolo Zola ◽  
Tiziano Maggino ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Complete Response ◽  
Time Interval ◽  
Primary Surgery ◽  
Second Look ◽  
Platinum Based Chemotherapy

Purpose To assess whether the interval from primary surgery to the start of taxane- plus platinum-based chemotherapy has any impact on the clinical outcome of advanced ovarian cancer patients. Patients and Methods The study was conducted on 313 patients who underwent surgery followed by taxane- plus platinum-based chemotherapy. The median follow-up of survivors was 30.7 months (range, 6 to 109 months). Results The 25%, 50%, and 75% quantiles of intervals from surgery to the start of chemotherapy were 11, 21, and 31 days, respectively. After the sixth cycle, 102 patients achieved a pathologic complete response at second-look surgery and 98 obtained a clinical complete response but were not submitted to second-look surgery. Taking into consideration the best assessed response, a complete (either clinical or pathologic) response was found in 200 patients. Residual disease (≤ 1 v > 1 cm; P < .0001) and ascites (absent v present; P = .003) were independent predictive factors for achieving a complete response, whereas residual disease (P = .001) and stage (IIc to III v IV; P = .04) were independent prognostic variables for survival. Conversely, statistical analyses failed to detect significant differences in complete response rates and survival among patients with an interval from surgery to chemotherapy shorter than 11 days, 12 to 21 days, 22 to 31 days, and longer than 31 days. Conclusion The interval from surgery to the start of taxane- plus platinum-based chemotherapy seems to have neither a predictive value for response to treatment nor a prognostic relevance for survival of advanced ovarian cancer patients.

TRUST: Trial of Radical Upfront Surgical Therapy in advanced ovarian cancer (ENGOT ov33/AGO‐OVAR OP7)

2019 ◽  
Vol 29 (8) ◽  
pp. 1327-1331 ◽  
Author(s):  
Alexander Reuss ◽  
Andreas du Bois ◽  
Philipp Harter ◽  
Christina Fotopoulou ◽  
Jalid Sehouli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cytoreductive Surgery ◽  
Advanced Ovarian Cancer ◽  
Figo Stage ◽  
Complete Resection ◽  
Peritoneal Carcinoma ◽  
Exclusion Criteria ◽  
Platinum Based Chemotherapy

BackgroundPrimary cytoreductive surgery followed by chemotherapy has been considered standard management for patients with advanced ovarian cancer over decades. An alternative approach of interval debulking surgery following neoadjuvant chemotherapy was subsequently reported by two randomized phase III trials (EORTC‐GCG, CHORUS), which were criticized owing to important limitations, especially regarding the rate of complete resection.Primary ObjectiveTo clarify the optimal timing of surgical therapy in advanced ovarian cancer.Study HypothesisPrimary cytoreductive surgery is superior to interval cytoreductive surgery following neoadjuvant chemotherapy for overall survival in patients with advanced ovarian cancer.Trial DesignTRUST is an international open, randomized, controlled multi-center trial investigating overall survival after primary cytoreductive surgery versus neoadjuvant chemotherapy and subsequent interval cytoreductive surgery in patients with FIGO stage IIIB–IVB ovarian, tubal, and peritoneal carcinoma. To guarantee adequate surgical quality, participating centers need to fulfill specific quality assurance criteria (eg, ≥50% complete resection rate in upfront surgery for FIGO IIIB–IVB patients, ≥36 debulking-surgeries/year) and agree to independent audits by TRUST quality committee delegates. Patients in the primary cytoreductive surgery arm undergo surgery followed by 6 cycles of platinum-based chemotherapy, whereas patients in the interval cytoreductive surgery arm undergo 3 cycles of neoadjuvant chemotherapy after histologic confirmation of the disease, followed by interval cytoreductive surgery and subsequently, 3 cycles of platinum-based chemotherapy. The intention of surgery for both groups is complete tumor resection according to guideline recommendations.Major Inclusion/Exclusion CriteriaMajor inclusion criteria are suspected or histologically confirmed, newly diagnosed invasive epithelial ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma FIGO stage IIIB–IVB (IV only if resectable metastasis). Major exclusion criteria are non-epithelial ovarian malignancies and borderline tumors; prior chemotherapy for ovarian cancer; or abdominal/pelvic radiotherapy.Primary EndpointOverall survival.Sample Size772 patients.Estimated Dates for Completing Accrual and Presenting ResultsAccrual completion approximately mid-2019, results are expected after 5 years' follow-up in 2024.Trial RegistrationNCT02828618.

scholarly journals New Challenges in Tumor Mutation Heterogeneity in Advanced Ovarian Cancer by a Targeted Next-Generation Sequencing (NGS) Approach

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 584 ◽  
Author(s):  
Marica Garziera ◽  
Rossana Roncato ◽  
Marcella Montico ◽  
Elena De Mattia ◽  
Sara Gagno ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Next Generation Sequencing ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Genetic Profile ◽  
Next Generation ◽  
Platinum Based Chemotherapy ◽  
Targeted Ngs ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Next-generation sequencing (NGS) technology has advanced knowledge of the genomic landscape of ovarian cancer, leading to an innovative molecular classification of the disease. However, patient survival and response to platinum-based treatments are still not predictable based on the tumor genetic profile. This retrospective study characterized the repertoire of somatic mutations in advanced ovarian cancer to identify tumor genetic markers predictive of platinum chemo-resistance and prognosis. Using targeted NGS, 79 primary advanced (III–IV stage, tumor grade G2-3) ovarian cancer tumors, including 64 high-grade serous ovarian cancers (HGSOCs), were screened with a 26 cancer-genes panel. Patients, enrolled between 1995 and 2011, underwent primary debulking surgery (PDS) with optimal residual disease (RD < 1 cm) and platinum-based chemotherapy as first-line treatment. We found a heterogeneous mutational landscape in some uncommon ovarian histotypes and in HGSOC tumor samples with relevance in predicting platinum sensitivity. In particular, we identified a poor prognostic signature in patients with HGSOC harboring concurrent mutations in two driver actionable genes of the panel. The tumor heterogeneity described, sheds light on the translational potential of targeted NGS approach for the identification of subgroups of patients with distinct therapeutic vulnerabilities, that are modulated by the specific mutational profile expressed by the ovarian tumor.

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.

scholarly journals Significance of Platinum Distribution to Predicts Platinum Resistance in Ovarian Cancer After Platinum Treatment in Neoadjuvant Chemotherapy

2021 ◽  
Author(s):  
Kaname Uno ◽  
Nobuhisa Yoshikawa ◽  
Akira Tazaki ◽  
Shoko Ohnuma ◽  
Kazuhisa Kitami ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Inductively Coupled Plasma ◽  
Advanced Ovarian Cancer ◽  
Type A ◽  
Platinum Resistance ◽  
Tumor Type ◽  
Platinum Based Chemotherapy ◽  
Platinum Accumulation

Abstract Most advanced ovarian cancer patients experience recurrence and develop resistance to platinum-based agents. However, the diagnosis of platinum resistance based on platinum-free interval is not always accurate and timely. In this study, we employed laser ablation inductively coupled plasma mass spectrometry to visualize platinum distribution in the tissues at the time of interval debulking surgery following neoadjuvant chemotherapy. Twenty seven patients with advanced high grade serous ovarian cancer were enrolled. Two distinct patterns of platinum distribution were observed. Type A (n = 16): platinum accumulation at the adjacent stroma but little in the tumor; type B (n = 11): even distribution of platinum through tumor and adjacent stroma. Type A was significantly correlated with worse prognosis (P = 0.031). Patients classified in type A and treated with platinum-based adjuvant chemotherapy after operation were significantly shorter period of recurrence after last platinum-based chemotherapy (P = 0.020) and diagnosed with “platinum-resistant recurrence”. Treatment with non-platinum-based chemotherapy after operation could be effective for the patients who were classified in type A. Our data indicate that the platinum resistance can be predicted prior to recurrence with platinum distribution. Thus, we will be able to select more appropriate adjuvant chemotherapy, which may possibly lead to improve patient’s prognosis.

Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness

2014 ◽  
Vol 132 (2) ◽  
pp. 287-291 ◽  
Author(s):  
Vanessa da Costa Miranda ◽  
Ângelo Bezerra de Souza Fêde ◽  
Carlos Henrique dos Anjos ◽  
Juliana Ribeiro da Silva ◽  
Fernando Barbosa Sanchez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Advanced Ovarian Cancer ◽  
Primary Surgery

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.

Sign in / Sign up

Export Citation Format

Share Document