A randomized multicenter phase II study on neoadjuvant chemotherapy with carboplatin and docetaxel in advanced ovarian carcinomas (PRIMOVAR)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15025-15025 ◽  
Author(s):  
T. Park-Simon ◽  
F. Jänicke ◽  
O. Ortmann ◽  
J. Hilfrich ◽  
G. Breitbach ◽  
...  

15025 Background: In the past years the concept of neoadjuvant chemotherapy and interval laparotomy has emerged for patients with advanced ovarian cancer and unfavorable prognosis (e.g. diffuse peritoneal carcinosis). In a recent study on neoadjuvant chemotherapy higher tumor resection rates and longer median survival were demonstrated in patients with advanced ovarian carcinoma and ascites >500ml. Most studies use three cycles of preoperative chemotherapy. However, chemoresistant tumorclones may be induced by increasing number of preoperative chemotherapy cycles. The purpose of this study is to evaluate the optimal number of cycles prior to interval laparotomy. Methods: 67/73 patients with advanced serous ovarian carcinoma (FIGO IIIc n = 48, FIGO IV n = 19) and ascites >500ml were randomized into two arms, receiving either 2 (n = 33) or 3 (n = 34) cycles of Carboplatin (AUC5) and Docetaxel (75mg/m2) before interval laparotomy. Postoperatively, they received either 4 or 3 additional cycles. Response rate and postoperative residual tumor were evaluated. Results: Surgical response was assessed during interval laparotomy. At present 32 patients underwent tumordebulking. Partial remission was observed in 28/32 patients irrespective of the number of preoperative chemotherapy cycles. Two patients in each arm showed stable disease. Optimal cytoreduction was achieved in 25/32 patients. No severe adverse events were reported. Six of 73 patients were not eligible. Two patients were excluded due to therapy-unrelated events. In 4 patients ovarian cancer was excluded by laparoscopy prior to neoadjuvant chemotherapy. Conclusions: Neoadjuvant chemotherapy followed by interval laparotomy was safe and well tolerated. Diagnostic laparoscopy prior to neoadjuvant chemotherapy allowed differentiation of primary ovarian cancers from tumors of other origin. In these cases laparotomy could be circumvented. Optimal tumor reduction was achieved in a significant number of patients. Response rate and postoperative residual tumor were essentially the same in both arms. Our data indicate that two cycles of preoperative chemotherapy may be the preferential choice of therapy for future studies. No significant financial relationships to disclose.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16036-16036 ◽  
Author(s):  
D. Koensgen ◽  
A. Mustea ◽  
H. Weidemann ◽  
U. Neumann ◽  
P. Neuhaus ◽  
...  

16036 Background: Despite improvement in surgery and adjuvant chemotherapy most pts with ovarian cancer (OC) experience a relapse within 2 years after first diagnosis. For primary OC a standard concensus on optimal staging and surgical guidelines is established. The role of radical tumor debulking surgery in ROC is not clearly defined. Aim of this study was to analyze clinical parameters for prediction of operability and impact on overall survival in ROC. Methods: Within the framework of the international project “Tumor bank Ovarian Cancer“ (TOC) a systematic prospective surgical and histomorphological tumor documentation for ROC was performed. Results: Between september 2000 and december 2006, 307 multivisceral operations on 254 pts with ROC were performed consecutively in our department. Median age was 55 years (19–83), median follow-up 15 months (1–75). 34.8% of pts experienced first relapse of OC. Overall, 96.3% of pts received a platinum-based first-line chemotherapy, whereas 73.4% were platinum sensitive. In 55% of pts first relapse surgery was performed. In 41.4% of pts complete macroscopic tumor resection was achieved, associated with a significantly better recurrence-free (median 20.6 vs 13.2, p=0.001) and overall survival (median 42 vs 12 months, p<0.001) compared to pts with any postoperative residual tumor. In multivariate analysis, complete tumor resection was associated with the absence of tumor burden in the upper abdomen (p=0.001) and absence of ascites (p=0.05). Prognostic factors for postoperative survival were: tumor resection (0 cm vs > 0 cm, p<0.001), intraoperative volume of ascites (0 ml vs > 0 ml, p=0.006) and response to platinum-based first-line therapy (platinum sensitive vs platinum-resistant, p=0.006). Conclusions: Radical tumor debulking in patients with ROC is associated with a low postoperative morbidity and mortality. Complete mascroscopic tumor resection is correlated with a significant better long-term prognosis and influenced by tumor spread and presence of ascites. Pts with ROC will not benefit from multivisceral cytoreductive surgery in case of platinum resistance to first-line chemotherapy, presence of intraoperative ascites and postoperative residual tumor. No significant financial relationships to disclose.


2019 ◽  
Vol 65 (1) ◽  
pp. 56-62
Author(s):  
Alisa Villert ◽  
Larisa Kolomiets ◽  
Natalya Yunusova ◽  
Yevgeniya Fesik

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.


2018 ◽  
Vol 78 (10) ◽  
pp. 972-976 ◽  
Author(s):  
Enzo Ricciardi ◽  
Thaïs Baert ◽  
Beyhan Ataseven ◽  
Florian Heitz ◽  
Sonia Prader ◽  
...  

AbstractIn the early 2000s a two-tier grading system was introduced for serous ovarian cancer. Since then, we have increasingly come to accept that low-grade serous ovarian carcinoma (LGSOC) is a separate entity with a unique mutational landscape and clinical behaviour. As less than 10% of serous carcinomas of the ovary are low-grade, they are present in only a small number of patients in clinical trials for ovarian cancer. Therefore the current treatment of LGSOC is based on smaller trials, retrospective series, and subgroup analysis of large clinical trials on ovarian cancer. Surgery plays a major role in the treatment of patients with LGSOC. In the systemic treatment of LGSOC, hormonal treatment and targeted therapies seem to play an important role.


2021 ◽  
Author(s):  
Mukur Dipi Ray ◽  
Suryanarayana S.V. Deo ◽  
Lalit Kumar ◽  
Manish Kumar Gaur

In cases of ovarian carcinoma, primary cytoreductive surgery (CRS) is the standard treatment up to stage IIIB, but patient selection for neoadjuvant chemotherapy (NACT) in selected cases is controversial. A total of 200 patients with advanced ovarian cancer were analyzed retrospectively, according to specific selection criteria. Primary CRS was performed in 95 patients (47.5%) and interval CRS after 3–6 cycles of NACT was performed in 105 patients (52.5%). After median follow-up of 35 months, 5-year overall survival was 53.7% in the upfront CRS group and 42.2% in the NACT group. Primary CRS is the standard in advanced stages of ovarian carcinoma, but in certain subset of patients, NACT is preferred. Identifying that group is challenging but feasible. Proper selection of patients is key to successful outcomes.


2005 ◽  
Vol 15 (2) ◽  
pp. 217-223 ◽  
Author(s):  
V. Loizzi ◽  
G. Cormio ◽  
L. Resta ◽  
C. A. Rossi ◽  
A. R. Di Gilio ◽  
...  

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.


2019 ◽  
Vol 29 (6) ◽  
pp. 1050-1056 ◽  
Author(s):  
Yolanda Garcia Garcia ◽  
Ana de Juan Ferré ◽  
Cesar Mendiola ◽  
Maria-Pilar Barretina-Ginesta ◽  
Lydia Gaba Garcia ◽  
...  

BackgroundBevacizumab is an approved treatment after primary debulking surgery for ovarian cancer. However, there is limited information on bevacizumab added to neoadjuvant chemotherapy before interval debulking surgery.ObjectiveTo evaluate neoadjuvant bevacizumab in a randomized phase II trial.MethodsPatients with newly diagnosed stage III/IV high-grade serous/endometrioid ovarian cancer were randomized to receive four cycles of neoadjuvant chemotherapy with or without ≥3 cycles of bevacizumab 15 mg/kg every 3 weeks. After interval debulking surgery, all patients received post-operative chemotherapy (three cycles) and bevacizumab for 15 months. The primary end point was complete macroscopic response rate at interval debulking surgery.ResultsOf 68 patients randomized, 64 completed four neoadjuvant cycles; 22 of 33 (67%) in the chemotherapy-alone arm and 31 of 35 (89%) in the bevacizumab arm (p=0.029) underwent surgery. The complete macroscopic response rate did not differ between treatment arms in either the intention-to-treat population of 68 patients (6.1% vs 5.7%, respectively; p=0.25) or the 55 patients who underwent surgery (8.3% vs 6.5%; p=1.00). There was no difference in complete cytoreduction rate or progression-free survival between the treatment arms. During neoadjuvant therapy, grade ≥3 adverse events were more common with chemotherapy alone than with bevacizumab (61% vs 29%, respectively; p=0.008). Intestinal (sub)occlusion, fatigue/asthenia, abdominal infection, and thrombocytopenia were less frequent with bevacizumab. The incidence of grade ≥3 adverse events was 9% in the control arm versus 16% in the experimental arm in the month after surgery.ConclusionsAdding three to four pre-operative cycles of bevacizumab to neoadjuvant chemotherapy for unresectable disease did not improve the complete macroscopic response rate or surgical outcome, but improved surgical operability without increasing toxicity. These results support the early integration of bevacizumab in carefully selected high-risk patients requiring neoadjuvant chemotherapy for initially unresectable ovarian cancer.


2003 ◽  
Vol 19 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Cristina Rodríguez-Burford ◽  
David C. Chhieng ◽  
Cecil R. Stockard ◽  
Marc J. Kleinberg ◽  
Mack N. Barnes ◽  
...  

Ovarian cancer has a high mortality rate largely due to the limited number of ovarian carcinomas detected at an early stage. Understanding the molecular changes occurring during the progression of ovarian carcinoma would aid in the development of therapies that may inhibit or target metastasis. Primary and metastatic lesions from 54 and 40 patients with advanced ovarian carcinoma, respectively (including matched primary and metastatic lesions from 30 patients) were evaluated for nuclear accumulation of p53 (clone BP53-12-1) and cytoplasmic and membranous immunostaining of p185 erbB-2 (clone 3B5) by immunohistochemistry. No differences in the immunostaining of p53 and p185erbB-2 (cytoplasm or membrane) were observed between primary and metastatic lesions of the matched cases. Similarly, no differences in the proportion of positive cases of p53 between primary and metastatic lesions of the matched cases was observed. Thus, novel therapies that target p53 or p185erbB-2 can utilize specimens from either primary or metastatic lesions to characterize these targets prior to therapy. Spearman correlations between p53 and p185erbB-2 (cytoplasm or membrane) immunohistochemistry scores were insignificant for the matched cases, all primary lesions, and all metastatic lesions. Also, no significant associations occurred between nuclear accumulation of p53 (positive versus negative) and phenotypic expression of p185erbB-2 (cytoplasm or membrane) immunostaining scores for the matched cases, all primary lesions, and all metastatic lesions. Thus, the nuclear accumulation of p53 and immunostaining of p185erbB-2 in the cytoplasm or on the cellular membranes are independent.


1990 ◽  
Vol 5 (3) ◽  
pp. 103-108 ◽  
Author(s):  
F. Crippa ◽  
M. Presti ◽  
A. Marini ◽  
B. D'Onofrio ◽  
G. Bolis ◽  
...  

Twenty-five patients treated with debulking surgery and chemotherapy for ovarian cancer were prospectively studied to evaluate the efficacy of radioimmunoscintigraphy (RIS) in detecting residual tumor before second-look surgery. RIS was performed with the monoclonal antibody OC125 F(ab')2 labelled with 1-131 without knowledge of clinical data and compared with subsequent surgical results. Second look showed tumor persistence in 12 patients, mostly characterized by small lesions. The overall diagnostic sensitivity of RIS was 50% and the specificity was 85%. In particular, RIS showed better sensitivity for pelvic tumor localizations than for abdominal sites (73% vs 33%); this was due to the inability of RIS to detect upper abdominal lesions. Therefore, our conclusion is that, at present, RIS cannot substitute surgical second-look in the management of ovarian cancer, however, considering that also ultrasonography, computer tomography and magnetic resonance are not always able to give definite diagnostic evidence in the follow-up of ovarian carcinoma, RIS could be added to these procedures to balance the limitations of each method. In this regard, the best application of RIS could be in the follow-up of patients with marker elevation without clinical evidence of disease, especially in the case of pelvic fibrosis or adhesions due to previous therapy, where the other non-invasive tools can give doubtful diagnostic results.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5512-5512
Author(s):  
D. de Jong ◽  
J. E. Dodge ◽  
O. Freedman ◽  
E. Lo ◽  
B. P. Rosen ◽  
...  

5512 Background: Neoadjuvant chemotherapy (NAC) is increasingly used to treat patients (pts) with presumed advanced-stage epithelial ovarian cancer (EOC) who are deemed ineligible for upfront debulking surgery (DS). DS following NAC offers a survival benefit to those pts in whom optimal cytoreduction (< 1 cm residual tumor) is achieved. However, not all women who commence NAC have a subsequent attempt at DS. The aims of this study were to identify, in pts planned for NAC, predictive parameters for attempting DS and for achieving optimal cytoreduction in those undergoing surgery. Methods: Pts with presumed stage IIIC or IV EOC who started NAC between 1998 and 2004 were selected for chart review from our institutional ovarian cancer database. Pts with synchronous primary tumors or final pathology inconsistent with EOC were excluded. Age, presence of ascites, Pre NAC hemoglobin (Hb), platelet count (Pls), and CA-125 were explored as possible predictors of attempting DS and of optimal cytoreduction using Kruskal-Wallis analysis and multivariate regression analysis with backward elimination. Results: 212 pts met inclusion criteria. 164 pts (77.4%) had an attempt at DS after NAC; of these 109 pts (66.4%) were optimally cytoreduced. Age and pre-NAC Pls were independent predictors for attempting DS. Median age of pts undergoing DS was 65 years (range 42–82 yrs) compared to 77 yrs (range 54–89 yrs) in those in whom there was no DS attempt, p < 0.01. Median pre NAC Pls of pts undergoing DS was 398 (range 220–685) *109/L, compared to 298 (178–519) for those not proceeding to DS, p < 0.001. Pre NAC Hb, CA125, and ascites were not predictors of DS. Among pts undergoing DS, age was the only independent predictor of optimal cytoreduction identified: median age of pts (optimal vs. suboptimal cytoreduction) was 57yrs (range 42–73 yrs) vs. 67 yrs (49–82yrs), p < 0.001. Presence of ascites, pre-NAC Hb, pre-NAC Pls, and pre-NAC CA-125 were not predictors of optimal cytoreduction. Conclusions: At our centre, pt age and pre-NAC Pls are independent predictors for attempting DS following NAC for advanced stage EOC. In pts undergoing DS age was the only independent predictor of optimal cytoreduction identified. Further investigation of these findings is warranted. No significant financial relationships to disclose.


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