Dose-dense early postoperative intraperitoneal chemotherapy in ovarian cancer: Randomized, phase II trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5514-5514
Author(s):  
Rongyu Zang ◽  
Tingyan Shi ◽  
Rong Jiang ◽  
Hong Pu ◽  
Huijuan Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Wild Type ◽  
Phase 2 Trial ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Dose Dense ◽  
Optimal Debulking ◽  
A Prospective Study

5514 Background: Dose-dense early postoperative intraperitoneal chemo (DD-EPIC) had been carried out in advanced ovarian cancer (OC) pts in China over the past three decades but it was not proved by a prospective study. This trial was designed to confirm the benefit of DD-EPIC in delaying progression and improving survival. Methods: In a multicenter, phase 2 trial, pts with FIGO IIIC-IV OC and optimal debulking surgery (residual disease ≤1cm) were randomly allocated to receive 4 doses of weekly DD-EPIC with cisplatin (50mg/m2) and etoposide (100mg/m2) followed by 6 cycles of intravenous (iv) chemo with carboplatin and taxane every 3 weeks (DD-EPIC group), or standard iv chemo alone (iv group). (ClinicalTrials.gov, NCT01669226). Results: Between 2009 and 2015, 218 pts were randomized, of whom 215 initiated treatment (106 to DD-EPIC and 109 to iv; for efficacy analyses). Totally, 36 pts (16·7%) were received neoadjuvant chemo. With a median of 61·9 mos follow-up, 122 pts died (54 in DD-EPIC and 68 in iv group). Remarkable OS benefit of DD-EPIC was recorded (67·5 mos for DD-EPIC vs. 46·3 mos for iv; HR 0·70, 95% CI 0·49-1·00, P=0·047). Pts in DD-EPIC had a significantly increased median PFS compared with those in iv group (21·7 vs. 16·8 mos; HR 0·64, 95% CI 0·47-0·86, P=0·003). Median TFST was 25·1 vs. 18·0 mos in favor of DD-EPIC (HR 0·62, 95%CI 0·46-0·83, P=0·002). Similar findings were detected in TSST (42·2 vs. 29·3 mos; HR 0·66, 95%CI 0·47-0·94, P=0·019). Grade 3 and 4 Leucopenia (53·8% vs. 35·2%), anemia (23·6% vs. 5·6%) and gastrointestinal events (10·4% vs. 1·9%) were more common in DD-EPIC ( P=0·006, P<0·001 and P=0·010, respectively). Ninety-one pts were detected by gBRCA testing, with 25·3% of cases carrying deleterious BRCAm, but PFS and OS benefit were observed in patients with BRCA-wild type (HR 0·46 and 0·55, 95%CI 0·27-0·81 and 0·27-1·11, respectively). Conclusions: DD-EPIC with a higher completion rate and acceptable treatment burden was associated with longer OS than standard iv alone. Owing to the benefit of relatively long-term OS, DD-EPIC may be considered as a valuable option for OC, particularly in developing countries and BRCA-wild type pts. Clinical trial information: NCT01669226. [Table: see text]

The rate and role of diaphragmatic peritonectomy in optimal cytoreduction in patients with advanced stage ovarian cancer: a prospective study of 100 patients

2014 ◽  
Vol 21 (1) ◽  
pp. 1-7
Author(s):  
Tomas Lūža ◽  
Agnė Ožalinskaitė ◽  
Vilius Rudaitis
Keyword(s):  
Ovarian Cancer ◽  
Confidence Interval ◽  
Cytoreductive Surgery ◽  
Residual Disease ◽  
Advanced Ovarian Cancer ◽  
Optimal Cytoreduction ◽  
Entire Cohort ◽  
Kaplan Meier ◽  
Upper Abdominal ◽  
A Prospective Study

Background. Diaphragmatic peritoneal metastasis by advanced epi­thelial ovarian cancer is a very common holdback precluding optimal cytoreduction. The aim of this study was to determine the rate of dia­phragmatic peritonectomy during optimal cytoreductive surgery and its role in postoperative morbidity and survival in patients with advanced ovarian cancer. Materials and methods. 100 consecutive patients with advanced epithelial ovarian cancer underwent cytoreductive surgery and were followed up prospectively (January 2009 – March 2014). Characteristics of surgery, rate of diaphragmatic peritonectomy and post operative complications were assessed. The Kaplan-Meier method was used for survival analysis. Results. The median age of the entire cohort at the time of primary cytoreduction was 58.5 years (23–83). Optimal cytoreduction was achieved in 73 cases out of 100 patients. From 73 patients in 30 cases (41.1%) upper abdominal procedures, specifically diaphragmatic peritonectomy, was performed to achieve the main goal of cytoreduction  –  no visible or palbable disease at the end of cytoreduction. Non-optimal cytoreduction was achieved in 27 cases. According to the Clavien-Dindo complication grading system grade I and grade II complications occurred more often in patients that underwent diaphragmatic surgery. The median overall survival from the time of diagnosis to the last follow-up or death was 28 months (range 0–63 months). The factors associated with the longest survival after primary cytoreductive surgery were the disease free interval from the primary cytoreduction of more than 19 months (n = 51) versus less than 19 months (n = 49) (95% confidence interval, 51.7–59.5; P = 0.013) and no visible or palpable residual disease at the end of cytoreduction (n = 73) versus visible or palpable residual di­sease (n = 27) (95% confidence interval, 52.7–61.2; P = 0.03). Conclusions. Based on our prospective analysis of advanced ovarian cancer patients, diaphragmatic peritonectomy is feasible and safe, ensures better rates of optimal cytoreduction and should not be an obstacle towards better survival.

Efficacy of dose-dense chemotherapy as first-line treatment of advanced ovarian cancer patients after non-optimal debulking.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e18066-e18066
Author(s):  
Alexey Rumyantsev ◽  
Alexandra Tyulyandina ◽  
Ilya Pokataev ◽  
Konstantin Morkhov ◽  
Valentina Mikhailovna Nechuskina ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Advanced Ovarian Cancer ◽  
Residual Tumor ◽  
Severe Neutropenia ◽  
Front Line ◽  
Debulking Surgery ◽  
Dose Dense ◽  
Optimal Debulking

e18066 Background: Patients with advanced ovarian cancer have unfavorable prognosis after primary debulking surgery if the size of residual tumor exceeds 1 cm. The optimal approaches to systemic treatment of these patients remain unknown. We evaluated the efficacy and safety of dose-dose chemotherapy in frontline treatment of ovarian cancer patients after upfront non-optimal debulking surgery. Methods: This was a non-randomized single-arm phase II trial. We enrolled patients with advanced (FIGO III-IV) epithelial ovarian who underwent non-optimal upfront debulking surgery with residual tumor size > 10 mm. All patients were treated with dose-dense chemotherapy (ie, paclitaxel 80 mg/m2 day 1, 8, 15 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles). Patients in historical control arm received standard chemotherapy with paclitaxel 175 mg/m2 day 1 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles. No patient in experimental or control arm received front-line bevacizumab or PARP inhibitors. The primary endpoint of the trial was progression-free survival (PFS). According to the historical data of our department, 1-year PFS in this category of patients equals to 51%. To increase 1-year PFS to 70%, 40 patients should be enrolled with α = 0.05 and β = 0.20 and estimated data loss for 10% of patients. Results: The study enrolled 40 patients to dose-dense chemotherapy arm, control arm included 86 patients. The trial arms were balanced in terms of age, performance status and other characteristics. Median follow-up was 28.8 months. The 1-year PFS was 76.9% compared to 51% in historical arm, median PFS was 19.8 months and 12 months respectively (HR 0.61; 95% CI 0.39-0.95; p = 0,03). The 1-year overall survival rate was 92.3% with median OS not reached with specified follow-up period. Severe neutropenia, anemia, thrombocytopenia was observed in 82.1%, 53.8%, 15.3% of patients, respectively. Conclusions: The results of the study showed high efficacy of dose-dose chemotherapy as front line of treatment for advanced ovarian cancer patients after non-optimal upfront debulking surgery but one should consider high toxicity of this regimen.

The Prognostic Impact of the Pathological Response to Neoadjuvant Dose-Dense Therapy for Ovarian Carcinoma

2017 ◽  
Vol 27 (9) ◽  
pp. 1850-1855 ◽  
Author(s):  
Takahiro Ebata ◽  
Mayu Yunokawa ◽  
Hiroshi Yoshida ◽  
Seiko Bun ◽  
Tatsunori Shimoi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Factors ◽  
Tumor Cells ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Complete Response ◽  
Pathological Response ◽  
Prognostic Impact ◽  
Grade 3 ◽  
Dose Dense

ObjectiveThe aim of this study was to assess the use of the pathological response to neoadjuvant chemotherapy (NAC) for predicting disease prognosis in patients with advanced ovarian cancer who received neoadjuvant dose-dense weekly paclitaxel and carboplatin (dd-TC) therapy.MethodsWe retrospectively investigated patients with advanced epithelial ovarian, tubal, or peritoneal carcinoma treated at our hospital from July 2004 to October 2014. Patients received dd-TC therapy as NAC followed by interval debulking surgery (IDS). Specimens resected during IDS were divided into 4 groups based on pathological response: grade 1, most tumor cells appeared to be viable; grade 2a, most tumor cells had disappeared, whereas the remaining tumor cells were vacuolated or degenerated; grade 2b, small numbers of viable tumor cells were observed; and grade 3, small aggregations of macrophages were seen.ResultsSixty-eight patients were enrolled. The median number of NAC cycles was 3 (range, 2–6), and 51 patients (75.0%) achieved complete resection at IDS. Regarding pathological response, 7 (10.3%) patients were classified as grade 1, 11 (16.2%) as grade 2a, 46 (67.7%) as grade 2b, and 4 (5.9%) as grade 3. In univariate and multivariate analyses, grades 2b and 3 pathological responses were significant favorable prognostic factors for progression-free survival (P = 0.028; hazard ratio, 0.48; 95% confidence interval, 0.26–0.92).ConclusionsAlthough the pathological complete response rate to NAC was low in this study, both complete and good pathological responses to NAC might be favorable prognostic factors for PFS in patients with advanced ovarian cancer who receive dd-TC.

scholarly journals The Role of Ultra-Radical Surgery in the Management of Advanced Ovarian Cancer: State or Art

2021 ◽  
Author(s):  
Felicia Elena Buruiana ◽  
Lamiese Ismail ◽  
Federico Ferrari ◽  
Hooman Soleymani Majd
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Radical Surgery ◽  
Advanced Ovarian Cancer ◽  
Holistic Approach ◽  
Gynaecological Malignancy ◽  
Optimal Debulking ◽  
Upper Abdomen ◽  
The Impact

The ovarian cancer, also known as “silent killer”, has remained the most lethal gynaecological malignancy. The single independent risk factor linked with improved survival is maximum cytoreductive effort resulting in no macroscopic residual disease. This could be gained through ultra-radical surgery which demands tackling significant tumour burden in pelvis, lower and upper abdomen which usually constitutes bowel resection, liver mobilisation, ancillary cholecystectomy, extensive peritonectomy, diaphragmatic resection, splenectomy, resection of enlarged pelvic, paraaortic, and rarely cardio-phrenic lymph nodes in order to achieve optimal debulking. The above can be achieved through a holistic approach to patient’s care, meticulous patient selection, and full engagement of the family. The decision needs to be carefully balanced after obtaining an informed consent, and an appreciation of the impact of such surgery on the quality of life against the survival benefit. This chapter will describe the complexity and surgical challenges in the management of advanced ovarian cancer.

Correlative study of low serum creatinine and hematological toxicities in Japanese patients with ovarian cancer treated by dose dense TC therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5045-5045
Author(s):  
Koji Matsumoto ◽  
Takuma Onoe ◽  
Akihito Kitao ◽  
Maki Tanioka ◽  
Shunichi Negoro
Keyword(s):  
Ovarian Cancer ◽  
Serum Creatinine ◽  
Advanced Ovarian Cancer ◽  
Japanese Patients ◽  
Enzymatic Assays ◽  
Minimum Value ◽  
Gault Formula ◽  
Grade 3 ◽  
Dose Dense ◽  
Low Serum

5045 Background: Dose dense TC (ddTC) is a novel standard therapy for patients (pts) with advanced ovarian cancer, although hematological toxicities (hemTX), especially anemia, may increase as observed in NOVEL trial (JGOG3016). Low serum creatinine (LCr), especially below 0.7 mg/dl, may lead to overestimation of GFR. GOG announced that pts with LCr should use a minimum value of 0.7mg/dl to estimate GFR. The correlation between LCr and hemTX treated by ddTC is unknown. Methods: GFR was determined using the Cockcroft-Gault formula. Serum creatinine concentrations were measured using enzymatic assays. Minimum value of 0.7 mg/dl was not used during this period of time. The carboplatin clearance was then calculated by Calvert equation. HemTX were defined as, Grade 3 or 4 (by CTC-AE ver.4) neutropenia, anemia, and thrombocytopenia. Using electrical chart, frequency of hemTX and correlation between serum creatinine (less than 0.7 or not) were examined. Results: From Feb. 2010 to Dec. 2011, 61 consecutive pts were treated with ddTC. LCr was observed in 73% of pts. No treatment related death occurred. Among 61 pts, 50 (82%), 31 (51%), and 12 (19.6 %) pts experienced Grade3/4 neutropenia, anemia and thrombocytopenia, respectively. HemTX in pts with LCr and the others were as in the Table. Conclusions: LCr is frequent in Japanese female pts. ddTC in practice setting seems safe, and hemTX of ddTC are similar with those observed in NOVEL trial. The rationale using a minimum value of 0.7 mg/dl should be further studied by larger population, such as pts in NOVEL trial. [Table: see text]

Oxaliplatin or Paclitaxel in Patients With Platinum-Pretreated Advanced Ovarian Cancer: A Randomized Phase II Study of the European Organization for Research and Treatment of Cancer Gynecology Group

2000 ◽  
Vol 18 (6) ◽  
pp. 1193-1202 ◽  
Author(s):  
Martine J. Piccart ◽  
John A. Green ◽  
Angel Jimenez Lacave ◽  
Nick Reed ◽  
Ignace Vergote ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Time To Progression ◽  
European Organization ◽  
Randomized Phase Ii ◽  
Grade 3

PURPOSE: This was a multicentric, open, randomized, phase II study of single-agent paclitaxel and oxaliplatin to evaluate the efficacy of oxaliplatin in a relapsing progressive ovarian cancer patient population and to analyze the safety profile and impact of both agents on quality of life, time to progression, and survival. PATIENTS AND METHODS: Eighty-six patients with platinum-pretreated advanced ovarian cancer were randomly assigned to two arms: 41 received paclitaxel at 175 mg/m2 over 3 hours every 3 weeks, and 45 received oxaliplatin at 130 mg/m2 over 2 hours every 3 weeks. For inclusion, patients had to have a performance status of 0 to 2 and to have received at least one and no more than two prior cisplatin- and/or carboplatin-containing chemotherapy regimens within the last 12 months. RESULTS: Seven confirmed responses were observed in each arm, for an overall response rate in the total treated population of 17% (95% confidence interval [CI], 7% to 32%) in the paclitaxel arm and 16% (95% CI, 7% to 29%) in the oxaliplatin arm. Median time to progression was 14 weeks and 12 weeks, and overall survival was 37 weeks and 42 weeks in the paclitaxel and oxaliplatin arms, respectively. Among 63 patients with a 0- to 6-month progression-free, platinum-free interval, there were five objective responses with paclitaxel in 31 patients and two objective responses with oxaliplatin in 32 patients. Nine patients (22%) in the paclitaxel arm had grade 3 or 4 neutropenia (National Cancer Institute of Canada [NCIC] Common Toxicity Criteria). Two patients (4%) experienced grade 3 thrombocytopenia in the oxaliplatin arm. Maximum grade (grade 3) NCIC neurosensory toxicity was experienced by three patients (7%) in the paclitaxel arm and by four patients (9%) in the oxaliplatin arm. CONCLUSION: Single-agent oxaliplatin at 130 mg/m2 every 3 weeks is active with moderate toxicity in patients with cisplatin-/carboplatin-pretreated advanced ovarian cancer.

Topotecan Compared With No Therapy After Response to Surgery and Carboplatin/Paclitaxel in Patients With Ovarian Cancer: Multicenter Italian Trials in Ovarian Cancer (MITO-1) Randomized Study

2004 ◽  
Vol 22 (13) ◽  
pp. 2635-2642 ◽  
Author(s):  
Sabino De Placido ◽  
Giovanni Scambia ◽  
Giovanni Di Vagno ◽  
Emanuele Naglieri ◽  
Alessandra Vernaglia Lombardi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Residual Disease ◽  
Randomized Study ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Significant Difference ◽  
Grade 3

Purpose Topotecan is an active second-line treatment for advanced ovarian cancer. Its efficacy as consolidation treatment after first-line standard chemotherapy is unknown. Patients and Methods To investigate whether topotecan (1.5 mg/m2 on days 1 through 5, four cycles, every 3 weeks) prolonged progression-free survival (PFS) for patients responding to standard carboplatin (area under the curve 5) and paclitaxel (175 mg/m2 administered as a 3-hour infusion in six cycles; CP), a multicenter phase III study was performed with an 80% power to detect a 50% prolongation of median PFS. Patients were registered at diagnosis and randomized after the end of CP. Results Two hundred seventy-three patients were randomly assigned (topotecan, n = 137; observation, n = 136), with a median age of 56 years. Stage at diagnosis was advanced in three fourths of patients (stage III in 65% of patients; stage IV in 10%); after primary surgery, 46% had no residual disease and 20% were optimally debulked. After CP, 87% reached a clinical complete response, and 13% achieved a partial response. Neutropenia (grade 3/4 in 58% of the patients) and thrombocytopenia (grade 3 in 21%; grade 4 in 3%) were the most frequent toxicities attributed to topotecan. There was no statistically significant difference in PFS between the arms (P = .83; log-rank test): median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm. Hazard ratio of progression for patients receiving topotecan was 1.18 (95% CI, 0.86 to 1.63) after adjustment for residual disease, interval debulking surgery, and response to CP. Conclusion The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel.

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