Comparative phase II study of intraperitoneal (IP) versus intravenous (IV) carboplatin administration with IV paclitaxel in patients with bulky residual disease after primary debulking surgery for epithelial ovarian or primary peritoneal cancer: A Sankai Gynecology Study Group (SGSG) study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5584-5584
Author(s):  
K. Fujiwara ◽  
S. Nagao ◽  
J. Kigawa ◽  
J. Noma ◽  
N. Akamatsu ◽  
...  
Keyword(s):  
Phase Ii ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Median Number ◽  
Phase Iii ◽  
Debulking Surgery ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Primary Debulking Surgery ◽  
Initial Surgery

5584 Background: To assess the anti-tumor effect and safety of IP carboplatin (C) administration comparing with IV C administration in combination with IV infusion of paclitaxel (P). Methods: This is a non-randomized comparative phase II trial. Eligible patients were those with histologically confirmed epithelial ovarian or primary peritoneal cancer who received initial surgery and ended up with residual disease >= 2 cm. They must have reasonable hematological, hepatic, renal function before receiving chemotherapy. The patients received either of the following treatment arms; IP Arm: IV P 175 mg/m2 over 3h followed by IP C AUC6, IV Arm: IV P 175 mg/m2 over 3h followed by IV C AUC6. The treatments were scheduled to repeat 6–8 cycles. Interval debulking surgery was allowed after 3 to 5 cycle of treatment. Each participating institution had to declare, before the study was opened, which of the treatment arms the patients from the institution would be entered. Primary endpoint was a response. Secondary endpoints were toxicity and progression-free survival (PFS) and overall survival (OS). Target accrual was 30 patients in each arm. Results: Total accrual was 26 patients for IP arm and 30 patients for IV arm between 2001 and 2005. The study was closed early, because of the conflict of protocols for IP treatment. Eligible patients were 24 in IP Arm and 25 for IV arm. Median number of treatment cycle was 6 for both arms. Although the difference was not statistically significant, response rate was better in the IP Arm. Response rates were 83.3% (95%CI: 62.6%-95.3%) for IP Arm and 60.0% (95%CI: 38.7%-78.9%) for IV Arm. As of median followup of 31 months, median PFS is 25 months for IP Arm and 21 months for IV Arm,. Median OS is not reached for IP Arm, and 52 months for IV arm. Incidences of hematological and non-hematological toxicities were essentially the same on both arms. Conclusions: IP administration of C may be a better treatment strategy for epithelial ovarian and primary peritoneal cancer patients. A randomized phase III trial including bulky residual disease for comparison of IP and IV carboplatin treatment. No significant financial relationships to disclose.

Use of ablation and ultrasonic aspiration at primary debulking surgery in advanced stage ovarian, fallopian tube, and primary peritoneal cancer

2020 ◽  
Vol 30 (7) ◽  
pp. 1052-1057
Author(s):  
Sue Li ◽  
Beryl Manning-Geist ◽  
Allison Gockley ◽  
Amanda Ramos ◽  
Rachel C. Sisodia ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Fallopian Tube ◽  
Residual Disease ◽  
Surgical Techniques ◽  
Progression Free Survival ◽  
Debulking Surgery ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Primary Debulking Surgery ◽  
Complete Surgical Resection

ObjectivesOvarian cancer patients with miliary disease have the lowest rates of complete surgical resection and poorest survival. Adjunct surgical techniques may potentially increase rates of complete surgical resection. No studies have evaluated the use of these techniques in primary debulking surgery for ovarian cancer patients with miliary disease. The aim of this study was to examine the use of adjunct surgical techniques during primary debulking surgery for patients with advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer with miliary disease.MethodsMedical records of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IIIC–IVB epithelial ovarian, fallopian tube, or primary peritoneal cancer with miliary disease undergoing primary debulking surgery from January 2010 to December 2014 were reviewed. Adjunct surgical techniques were defined as ultrasonic surgical aspiration, argon enhanced electrocautery, thermal plasma energy, and traditional electrocautery ablation. Patients undergoing surgery with and without these devices were compared with respect to demographics, operative characteristics, postoperative complications, residual disease, progression free survival and overall survival.ResultsA total of 135 patients with miliary disease underwent primary debulking surgery, of which 30 (22.2%) patients used adjunct surgical techniques. The most common devices were ultrasonic surgical aspiration (40%) and argon enhanced electrocautery (36.7%). The most common sites of use were diaphragm (63.3%), pelvic peritoneum (30%), bowel mesentery (20%), and large bowel serosa (20%). There were no differences in age, stage, primary site, histology, operative time, surgical complexity, or postoperative complications for patients operated on with or without these devices. Volume of residual disease was similar (0.1–1 cm: 60% with adjunct techniques versus 68.6% without; complete surgical resection: 16.7% with adjunct techniques versus 13.3% without; p=0.67). For patients with ≤1 cm residual disease, median progression free survival (15 versus 15 months, p=0.65) and median overall survival (40 versus 55 months, p=0.38) were also similar.ConclusionAdjunct surgical techniques may be incorporated during primary debulking surgery for patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with miliary disease; however, these do not improve the rate of optimal cytoreduction.

A phase II clinical trial of metformin as a cancer stem cell targeting agent in stage IIc/III/IV ovarian, fallopian tube, and primary peritoneal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5556-5556 ◽  
Author(s):  
Ronald J. Buckanovich ◽  
Jason Brown ◽  
Jessica Shank ◽  
Kent A. Griffith ◽  
R. Kevin Reynolds ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Antitumor Effects ◽  
Peritoneal Cancer ◽  
Primary Debulking Surgery ◽  
Primary Endpoints ◽  
Increased Sensitivity

5556 Background: Epidemiologic and preclinical studies suggest that Metformin has antitumor effects which may be due to an impact on cancer stem-like cells (CSC). We present a phase II trial of metformin administered in combination with chemotherapy for patients with advanced stage epithelial ovarian cancer (EOC). Primary endpoints were 18 month progression free survival (PFS) and CSC number in Metformin treated tumors. Methods: Thirty-eight patients with confirmed stage IIC(n=1)/III(n=25)/IV(n=12) EOC were treated with either neoadjuvant metformin followed primary debulking surgery and adjuvant Metformin+chemotherapy, or neo-adjuvant metformin+chemotherapy, followed by interval debulking and adjuvant chemotherapy+Metformin. Patients were evaluated for side effects, PFS and overall survival (OS). Metformin treated tumors were evaluated for the presence of CSC via FACS and sphere assays. Results: Thirty-two patients (84%) completed at least six cycles of metformin+chemotherapy. Metformin was well tolerated with only one grade III/IV treatment-related adverse event (3%) noted. Common adverse effects were diarrhea (18%) and nausea (16%). Eighteen month PFS was 65.4% (95% confidence interval 47.9-78.3), Median PFS was 21.7 months (CI-17-26.7). Estimated three year OS was 73.5% (CI-54.7-84.3) with median OS not reached after a media follow-up of 33 months. Finally, tumors treated with metformin were noted to have a 3-fold decrease in ALDH+ CSC at baseline, increased sensitivity to Cisplatin in vitro, and a reduced ability to amplify ALDH+ CSC with passage in vitro. Conclusions: This is the first prospective study of Metformin in EOC patients. Translational studies confirm an impact of metformin on CSC. Metformin was well tolerated and outcome results were favorable, supporting the use of Metformin in phase-III studies. Clinical trial information: NCT01579812.

scholarly journals Aggressive surgery could overcome the extent of initial peritoneal dissemination for advanced ovarian, fallopian tube, and peritoneal carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kyoko Nishikimi ◽  
Shinichi Tate ◽  
Ayumu Matsuoka ◽  
Makio Shozu
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Fallopian Tube ◽  
Peritoneal Dissemination ◽  
Residual Disease ◽  
Peritoneal Cancer Index ◽  
Progression Free Survival ◽  
Peritoneal Carcinoma ◽  
Debulking Surgery ◽  
Peritoneal Cancer ◽  
Primary Debulking Surgery

AbstractWe examined whether the extent of initial peritoneal dissemination affected the prognosis of patients with advanced ovarian, fallopian tube, and peritoneal carcinoma when initially disseminated lesions > 1 cm in diameter were removed, regardless of the timing of aggressive cytoreductive surgery. The extent of peritoneal dissemination was assessed by the peritoneal cancer index (PCI) at initial laparotomy in 186 consecutive patients with stage IIIC/IV. Sixty patients underwent primary debulking surgery and 109 patients underwent neoadjuvant chemotherapy followed by interval debulking surgery. Seventeen patients could not undergo debulking surgery because of disease progression during neoadjuvant chemotherapy. The median initial PCI were 17. Upper abdominal surgery and bowel resection were performed in 149 (80%) and 171 patients (92%), respectively. Residual disease ≤ 1 cm after surgery was achieved in 164 patients (89%). The initial PCI was not significantly associated with progression-free survival (PFS; p = 0.13) and overall survival (OS; p = 0.09). No residual disease and a high-complexity surgery significantly prolonged PFS (p < 0.01 and p = 0.02, respectively) and OS (p < 0.01 and p ≤ 0.01, respectively). The extent of initial peritoneal dissemination did not affect the prognosis when initially disseminated lesions > 1 cm were resected.

scholarly journals Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850)

2020 ◽  
Vol 30 (11) ◽  
pp. 1657-1664 ◽  
Author(s):  
Anna Fagotti ◽  
Maria Gabriella Ferrandina ◽  
Giuseppe Vizzielli ◽  
Tina Pasciuto ◽  
Francesco Fanfani ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Progression Free Survival ◽  
Debulking Surgery ◽  
Free Survival ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Primary Debulking Surgery ◽  
Interval Debulking Surgery ◽  
Tumor Load

ObjectiveTo investigate whether neoadjuvant chemotherapy followed by interval debulking surgery is superior to primary debulking surgery in terms of perioperative complications and progression-free survival, in advanced epithelial ovarian, fallopian tube or primary peritoneal cancer patients with high tumor load.MethodsPatients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer (stage IIIC-IV) underwent laparoscopy. Patients with high tumor load assessed by a standardized laparoscopic predictive index were randomly assigned (1:1 ratio) to undergo either primary debulking surgery followed by adjuvant chemotherapy (arm A), or neoadjuvant chemotherapy followed by interval debulking surgery and adjuvant chemotherapy (arm B). Co-primary outcome measures were progression-free survival and post-operative complications; secondary outcomes were overall survival, and quality of life. Survival analyses were performed on an intention-to-treat population.Results171 patients were randomly assigned to primary debulking surgery (n=84) versus neoadjuvant chemotherapy (n=87). Rates of complete resection (R0) were different between the arms (47.6% in arm A vs 77.0% in arm B; p=0.001). 53 major postoperative complications were registered, mainly distributed in arm A compared with arm B (25.9% vs 7.6%; p=0.0001). All patients were included in the intent-to-treat analysis. With an overall median follow-up of 59 months (95% CI 53 to 64), 142 (83.0%) disease progressions/recurrences and 103 deaths (60.2%) occurred. Median progression-free and overall survival were 15 and 41 months for patients assigned to primary debulking surgery, compared with 14 and 43 months for patients assigned to neoadjuvant chemotherapy, respectively (HR 1.05, 95% CI 0.77 to 1.44, p=0.73; HR 1.12, 95% CI 0.76 to 1.65, p=0.56).ConclusionsNeoadjuvant chemotherapy and primary debulking surgery have the same efficacy when used at their maximal possibilities, but the toxicity profile is different.

A retrospective analysis of lymph node status in advanced ovarian, fallopian, and peritoneal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17074-e17074
Author(s):  
Yoshio Itani ◽  
Sayuri Morita ◽  
Hitomi Sugimoto ◽  
Yoshiki Takeda ◽  
Yoshikazu Sasaki ◽  
...  
Keyword(s):  
Lymph Node ◽  
Statistical Significance ◽  
Figo Stage ◽  
Median Number ◽  
T Test ◽  
Lymph Node Status ◽  
Debulking Surgery ◽  
Peritoneal Cancer ◽  
Primary Debulking Surgery ◽  
Interval Debulking Surgery

e17074 Background: The purpose of this study was to assess lymph node (LN) status; greatest dimension (D), D of metastatic LN (LN (+)) foci (MF), number of LN (+) of each patient, and MF area aggregated in each patient affected by LN metastasis in FIGO stage III and IV ovarian, fallopian, and peritoneal cancer. Methods: We researched the consecutive 25 patients who underwent primary debulking surgery or neoadjuvant chemotherapy (NAC) followed by interval debulking surgery including systemic lymphadenectomy from 2004 to 2015. Non-serous histology was 20 % (5/25). LN (+) were detected in 12.6% (169/1344) of lymph node preparations. Results: The patients’ median age was 53 years. Median number of LN (+) and sum of MF area in each patient were 2 (range 0-37) and 2 mm2 (range 0- 498). Mean D of the entire LN and of the MF were 4.7mm (95%Confidence Interval (CI); 4.5,4.9) and 6.1mm(95% CI; 5.2, 7.0). The LN (+) displayed a significantly larger mean D value (7.9 mm, 95% CI: 7.4, 8.5) than the non-metastatic lymph nodes (LN (-)) (4.2 mm, 95% CI: 4.0, 4.4) (p<0.05; student t test). D of MF (mm) was approximated by LN (+) area (mm2) as follows; (D of MF) = 2.58+ 0.094*(LN (+) area)+ 0.062* ( ( LN (+) area)-43.2)2; R2=0.75; p<0.0001. The D of MF with NAC, 5.0 mm (95%CI: 3.6, 6.4) demonstrated smaller than that without NAC, 7.0 mm (95%CI: 5.8, 8.1) (p<0.05; student t test). The proportion of LN (-) patients was significantly higher in the NAC group (44%, 4/9) than in the non-NAC group (6%, 1/16) (p=0.022). D of LN (+), D of MF ≥10 mm, sum of MF area, and number of LN (+) ≥ 2 did not achieve statistical significance in analysis with the relative risk (RR) of death. Conclusions: LN (+) exhibits larger D than LN (-) and D of MF could be estimated by LN (+) area. Some MFs shrink after NAC, and hence, become difficult to detect pathologically. In advanced ovarian, fallopian, and peritoneal cancer LN size and sum of MF area could not show an impact on prognosis.

Randomized, Open-Label, Phase III Study Comparing Patupilone (EPO906) With Pegylated Liposomal Doxorubicin in Platinum-Refractory or -Resistant Patients With Recurrent Epithelial Ovarian, Primary Fallopian Tube, or Primary Peritoneal Cancer

2012 ◽  
Vol 30 (31) ◽  
pp. 3841-3847 ◽  
Author(s):  
Nicoletta Colombo ◽  
Elzbieta Kutarska ◽  
Meletios Dimopoulos ◽  
Duk-Soo Bae ◽  
Izabella Rzepka-Gorska ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Open Label ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Significant Difference ◽  
Platinum Refractory

Purpose This study compared the efficacy and safety of patupilone with those of pegylated liposomal doxorubicin (PLD) in patients with platinum-refractory or -resistant epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. Patients and Methods Patients with three or fewer prior regimens were eligible if they had received first-line taxane/platinum-based combination chemotherapy and were platinum refractory or resistant. Patients were randomly assigned to receive patupilone (10 mg/m2 intravenously every 3 weeks) or PLD (50 mg/m2 intravenously every 4 weeks). Results A total of 829 patients were randomly assigned (patupilone, n = 412; PLD, n = 417). There was no statistically significant difference in overall survival (OS), the primary end point, between the patupilone and PLD arms (P = .195; hazard ratio, 0.93; 95% CI, 0.79 to 1.09), with median OS rates of 13.2 and 12.7 months, respectively. Median progression-free survival was 3.7 months for both arms. The overall response rate (all partial responses) was higher in the patupilone arm than in the PLD arm (15.5% v 7.9%; odds ratio, 2.11; 95% CI, 1.36 to 3.29), although disease control rates were similar (59.5% v 56.3%, respectively). Frequently observed adverse events (AEs) of any grade included diarrhea (85.3%) and peripheral neuropathy (39.3%) in the patupilone arm and mucositis/stomatitis (43%) and hand-foot syndrome (41.8%) in the PLD arm. Conclusion Patupilone did not demonstrate significant improvement in OS compared with the active control, PLD. No new or unexpected serious AEs were identified.

scholarly journals Advanced stage ovarian cancer patients with neoadjuvant chemotherapy suffered worse recurrence free survival

2020 ◽  
Author(s):  
Cailiang Wu ◽  
Xuexin Zhou ◽  
Yiwen Feng ◽  
Yi Miao ◽  
Ye Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Recurrence Free Survival ◽  
Advanced Stage ◽  
Debulking Surgery ◽  
Fallopian Tube Cancer ◽  
Free Survival ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Primary Debulking Surgery

Abstract Background Neoadjuvant chemotherapy (NACT) has been applied for the treatment of patients with advanced-stage epithelial ovarian cancer (EOC), fallopian tube cancer, and primary peritoneal cancer, as these patients have a low likelihood of achieving optimal debulking and are thus poor surgical candidates. Herein, we explore the effects of NACT and compare the surgical outcomes and recurrence data in patients who receive interval debulking surgery followed NACT(NACT-IDS) or primary debulking surgery(PDS). Methods A retrospective, single-center, observational study was conducted. Patients with advanced-stage EOC, fallopian tube cancer and primary peritoneal cancer who were treated with NACT or primary debulking surgery were enrolled. The effects of NACT as well as the surgical outcomes and recurrence data were compared between the NACT-IDS and PDS groups. Results The albumin level was elevated (42.61±3.46 g/L vs. 37.47±5.42 g/L, P=0.001) and the levels of CA12-5 and HE4 significantly decreased (P=0.002, 0.003) in patients after neoadjuvant courses. The operation time, amount of blood loss during surgery, rate of bowel resection, time to chemotherapy, and platinum-free interval were comparable between the two groups (P＞0.05). Recurrence-free survival was worse in the NACT-IDS group than in the PDS group (HR=2.406, 95% CI[1.024, 5.657]). Conclusion NACT improved the condition of advanced-stage patients, but a poor recurrence free survival rate was observed; thus, NACT should not be applied in non-selected patients.

Efficacy and safety of tivozanib in recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5538-5538 ◽  
Author(s):  
Wendy M Swetzig ◽  
John Robert Lurain ◽  
Emily Berry ◽  
Mario Javier Pineda ◽  
Shohreh Shahabi ◽  
...  
Keyword(s):  
Fallopian Tube ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Median Number ◽  
Vegf Receptor ◽  
Open Label ◽  
Fallopian Tube Cancer ◽  
Primary Peritoneal Cancer ◽  
Peritoneal Cancer ◽  
Platinum Resistant

5538 Background: Tivozanib is a potent, selective pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor with a long half-life. This study assessed its activity in patients with recurrent, platinum-resistant ovarian cancer (OC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC). Methods: This open-label phase II study used a Simon’s two-stage design. Eligible patients had recurrent, platinum-resistant OC, FTC or PPC; ECOG PS of 0-1; normal end organ function; and measurable or detectable disease. There was no limit on the number of prior regimens. Treatment consisted of tivozanib 1.5 mg orally once daily (3 weeks on/1 week off). The primary endpoint was response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity assessment. If 1 partial response (PR) was observed in stage I [n = 12], enrollment proceeded to stage II. The null hypothesis was rejected for ≥ 4 responses in 30 patients. Results: Thirty-one patients were enrolled, and 30 were treated. Twenty-three had OC [76.67%], 5 FTC [16.67%] and 2 PPC [6.67%]. Twenty-six had measurable [86.67%] and 4 detectable disease [13.37%]. The median age was 60, and median number of prior regimens was 4 [range 1-9]. Four PRs [13.33%] were recorded. Twelve patients had stable disease (SD) [40%]. The clinical benefit rate (PR + SD) was 53%. Seven patients [23.33%] survived progression-free for > 6 mos. One patient continued treatment for > 2 yrs. The median PFS was 4 mos [range 1-25] and median OS was 8 mos [range 1-39]. There were no treatment-related deaths. Grade 3-4 related toxicities were hypertension [8], fatigue [3], fistula [2], hyponatremia [2], intestinal perforation, obstruction, stroke, proteinuria, hypomagnesemia, hypoalbuminemia, portal hypertension, nausea and anemia [1 each]. Frequent grade 1-2 related toxicities included fatigue [19], hypertension [13], anorexia [12], arthralgia [11], diarrhea [11], weight loss [10], hoarseness [8], headache [8] and nausea [7]. Exploratory analyses in tumor samples are ongoing. Conclusions: Tivozanib is active in patients with recurrent OC, FTC or PPC, without substantial toxicity, supporting its further development. Clinical trial information: NCT01853644.

Intraperitoneal chemotherapy in the management of patients with advanced epithelial ovarian cancer: a critical review of the literature

2008 ◽  
Vol 18 (5) ◽  
pp. 943-953 ◽  
Author(s):  
A. Gadducci ◽  
P. F. Conte
Keyword(s):  
Ovarian Cancer ◽  
Decision Making ◽  
Residual Disease ◽  
Progression Free Survival ◽  
High Response Rate ◽  
Phase Iii ◽  
Small Subset ◽  
First Line ◽  
Initial Surgery ◽  
Systemic Treatments

The use of intraperitoneal (IP) chemotherapy has been advocated in different settings of patients with ovarian cancer. Cisplatin is the drug of choice because of its high response rate and minimal local toxicity. This treatment can be given to women with small residual disease after second look, with surgically assessed complete response rates of approximately 30%, and with a prolonged survival in small subset of patients. However, the use of IP chemotherapy as consolidation treatment of pathologically complete responders after first-line systemic chemotherapy has not been definitively evaluated in a phase III trial. There is much debate in the literature both for and against the use of IP chemotherapy in the first-line treatment of optimally debulked ovarian cancer patients. The recent Cochrane meta-analyses of eight randomized trials enrolling 1819 patients has shown that first-line IP chemotherapy improves progression-free survival and overall survival of patients with minimal residual disease after initial surgery. However, the potential for catheter-related complications, abdominal pain with infusion, and toxicities needs to be taken into consideration for decision making in each individual woman. Rectosigmoidal surgery can be associated with gross contamination of the operative field, and in this case, the catheter placement should not be performed during primary surgery but should be delayed to 3 weeks later. Patients should be provided with information on the survival and toxicity for both IP and systemic treatments, as well as practical information about the administration of each regimen, so that they may be involved in the decision-making process

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