Recombinant human interleukin-3 to dose-intensify carboplatin and cyclophosphamide chemotherapy in epithelial ovarian cancer: a phase I trial.

1995 ◽  
Vol 13 (3) ◽  
pp. 733-740 ◽  
Author(s):  
G J Veldhuis ◽  
P H Willemse ◽  
M M van Gameren ◽  
J G Aalders ◽  
N H Mulder ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Optimal Dose ◽  
Interleukin 3 ◽  
Nonsignificant Difference ◽  
Facial Edema ◽  
Diffuse Erythema ◽  
The Mean ◽  
Advanced Epithelial Ovarian Cancer ◽  
Carboplatin Dose

PURPOSE To define the optimal dose of recombinant human interleukin-3 (rhIL-3) required to intensify the dose of carboplatin and cyclophosphamide for advanced epithelial ovarian cancer. PATIENTS AND METHODS Seventeen patients were treated on day 1 with carboplatin (dose adjusted for creatinine clearance: range, 257 to 385 mg/m2; median, 300 mg/m2) and cyclophosphamide (750 mg/m2). rhIL-3 5 micrograms/kg/d (n = 10) or 10 micrograms/kg/d (n = 7) was administered subcutaneously (SC) on days 2 through 11. Carboplatin dose was escalated if no postponement of cycles 1 to 3 had occurred. RESULTS A 3-week interval was achieved in 62% of cycles and a 4-week interval in 81%, with no difference between the rhIL-3 doses. A neutrophil nadir less than 0.5 x 10(9)/L occurred in 35% of the cycles at 5 micrograms/kg/d and in 52% at 10 micrograms/kg/d of rhIL-3 (nonsignificant difference). The mean platelet nadir in cycle 1 was 173 +/- 78 x 10(9)/L at 5 micrograms/kg/d and 340 +/- 152 x 10(9)/L at 10 micrograms/kg/d of rhIL-3 (P < .05), with a faster recovery of platelets at 10 micrograms/kg/d (P < .05). Progressive myelotoxicity occurred for leukocytes and platelets at both rhIL-3 doses and required chemotherapy postponement in later cycles. The planned six cycles were completed by 41% of patients. Fever (> or = 38.5 degrees C) occurred in 38% of cycles at 5 micrograms/kg/d and in 97% at 10 micrograms/kg/d (P < .0005); headache and myalgias occurred in 30% and 44%, respectively. After two cycles, diffuse erythema, facial edema, and urticaria were observed in two patients at 5 micrograms/kg/d and in five patients at 10 micrograms/kg/d of rhIL-3. This resolved after discontinuation of rhIL-3 and administration of corticosteroids and antihistamines. CONCLUSION A dose of 5 micrograms/kg/d of rhIL-3 proved to be optimal to intensify the carboplatin and cyclophosphamide regimen. It permitted the administration of carboplatin and cyclophosphamide combination therapy every 3 weeks in 62% of cycles.

CA125 levels are a weak predictor of optimal cytoreductive surgery in patients with advanced epithelial ovarian cancer

2003 ◽  
Vol 13 (2) ◽  
pp. 120-124 ◽  
Author(s):  
S. Memarzadeh ◽  
S. B. Lee ◽  
J. S. Berek ◽  
R. Farias-Eisner
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cytoreductive Surgery ◽  
Predictive Value ◽  
Maximal Dimension ◽  
Optimal Cytoreduction ◽  
Cut Point ◽  
Ca125 Level ◽  
The Mean ◽  
Advanced Epithelial Ovarian Cancer

The utility of preoperative CA125 to predict optimal primary tumor cytoreduction in patients with advanced (stages IIIC and IV) epithelial ovarian cancer is controversial. In this paper, we retrospectively review patients with stage IIIC and IV epithelial ovarian cancer who underwent primary cytoreductive surgery from 1989 to 2001. Ninety-nine patients were identified and included in the analysis. All patients had preoperative CA125 levels measured. Operative and pathology reports were reviewed. Optimal cytoreduction was defined as largest volume of residual disease < 1 cm in maximal dimension. Mean values were compared with t-test on a log scale when needed. The optimal cut-point for discriminating between those with vs. without optimal cytoreduction was determined using the receiver operator curve (ROC) method. Optimal cytoreduction was achieved in 73% of patients. Among patients with optimal cytoreductive status the mean CA125 level was 569, while among patients with suboptimal cytoreduction the mean CA125 level was 1520 (P < 0.007). A CA125 level of 912 was identified as the optimal cut-point to distinguish the two groups. Using this CA125 level, the sensitivity of this test in predicting optimal cytoreduction was 58% and the specificity was 54%. The positive predictive value of CA125 for optimal cytoreduction was 78% and the negative predictive value was 31%. We conclude that CA125 level is a weak positive and negative predictor of optimal cytoreductive surgery in patients with advanced epithelial ovarian cancer. The CA125 level should not be used as a primary predictor of the outcome of cytoreductive surgery and should be viewed in the context of all other preoperative features.

A clinical study of tremelimumab alone or in combination with olaparib in patients with advanced epithelial ovarian cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6045-6045
Author(s):  
Stephanie Gaillard ◽  
Maureen Berg ◽  
Jeanne Harrison ◽  
Peng Huang ◽  
James M. Leatherman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Epithelial Ovarian Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Optimal Dose ◽  
Clinical Activity ◽  
Immune Mediated ◽  
Advanced Epithelial Ovarian Cancer ◽  
Dose Levels

6045 Background: Single agent immunotherapy (IO) has shown only modest clinical activity for the treatment of ovarian cancer. The combination of anti-programmed death-1 and PARP inhibitors showed promising activity in early trials. Here, we report the results of an open-label, parallel arm, dose escalation study of tremelimumab (T) alone or in combination with olaparib (O) in patients (pts) with advanced epithelial ovarian cancer (EOC). Methods: Pts with recurrent/persistent EOC who had progression < 12 months from last platinum exposure were enrolled. Prior therapy with IO (except anti-CTLA-4) or PARP inhibitor was allowed. Pts were randomized to either T 10mg/kg every 4 weeks (wks) x 7 then every 12 wks (Arm A) or T with O twice daily at three planned dose levels (Arm B). The primary objectives were safety, pharmacodynamic (PD) change in CD4+ICOShi peripheral T cells by flow cytometry, and identification of the optimal dose combination of T with O. Secondary objectives included 6-month progression-free survival (PFS6) and objective response rate (ORR). Results: A total of 24 pts were treated, 12 on Arm A, and 12 on two Arm B dose levels. Pts had a median age of 60 years (range 44-81). Histologic subtypes included high-grade serous EOC (20 pts, 83%), clear cell (3 pts, 13%), and moderately-differentiated adenocarcinoma (1 pt, 4%). BRCA1 mutation (mt) was present in 2 cases, BRCA2 mt in 1. Median number of prior regimens was 3.5 (range 1-9). Most adverse events (AEs) were attributable to T, the most common grade 3 toxicities were rash (13%), immune-mediated hepatitis (8%), and colitis (8%). No grade ≥4 toxicities were identified. Immune-mediated AEs also included acute kidney injury, hypophysitis, and hypothyroidism. No dose limiting toxicities were identified on Arm B. Two pts in Arm B had >PFS6. Of 20 pts evaluable for response, there was 1 partial response (Arm B), and 9 pts had stable disease (6 on Arm A, 3 on Arm B). Mean percentage of CD4+ICOShi T cells was significantly increased on Days 15 and 22 compared to Day 1 at both T dose levels (Table).T at 3 mg/kg with O at 150mg is the optimal dose of those tested. Conclusions: T and T with O was tolerable, with modest clinical activity in this pt population. AEs were as expected, and peripheral CD4+ICOShi T cells increased on therapy. Clinical trial information: 02485990. [Table: see text]

scholarly journals A prospective study evaluating preoperative (clinical, imaging) and intraoperative predictors of suboptimal debulking in advanced epithelial ovarian cancer

2016 ◽  
Author(s):  
Anupama Rajanbabu ◽  
Kiran Bagul ◽  
Keyword(s):  
Ovarian Cancer ◽  
Small Bowel ◽  
Ct Scan ◽  
Epithelial Ovarian Cancer ◽  
Survival Benefit ◽  
Demographic Data ◽  
Univariate Analysis ◽  
Imaging Results ◽  
Advanced Epithelial Ovarian Cancer ◽  
Optimal Debulking

Introduction: In advanced epithelial ovarian cancer, there is a survival benefit for patients who achieve optimalcytoreduction. Suboptimallycytoreduced patients are at risk of the increased morbidity of a surgery without associated survival benefit. Predicting which patients can undergo optimal cytoreduction represents a critical decision-making point. Present study analyses the predictors, pre operative (clinical and radiologic) and intraoperative of suboptimal debulking. Methods: This was a prospective observational study conducted at Amrita Institute of Medical Sciences from March 2013 to May 2015. All the patients with clinically (physical examination, laboratory and imaging results) diagnosed Stage IIIc epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (PPC) who were planed for primary debulking surgery were included. The demographic data and details of tumor markers, radiological investigations including CT scan, intra operative findings and histopathologic details were collected. Statistical analysis was done using SPSS v20.0. Results: 36 patients fit the inclusion criteria. Gross ascites wasthe clinical parameter found to be associated with suboptimal debulking. CT scan had low sensitivity (35-53%) in diagnosing small bowel mesenteric and porta hepatis disease and high sensitivity in diagnosing diffuse peritoneal thickening, omental disease, diaphragmatic and nodal disease. On univariate analysis diffuse peritoneal thickening and small bowel serosa and mesenteric disease were significantly consistent with sub optimal debulking. Conclusion: Finding out disease at the sites which are associated with suboptimal debulking (diffuse peritoneal thickening, smallbowel mesenteric and serosal disease) pre operatively or at the beginning of surgery can predict optimal debulking and can help avoid un necessary surgery.

scholarly journals Clinical Impact of Lymphadenectomy after Neoadjuvant Chemotherapy in Advanced Epithelial Ovarian Cancer: A Review of Available Data

2021 ◽  
Vol 10 (2) ◽  
pp. 334
Author(s):  
Stephanie Seidler ◽  
Meriem Koual ◽  
Guillaume Achen ◽  
Enrica Bentivegna ◽  
Laure Fournier ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Node ◽  
Neoadjuvant Chemotherapy ◽  
Epithelial Ovarian Cancer ◽  
Lymph Node Dissection ◽  
Prospective Trial ◽  
Node Dissection ◽  
Advanced Epithelial Ovarian Cancer ◽  
The Impact ◽  
Systematic Lymph Node Dissection

Recent robust data allow for omitting lymph node dissection for patients with advanced epithelial ovarian cancer (EOC) and without any suspicion of lymph node metastases, without compromising recurrence-free survival (RFS), nor overall survival (OS), in the setting of primary surgical treatment. Evidence supporting the same postulate for patients undergoing complete cytoreductive surgery after neoadjuvant chemotherapy (NACT) is lacking. Throughout a systematic literature review, the aim of our study was to evaluate the impact of lymph node dissection in patients undergoing surgery for advanced-stage EOC after NACT. A total of 1094 patients, included in six retrospective series, underwent either systematic, selective or no lymph node dissection. Only one study reveals a positive effect of lymphadenectomy on OS, and two on RFS. The four remaining series fail to demonstrate any beneficial effect on survival, neither for RFS nor OS. All of them highlight the higher peri- and post-operative complication rate associated with systematic lymph node dissection. Despite heterogeneity in the design of the studies included, there seems to be a trend showing no improvement on OS for systematic lymph node dissection in node negative patients. A well-conducted prospective trial is mandatory to evaluate this matter.

scholarly journals Perioperative fluid balance and major postoperative complications in surgery for advanced epithelial ovarian cancer

2021 ◽  
Vol 161 (2) ◽  
pp. 402-407
Author(s):  
Emma Hasselgren ◽  
Daniel Hertzberg ◽  
Tina Camderman ◽  
Håkan Björne ◽  
Sahar Salehi
Keyword(s):  
Ovarian Cancer ◽  
Postoperative Complications ◽  
Epithelial Ovarian Cancer ◽  
Fluid Balance ◽  
Advanced Epithelial Ovarian Cancer

scholarly journals E-Cadherin fragments as potential mediators for peritoneal metastasis in advanced epithelial ovarian cancer

2016 ◽  
Vol 114 (2) ◽  
pp. 213-220 ◽  
Author(s):  
Fabian Trillsch ◽  
Sascha Kuerti ◽  
Christine Eulenburg ◽  
Eike Burandt ◽  
Linn Woelber ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Peritoneal Metastasis ◽  
Advanced Epithelial Ovarian Cancer ◽  
E Cadherin
Sign in / Sign up

Export Citation Format

Share Document