Intraperitoneal therapy for ovarian cancer: Impact on survival and recurrence—The result of multi-institutional studies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16068-16068
Author(s):  
S. Takeuchi ◽  
H. Tsubamoto ◽  
S. Adachi ◽  
K. Ito ◽  
Y. Itani ◽  
...  

16068 Background: For optimal debulked mullerian cancer (MC), the Intraperitoneal (IP) therapy has become the effective modality of chemotherapy to obtain better prognosis. We have reported KCOG9811study: IP CDDP + Paclitaxel (PTX) intravenous (IV) 2 cycles followed by 3 cycles of usual PTX-Carboplatin (abstr.1970, ASCO2002). And we have also reported the feasibility study and satisfactory response rate of the weekly IP-PTX with IV Carboplatin therapy (IP-PIVC, abstr. 5120, ASCO2005). Objectives: We have conducted two types of IP therapy for optimal debulked MC to improve the progression free survival (PFS) and overall survival (OS). Here are the prognosis and recurrent fashion after these IP therapies. Methods: Twenty patients (pts) with optimal debulked ovarian cancer were enrolled for KCOG9811, and eleven pts with optimal debulked MC newly/recurrent diagnosed disease were enrolled for IP-PIVC. The regimen of each therapy consisted of as follows: KCOG9811:50mg/ m2 of CDDP was administered via IP port at operation, after 2 weeks (wks) of operation, PTX was administered at a dose of 175mg/ m2IV for 3hrs on day 1, CDDP was administered at 75mg/ m2IP on day 2, every 3wks for 2 cycles, followed by PTX 175mg/ m2 IV and Carboplatin AUC5 IV on day1 every 3wks for 3 cycles. The IP-PIVC therapy consisted of IP-PTX, on days 1, 8, 15 at a dose of 45 mg/m2 (3pts) and 60 mg/m2(8pts). Carboplatin was administered monthly at a dose of AUC 5 on day 1 only. 2–6 cycles were performed. Results: The mean observation time was 72.6 months (m) and 32.6m for KCOG9811 and IP-PIVC, respectively. As for the median PFS was 1308+ days and 678+ days, and the median OS was 2180+ days and 978+ days, respectively. The five years survival rate showed 59.3% on KCOG9811, and the three years survival rate showed 75.8% on IP-PIVC. As for recurrent fashion, liver metastases and proximal lymphnodes metastases, and retroperitoneal metastases were detected. Few cases recurred Intraperitoneal lesion with small ascites Conclusions: There are some differences in the recurrent fashion of IP treatment from that of IV treatment. IP treatment prevented ascitic recurrence. Further improvement of chemotherapy is necessary for liver metastasis and proximal lymphnodes. [Table: see text]

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2010-2010
Author(s):  
Eric Yamga ◽  
Richard Leblanc ◽  
Jean-Samuel Boudreault

Abstract Background: Multiple myeloma (MM) is the second most common hematologic cancer. The management of this disease consists of induction therapy followed by autologous hematopoietic stem cell transplantation (HCT). There is no standard of care as for the best induction regime. Recently, the first phase III study (Moreau P and all.) comparing two chemotherapy triplets in transplant-eligible patients, suggested a superiority of VTD over VCD. Although VTD was associated with better treatment response rates, the survival data remains to be seen. We wanted to retrospectively compare 3 Bortezomib-based therapies using response rates (RR), progression-free survival (PFS) and overall survival (OS). Bortezomib-Cyclophosphamide-Dexamethasone (CyBorD) remains the standard in Canada. Method: A total of 75 patients induced between 2010 and 2016 were analyzed. Their charts were reviewed and the data was retrospectively collected. Three distinct treatment groups were included : Vd (19), CyBorD (39) and VTD (17).The main outcome was treatment response rate, 2-year progression-free survival rate (PFS) and 2-year overall survival rate (OS). The secondary outcome was median PFS. Results: Patient characteristics are presented below (table 1). The difference between the treatment response rates were non-statistically significant but demonstrated a favorable trend towards VTD as the VGPR rate was 58.8%, 65% and 88.1% respectively in the Vd, CyBoRD and VTD groups (table 2 and 3). Median progression-free survival was significantly longer in the group that received VTD than in the group that received CyBord (3.58 years vs. 2,80 years; P = 0.03). The 2-year overall survival rate was 88,9%, 96,3% et 93,3% respectively in the 3 groups (table 4). Conclusion: The data from this retrospective study supports the superiority of the VTD induction regimen compared with CyBorD and Vd in terms of response rate and progression-free survival. However, there is no major difference in overall survival over the time period observed. Disclosures Leblanc: Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Inc.: Membership on an entity's Board of Directors or advisory committees. Boudreault:Celgen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252665
Author(s):  
Christine S. Walsh ◽  
Mitchell Kamrava ◽  
Andre Rogatko ◽  
Sungjin Kim ◽  
Andrew Li ◽  
...  

Objective To evaluate the combination of pembrolizumab, cisplatin and gemcitabine in recurrent platinum-resistant ovarian cancer. Methods Patients received six cycles of chemotherapy with gemcitabine and cisplatin on day 1 and day 8 of a 21-day treatment cycle. Pembrolizumab was administered on day 1 of cycles 3–6 and as maintenance monotherapy in cycles 7–34. Palliative radiation to a non-target symptomatic lesion was allowed. The primary objective was overall response rate by RECIST 1.1 criteria. Secondary objectives included safety, progression-free survival, time to progression, duration of response and overall survival. Results An interim analysis for futility was performed at 18 evaluable patients. Overall response rate was 60%, duration of response was 4.9 months and time to progression was 5.2 months. Progression-free survival at 6 and 12 months was 43% and 5%. Median progression-free survival was 6.2 months and median overall survival was 11.3 months. In all patients, CA125 levels reflected response and progression. There were no pseudoprogression events. After receiving palliative radiation during pembrolizumab maintenance, a patient with recurrent ovarian clear cell carcinoma had an exceptional and durable response that is ongoing for greater than 2 years. After consultation with the sponsor, based on the modest duration of response observed at the interim analysis for futility, the decision was made to close the trial to further accrual. Conclusions The addition of pembrolizumab to cisplatin and gemcitabine did not appear to provide benefit beyond chemotherapy alone in patients with recurrent platinum-resistant ovarian cancer.


2020 ◽  
Vol 9 (18) ◽  
pp. 1285-1292
Author(s):  
Shengqi He ◽  
Dongqing Hu ◽  
Haixia Feng ◽  
Ye Xue ◽  
Jin Jin ◽  
...  

Aim: PD-1 inhibitors have a leading role among immunotherapy while its efficacy on colorectal cancer (CRC) patients did not reach consensus and the small sample size remains as a limitation. Therefore, we undertook a meta-analysis on the effects of the monotherapy anti-PD-1 inhibitors in treating metastatic colorectal cancer (mCRC). Materials & methods: We searched databases to identify studies on efficacy of anti-PD-1 inhibitor on CRC. Objectives were objective response rate, progression-free survival rate, disease control rate and overall survival rate with their 95% CI. Results: The overall survival rate at 1-year was 64.2% (95% CI: 0.46–0.83). Disease control rate was 56.5% (CI: 0.27–0.86) and the objective response rate as 19.7% (CI: 0.08–0.32). The 1-year-progression-free survival rate was 38.4% (CI: 0.12–0.66). Sensitivity analysis and subgroup analysis were also conducted. Conclusion: The monotherapy anti-PD-1 inhibitors are effective in treating mCRC and could be a new option for dMMR mCRC patient in first-line treatment.


2021 ◽  
pp. ijgc-2020-002343
Author(s):  
Sabrina Chiara Cecere ◽  
Lucia Musacchio ◽  
Michele Bartoletti ◽  
Vanda Salutari ◽  
Laura Arenare ◽  
...  

IntroductionThe role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer.MethodsThis retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed.ResultsAmong 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively.ConclusionCytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval.


2020 ◽  
Vol 26 (7) ◽  
pp. 1566-1574 ◽  
Author(s):  
Madison Murphy ◽  
Grace Martin ◽  
Zahra Mahmoudjafari ◽  
Cory Bivona ◽  
Dennis Grauer ◽  
...  

Introduction Patients diagnosed with stage III ovarian cancer are at high risk of recurrence and optimal adjuvant therapy is often debated. There is limited literature that directly compares intraperitoneal paclitaxel and cisplatin with dose-dense paclitaxel and carboplatin. Objectives The primary objective was to compare progression-free survival, overall survival, and tolerability of adjuvant intraperitoneal paclitaxel and cisplatin to dose-dense paclitaxel and carboplatin in stage III ovarian cancer patients. Methods A retrospective, IRB-approved, single center chart review was conducted reviewing adult patients with stage III ovarian cancer undergoing adjuvant intraperitoneal therapy or dose-dense therapy between 2010 and 2018. Results Eighty-two patients were included in the final analysis; 44 in the intraperitoneal group and 38 in the dose-dense group. Intraperitoneal therapy was not associated with a longer progression-free survival (35.4 vs. 31.1 months; P = 0.97). The duration of overall survival did not differ between intraperitoneal and dose-dense (56.3 vs. 54.5 months; P = 0.55). Dose reductions were less frequent with intraperitoneal than dose-dense (11.36% vs. 31.58%; P = 0.02). No difference in treatment delays (45.5% vs. 65.8%; P = 0.07), dose cancellations (59.1% vs. 57.9%; P = 0.91), supportive care additions (95.5% vs. 84.2%; P = 0.09), or therapy discontinuation (59.1% vs. 39.5%; P = 0.07) between groups was noted. Conclusions Intraperitoneal therapy with paclitaxel and cisplatin, as compared with dose-dense paclitaxel and carboplatin, did not prolong progression-free or overall survival in the adjuvant setting among stage III ovarian cancer patients. A trend towards decreased tolerability was noted with intraperitoneal therapy.


Author(s):  
Pavani Chalasani ◽  
Kiah Farr ◽  
Vicky Wu ◽  
Isaac Jenkins ◽  
Alex Liu ◽  
...  

Abstract Background Treatment options for metastatic breast cancer (MBC) refractory to anthracyclines and taxanes are limited. In a phase III trial, eribulin demonstrated a significant improvement in overall survival compared to treatment of physician’s choice, but had limited tolerability because of neutropenia and peripheral neuropathy. Based on prior studies of alternative treatment schedules with other therapies, we hypothesized that a low-dose metronomic schedule of eribulin would permit patients to remain on treatment more consistently without treatment delays, resulting in longer time to progression, and improved toxicity profile. Methods We conducted a multi-site single arm, phase II trial patients with MBC. All patients were treated with metronomic eribulin (0.9 mg/m2 administered intravenously on days 1, 8, and 15 of a 28-day cycle.) Treatment was continued until the patient developed disease progression, unacceptable toxicity, or chose to stop the study. Patients must have had prior taxane exposure. The primary endpoint was progression-free survival. Secondary end points were overall survival, response rate, and clinical benefit rate. Exploratory biomarkers were performed to analyze change in levels of circulating endothelial cells (CECs), circulating endothelial precursors, and carbonic anhydrase IX (CAIX) with response to therapy. Findings We consented 86 patients and 59 were evaluable for final analysis. Median age was 59 years; 78% had HER2 negative tumors. The median progression-free survival (PFS) was 3.5 months with overall survival (OS) of 14.3 months. Objective response rate was 15% with clinical benefit rate of 48%. Reported grade 3 neutropenia and peripheral neuropathy were 18% and 5%, respectively. Treatment discontinuation due to toxicity was seen in 3% of patients. Interpretation Metronomic weekly low-dose eribulin is an active and tolerable regimen with significantly less myelosuppression, alopecia, and peripheral neuropathy than is seen with the approved dose and schedule, allowing longer duration of use and disease control, with similar outcomes compared to the standard dose regimen.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingduo Kong ◽  
Hongyi Wei ◽  
Jing Zhang ◽  
Yilin Li ◽  
Yongjun Wang

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.


2014 ◽  
Vol 24 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Alejandra Martínez ◽  
Cristophe Pomel ◽  
Thomas Filleron ◽  
Marjolein De Cuypere ◽  
Eliane Mery ◽  
...  

ObjectiveThe aim of the study was to report on the oncologic outcome of the disease spread to celiac lymph nodes (CLNs) in advanced-stage ovarian cancer patients.MethodsAll patients who had CLN resection as part of their cytoreductive surgery for epithelial ovarian, fallopian, or primary peritoneal cancer were identified. Patient demographic data with particular emphasis on operative records to detail the extent and distribution of the disease spread, lymphadenectomy procedures, pathologic data, and follow-up data were included.ResultsThe median follow-up was 26.3 months. The median overall survival values in the group with positive CLNs and in the group with negative CLNs were 26.9 months and 40.04 months, respectively. The median progression-free survival values in the group with metastatic CLNs and in the group with negative CLNs were 8.8 months and 20.24 months, respectively (P = 0.053). Positive CLNs were associated with progression during or within 6 months after the completion of chemotherapy (P = 0.0044). Tumor burden and extensive disease distribution were significantly associated with poor progression-free survival, short-term progression, and overall survival. In multivariate analysis, only the CLN status was independently associated with short-term progression.ConclusionsDisease in the CLN is a marker of disease severity, which is associated to a high-risk group of patients with presumed adverse tumor biology, increased risk of lymph node progression, and worst oncologic outcome.


2018 ◽  
Vol 25 (6) ◽  
pp. 1301-1304 ◽  
Author(s):  
Mário L de Lemos ◽  
Isabell Kang ◽  
Kimberly Schaff

Background Patients with locally advanced, recurrent or metastatic solitary fibrous tumour are often treated with bevacizumab and temozolomide based on the clinical efficacy reported in a case series of 14 patients. Given the rarity of solitary fibrous tumour, large trials are not feasible. We report the efficacy of this regimen based on a population-based analysis. Methods This was a population-based retrospective, multi-centre analysis using patient data from a provincial cancer registry and treatment database. Cases from June 2006 through October 2016 were identified for patients receiving bevacizumab and temozolomide for locally advanced, recurrent or metastatic solitary fibrous tumour or hemangiopericytoma, which is sometimes used to describe tumours arising from the meninges. The primary outcome was overall response rate. Secondary outcomes included time to response, progression free survival and overall survival estimated using the Kaplan–Meier method. Results Fourteen patients were identified: median age 59 (range 44–70), male 78.6%. Diagnoses were solitary fibrous tumour in 10 (71.4%) and hemangiopericytoma in four (28.6%), with metastatic disease in 10 (72.7%) patients. The most common primary sites were meninges in four (28.6%) and pelvis in three (21.4%) patients. The median follow-up was 15.5 months, with median treatment of four months. Overall response rate was 21.4% (no complete response, 3 partial response), with median time to response of four months. Median progression free survival, six-month progression free survival and overall survival were 17 months, 65.0%, and 45 months, respectively. Conclusions Efficacy of bevacizumab and temozolomide in solitary fibrous tumour appeared to be similar to that previously reported. Our findings confirmed that bevacizumab and temozolomide is an effective and tolerated treatment for this patient population.


Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1013
Author(s):  
Chara Papadaki ◽  
Stavroula Manolakou ◽  
Eleni Lagoudaki ◽  
Spyros Pontikakis ◽  
Despo Ierodiakonou ◽  
...  

CD44, a surface marker for cancer stem cells, interacts with PKM2, a key regulator of aerobic glycolysis, and enhances the glycolytic phenotype of cancer cells leading to antioxidant protection and macromolecules’ synthesis. To clarify the clinical importance of this “cross-talk” as a mechanism of drug resistance, we assessed the expression both of PKM2 and of CD44 in cancer cells of patients with epithelial ovarian cancer (EOC) treated with platinum-based treatment. One hundred and seventy-one patients with EOC were assessed for PKM2mRNA expression and PKM2 and CD44 proteins detection. Associations with progression-free survival (PFS) and overall survival (OS) were assessed with Kaplan–Meier and adjusted Cox regression models. PKM2mRNA and protein as well as CD44 protein were detectable in the majority of patients. Positive correlation between PKM2 and CD44 protein expression was observed (Spearman rho = 0.2, p = 0.015). When we used the median to group patients into high versus low expression, high PKM2mRNA and protein levels were significantly associated with lower progression-free survival (PFS; p = 0.003 and p = 0.002, respectively) and shorter overall survival (OS; p ≤ 0.001 and p = 0.001, respectively). However, high CD44 protein expression was significantly correlated only with shorter OS (p = 0.004). Moreover, patients with both high PKM2 and CD44 protein levels experienced shorter PFS and OS (p = 0.007 and p = 0.003, respectively) compared to patients with low expression of both proteins. Finally, higher PKM2mRNA and protein expression as well as CD44 protein expression (HR: 2.16; HR: 1.82; HR: 1.01, respectively) were independent prognostic factors for decreased median OS (mOS), whereas only PKM2 protein expression (HR: 1.95) was an independent prognostic factor for decreased median PFS (mPFS). In conclusion, PKM2 expression is a negative prognostic factor in EOC patients, but the interaction between CD44 and PKM2 that may be implicated in EOC platinum-resistance needs further investigation.


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