Weekly carboplatin and paclitaxel is safe, active, and well tolerated in recurrent ovarian cancer cases of Japanese women previously treated with cisplatin-containing multidrug chemotherapy

2005 ◽  
Vol 15 (1) ◽  
pp. 45-49 ◽  
Author(s):  
A. Kikuchi ◽  
H. Sakamoto ◽  
T. Yamamoto
Keyword(s):  
Ovarian Cancer ◽  
Therapeutic Index ◽  
Complete Response ◽  
Japanese Patients ◽  
Japanese Women ◽  
Toxicity Profile ◽  
Term Survival ◽  
Ovarian Cancers ◽  
Platinum Based Chemotherapy ◽  
Multidrug Chemotherapy

The safety and efficacy of weekly carboplatin and paclitaxel administration in recurrent ovarian cancers after platinum-containing multidrug chemotherapy were tested. Japanese patients who achieved complete response with surgery and adjuvant platinum-based chemotherapy and who had a recurrence after at least 6 months were included in the case – control study. Twenty-seven cases received the weekly TJ (WTJ) regime (cohort 1: T = 80 mg/m2, J = AUC 2, median course = 13, range = 3–26) and 41 received other regimens [cohort 2: CAP = 37, monthly TJ (MTJ) = 4]. Toxicity profile, response rate, therapeutic index (TI), and survival were analyzed. Neutropenia, thrombocytopenia, and peripheral neuropathy (grades 3 and 4) in cohorts 1 and 2 were 1.7% and 90%, 5.1% and 14.3%, and 0% and 4.8%, respectively. Response rates were 77.8% and. Thus, TI of the two cohorts was 3.9 and 1.9, respectively. The median survival of cohort 1 was 48.3 months (95% CI 11.5–85.0) whereas that of cohort 2 was 17.8 months (95% CI 5.3–30.3, P < 0.005). WTJ has better toxicity profile and TI than monthly platinum-based multidrug regimens for recurrent ovarian cancers in Japanese women. As second-line treatment of ovarian cancer should primarily provide high TI, WTJ regimen appears a better candidate, but its long-term survival benefit should be tested against MTJ.

Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission

2021 ◽  
pp. ijgc-2020-002239
Author(s):  
Oren Smaletz ◽  
Gustavo Ismael ◽  
Maria Del Pilar Estevez-Diz ◽  
Ivana L O Nascimento ◽  
Ana Luiza Gomes de Morais ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibody ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Lewis Y

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

scholarly journals Therapeutic Targeting of Collective Invasion in Ovarian Cancer

2019 ◽  
Vol 20 (6) ◽  
pp. 1466 ◽  
Author(s):  
Laura Moffitt ◽  
Nazanin Karimnia ◽  
Andrew Stephens ◽  
Maree Bilandzic
Keyword(s):  
Ovarian Cancer ◽  
Primary Tumour ◽  
Survival Rates ◽  
Cell Types ◽  
Target Tissue ◽  
Multicellular Spheroids ◽  
Epithelial Cancers ◽  
Ovarian Cancers ◽  
Platinum Based Chemotherapy ◽  
Collective Invasion

Ovarian cancer is the seventh most commonly diagnosed cancer amongst women and has the highest mortality rate of all gynaecological malignancies. It is a heterogeneous disease attributed to one of three cell types found within the reproductive milieu: epithelial, stromal, and germ cell. Each histotype differs in etiology, pathogenesis, molecular biology, risk factors, and prognosis. Furthermore, the origin of ovarian cancer remains unclear, with ovarian involvement secondary to the contribution of other gynaecological tissues. Despite these complexities, the disease is often treated as a single entity, resulting in minimal improvement to survival rates since the introduction of platinum-based chemotherapy over 30 years ago. Despite concerted research efforts, ovarian cancer remains one of the most difficult cancers to detect and treat, which is in part due to the unique mode of its dissemination. Ovarian cancers tend to invade locally to neighbouring tissues by direct extension from the primary tumour, and passively to pelvic and distal organs within the peritoneal fluid or ascites as multicellular spheroids. Once at their target tissue, ovarian cancers, like most epithelial cancers including colorectal, melanoma, and breast, tend to invade as a cohesive unit in a process termed collective invasion, driven by specialized cells termed “leader cells”. Emerging evidence implicates leader cells as essential drivers of collective invasion and metastasis, identifying collective invasion and leader cells as a viable target for the management of metastatic disease. However, the development of targeted therapies specifically against this process and this subset of cells is lacking. Here, we review our understanding of metastasis, collective invasion, and the role of leader cells in ovarian cancer. We will discuss emerging research into the development of novel therapies targeting collective invasion and the leader cell population.

Functional profiling of clear cell ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5035-5035
Author(s):  
Rowan Miller ◽  
Rachel Brough ◽  
Ilirjana Bajrami ◽  
Stanley B. Kaye ◽  
Christopher J. Lord ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Throughput Screening ◽  
Clear Cell ◽  
Integral Functional ◽  
Therapeutic Targets ◽  
Molecular Profiling ◽  
Loss Of Function ◽  
Ovarian Carcinomas ◽  
Ovarian Cancers ◽  
Platinum Based Chemotherapy

5035 Background: Clear cell ovarian cancer represents up to 15% of epithelial ovarian cancers. In comparison to other subtypes, clear cell ovarian carcinomas have a poorer prognosis and are relatively resistant to standard platinum based chemotherapy. Recently, loss of function mutations in the tumour suppressor gene ARID1A were identified in up to 50% of ovarian clear cell carcinomas. We have adopted an integral functional and molecular profiling approach as a route to identify new genetic dependencies and therapeutic targets for this disease. Methods: Clear cell ovarian cancer cell lines were functionally profiled using high throughput screening with chemical and siRNA libraries. This has been integrated with molecular profiling data generated from exome and transcriptome sequencing to aid the discovery of novel targets. Results: Using functional screens we have now identified critical gene dependencies and potential therapeutics in a series of clear cell ovarian cancer models. The comparison of functional viability profiles for models characterized by ARID1A loss of function mutations is now enabling an analysis of synthetic lethal effects that could be used to target clear cell ovarian cancers carrying these mutations. Conclusions: The work undertaken so far provides the framework for the discovery of therapeutic targets for clear cell ovarian cancer using an integrated approach. Revalidation of these preliminary results is now underway to characterize new genetic dependencies for this disease.

Weekly topotecan and biweekly bevacizumab in recurrent and progressive ovarian carcinoma: A single institution experience for third-line or greater treatment.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16553-e16553
Author(s):  
Kassondra S Grzankowski ◽  
Shashikant B. Lele ◽  
John Pietkiewicz
Keyword(s):  
Ovarian Cancer ◽  
Adverse Events ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Toxicity Profile ◽  
Single Institution ◽  
Free Survival ◽  
Early Use ◽  
Third Line

e16553 Background: The toxicity and efficacy of combined weekly topotecan and weekly bevacizumab in women with recurrent and progressive ovarian cancer. Methods: Reviewed data-base from 1/2003-present (1/2013) identified 15 patients who were treated with topotecan 4mg/m2 on days 1, 8, and 15 and bevacizumab 10mg/kg on days 1 and 15 of a 28-day cycle until progressive disease or excessive toxicity warranted discontinuation. The primary endpoint was progression-free survival. Results: Patients (n = 15) received a median of 4 treatment cycles. Mean number of previous chemotherapy regimens was 5 (range 2-9). Toxicity was generally mild, with neutropenia (20%), gastrointestinal toxicity (20%), pain (26%), anemia requiring transfusion (6%) being the most common adverse events. Two patients required dose adjustment secondary to neutropenia. Patients treated with 5 or more prior regimens had more adverse events, 66% vs. 33%, respectively. No febrile neutropenia or treatment-related deaths occurred. Median PFS and OS were 5.6 months and 5.9 months with 6 (40%) patients progression-free for ≥5 months. Two (13%) patients had complete response, 9 (60%) had stable disease or partial response and were still receiving the above mentioned treatment, and 4 (27%) had progressive disease. Conclusions: Treatment of recurrent and progressive ovarian cancer with weekly Topotecan and biweekly Bevacizumab demonstrates a viable efficacy with acceptable toxicity profile in women with previous multiple lines of treatment; as this becomes a more widely used regimen further investigation will be needed to determine early use of this well tolerated chemotherapy.

Impact of BRCA mutation status and time to platinum resistance on patients with advanced ovarian cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5561-5561
Author(s):  
Alexandra Tyulyandina ◽  
Maxim Filipenko ◽  
Alexey Rumyantsev ◽  
Ilya Pokataev ◽  
Valentina Nechushkina ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Brca Mutation ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Platinum Resistance ◽  
Term Survival ◽  
Mutation Status ◽  
Platinum Based Chemotherapy ◽  
Significant Difference

5561 Background: The influence of germline BRCA1/2 mutations (gBRCAmt) on ovarian cancer patients (pts) long-term survival remains controversial. Methods: 228 pts with serous and endometrial ovarian cancer stage Ic-IV were enrolled in the retrospective study. Next-generation sequencing testing of BRCA1/2 in blood was employed. Progression-free survival (PFS), overall survival (OS) and time to platinum resistance (TPR) were analyzed. TPR was defined as time from first line chemotherapy to registration of platinum resistance relapse. Results: The rate of pathogenic gBRCAmt was defined in 29.4% (67/228) pts. There was no any significant difference between BRCA1/2 mutation carries and non-carries in both PFS (18.3 and 16.7 months, p = 0.27, HR 0.79, 95%CI 0.52-1.20) and OS (71.9 and 79.1 months, p = 0.69, HR 0.88, 95%CI 0.46-1.68). However, TPR was significantly longer in pts with gBRCAmt than in germline BRCA wild type (gBRCAwt) pts (51.4 and 34.4 months, p = 0.05, HR 0.60, 95% CI 0.36-0.98). Pts with gBRCAmt had poor prognosis after registration of platinum resistance. gBRCAwt pts had longer survival than gBRCAmt after platinum-resistance relapse: 33.7 and 16.9 months respectively (p = 0.05; HR 1.85, 95%CI 1.02-4.08). Conclusions: Our finding provided possible explanation of equal survival of pts with or without BRCA1/2 mutations. Long-term sensitivity to platinum-based chemotherapy allowed pts with gBRCA1/2mt to control the disease for a long period of time. However the non-platinum regimens had less efficacy in pts with gBRCAmt than gBRCAwt after platinum resistance.

Phase III Trial of Observation Versus Six Courses of Paclitaxel in Patients With Advanced Epithelial Ovarian Cancer in Complete Response After Six Courses of Paclitaxel/Platinum-Based Chemotherapy: Final Results of the After-6 Protocol 1

2009 ◽  
Vol 27 (28) ◽  
pp. 4642-4648 ◽  
Author(s):  
Sergio Pecorelli ◽  
Giuseppe Favalli ◽  
Angiolo Gadducci ◽  
Dionyssios Katsaros ◽  
Pierluigi Benedetti Panici ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Complete Response ◽  
First Line ◽  
Free Survival ◽  
Consolidation Treatment ◽  
Platinum Based Chemotherapy ◽  
Advanced Epithelial Ovarian Cancer

Purpose To assess whether six courses of paclitaxel are effective as consolidation treatment in patients with advanced epithelial ovarian cancer who are in complete response after first-line paclitaxel/platinum–based chemotherapy. Patients and Methods Patients with stages IIb to IV disease in clinical or pathologic complete response after six courses of paclitaxel/platinum–based chemotherapy were randomly allocated to either observation (ie, control) or six courses of paclitaxel 175 mg/m2 every 3 weeks (ie, maintenance). Results Two hundred patients were randomly assigned from March 1999 to July 2006. Because of the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Grade 2 or greater motor neurotoxicity and sensory neurotoxicity were reported in 11.3% and 28.0% of the paclitaxel-arm patients, respectively. After a median follow-up of 43.5 months, 107 patients (53%) had experienced relapse, and 48 patients (24%) had died. Two-year progression-free survival rates were 54% (95% CI, 43% to 64%) and 59% (95% CI, 49% to 69%; P = not significant) in the control and maintenance arms, respectively. Corresponding 2-year overall survival rates were 90% (95% CI, 84% to 97%) and 87% (95% CI, 80% to 94%; P = not significant), respectively. The Cox model showed that residual disease after initial surgery (macroscopic v no macroscopic residuum; hazard ratio [HR], 1.91; 95%CI, 1.21 to 3.03) and stage (IIIc to IV v others; HR, 3.10; 95% CI, 1.13 to 8.48) were independent prognostic factors for progression-free survival, whereas the treatment arm (maintenance v control) had no prognostic relevance. Conclusion A consolidation treatment with six cycles of paclitaxel does not prolong progression-free survival or overall survival in patients in complete response after first-line paclitaxel/platinum–based regimens.

The role of anthracyclines in second-line therapy of ovarian cancer

2003 ◽  
Vol 13 (Suppl 2) ◽  
pp. 178-184 ◽  
Author(s):  
J. B. Vermorken
Keyword(s):  
Ovarian Cancer ◽  
Randomized Trials ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Second Line ◽  
Toxicity Profile ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

Anthracyclines (ANTs) have been in clinical practice since the 1960s and represent one of the most commonly used classes of anticancer drugs. In the 1990s, meta-analyses showed a favorable impact of doxorubicin (DOX/A) on the survival of patients with advanced ovarian cancer, when it was combined with cyclophosphamide and cisplatin (CAP) and compared to CP alone. With the acceptance of paclitaxel-carboplatin (TCb) as the new reference arm for first-line treatment, testing the addition of ANTs to TCb seems a logic next step. Trials presently testing this, make use of either epirubicin (EPI) or pegylated liposomal doxorubicin (PLD: Doxil®/Caelyx®). These are the two most favorable ANTs, based on data obtained with various ANTs in ovarian cancer failing platinum-based chemotherapy. EPI has not been evaluated in direct comparison with other antineoplastic agents. PLD has been compared with both paclitaxel and topotecan. No difference in efficacy parameters could be observed, but the toxicity profile of PLD scored favorably against those of the comparator in both trials, despite the fact that palmar-plantar erythrodysesthesia can be troublesome, and sometimes lead to treatment discontinuation. Data from four randomized trials evaluating the role of ANT combinations in patients with relapsed ovarian cancer suggest that the addition of EPI or DOX to paclitaxel does not lead to better outcomes in patients with platinum-refractory or resistant disease. In platinum-sensitive disease, any benefit of EPI-platinum or DOX-platinum combinations over platinum alone is uncertain. There are no randomized trials with PLD combinations in the second-line setting. It is concluded that both EPI and PLD can be recommended as a reasonable single-agent treatment option for relapsed patients, with a preference for PLD taking into account its more favorable toxicity profile.

Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer.

1992 ◽  
Vol 10 (5) ◽  
pp. 706-717 ◽  
Author(s):  
D S Alberts ◽  
S Green ◽  
E V Hannigan ◽  
R O'Toole ◽  
D Stock-Novack ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Pathologic Complete Response ◽  
Stage Iv ◽  
Therapeutic Index ◽  
Response Rates ◽  
Complete Response ◽  
Phase Iii ◽  
Stage Iii ◽  
Final Report ◽  
Nausea And Emesis

PURPOSE To compare cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide as primary chemotherapy for stage III (suboptimal) and stage IV ovarian cancer. PATIENTS AND METHODS Three hundred forty-two patients were randomly assigned to treatment with six courses of intravenous (i.v.) cisplatin 100 mg/m2 plus i.v. cyclophosphamide 600 mg/m2, or i.v. carboplatin 300 mg/m2 plus i.v. cyclophosphamide 600 mg/m2. RESULTS The estimated median survivals were 17.4 and 20.0 months for the cisplatin and carboplatin study arms, respectively. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the P = .02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. Pathologic complete response rates were similar for both study arms. There was less thrombocytopenia on the cisplatin arm (P less than .001); however, there was less nausea and emesis (P less than or equal to .001 for courses 1 to 5), renal toxicity (P less than .001), anemia (P = .01), hearing loss (P less than .001), tinnitus (P = .01), neuromuscular toxicities (P = .001), and alopecia (P less than .001) on the carboplatin arm. CONCLUSION Carboplatin-cyclophosphamide proved to have a significantly better therapeutic index than cisplatin-cyclophosphamide in patients with stage III (suboptimal) and stage IV ovarian cancer.

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