Oral Topotecan as Single-Agent Second-Line Chemotherapy in Patients With Advanced Ovarian Cancer

2001 ◽  
Vol 19 (19) ◽  
pp. 3967-3975 ◽  
Author(s):  
D. L. Clarke-Pearson ◽  
L. Van Le ◽  
T. Iveson ◽  
C. W. Whitney ◽  
P. Hanjani ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Median Time ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Prolonged Treatment ◽  
Second Line ◽  
Gynecology And Obstetrics ◽  
Platinum Based Chemotherapy ◽  
Oral Topotecan

PURPOSE: To evaluate oral topotecan as single-agent, second-line therapy in patients with ovarian cancer previously treated with a platinum-based regimen. PATIENTS AND METHODS: Patients (N = 116) received oral topotecan 2.3 mg/m2 daily for 5 days every 21 days. Eligibility criteria included histologic diagnosis of International Federation of Gynecology and Obstetrics stage III or IV epithelial ovarian cancer, bidimensionally measurable disease, prior platinum-containing chemotherapy, age ≥ 18 years, performance status ≤ 2, and life expectancy ≥ 12 weeks. RESULTS: Overall response rate was 21.6% (25 of 116 patients). Median duration of response was 25.0 weeks; median time to response was 8.4 weeks. Median time to progression was 14.1 weeks; median survival was 62.2 weeks. Grade 4 neutropenia was experienced by 50.4% of patients in 13.4% of courses administered. Grade 4 thrombocytopenia was experienced by 22.1% of patients in 5.1% of courses. Grade 3 or 4 anemia was experienced by 29.2% of patients in 8.5% of courses. Most frequent nonhematologic toxicities were predominantly (> 90%) grade 1 or 2 and included nausea, alopecia, diarrhea, and vomiting. CONCLUSION: Second-line oral topotecan administered at 2.3 mg/m2 for 5 days every 21 days demonstrated activity in patients with progressive or recurrent ovarian cancer after first-line platinum-based chemotherapy. This activity was comparable to that seen in previous studies with intravenous topotecan. Grade 4 neutropenia was less frequent with oral topotecan than previously reported for intravenous topotecan. Oral topotecan is an active, tolerable, and convenient formulation of an established agent for the second-line treatment of advanced epithelial ovarian cancer and may also facilitate exploring prolonged treatment schedules.

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.

Multicenter Phase 2 Study of Combined Gemcitabine and Epirubicin as Second-Line Treatment for Patients With Advanced Ovarian Cancer

2010 ◽  
Vol 20 (6) ◽  
pp. 953-957 ◽  
Author(s):  
Viviana Murgia ◽  
Roberto Sorio ◽  
Claudia Griso ◽  
Orazio Caffo ◽  
Carmela Arcuri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Ovarian Cancer ◽  
Hematological Toxicity ◽  
Line Treatment ◽  
Second Line ◽  
Phase 2 ◽  
Platinum Resistant ◽  
Gynecology And Obstetrics

Objective:The aim of this phase 2 trial was to evaluate the tolerability and efficacy of combined gemcitabine (G) and epirubicin (E) as second-line treatment for patients with advanced ovarian cancer.Methods:Treatment with G 1000 mg/m2 (days 1 and 8) and E 60 mg/m2 (day 1) every 3 weeks for 3 or, in the absence of progression, 6 courses.Results:Fifty patients with advanced ovarian cancer (31 serous, 2 endometrioid, 10 unclassified adenocarcinoma, and 7 other) and a median age of 60 years (range, 38-74 years) were enrolled after giving their informed consent. Performance status according to the Eastern Cooperative Oncology Group was 0 in 29 patients (58%), 1 in 17 patients (34%), and 2 in 4 patients (8%), and the initial stages according to the International Federation of Gynecology and Obstetrics were I to II in 4 patients (8%), III in 31 patients (62%), and IV in 15 patients (30%). They had previously received a median of 1.5 lines of treatment (range, 1-4). The median platinum-free interval was 5 months (range, 0-12 months): 32 patients had relapse within 6 months and 18 patients had relapse after 6 months.The response rate was 42% (2% complete response and 40% partial response), with a median duration of 7.2 months: the corresponding figures were 37.5% and 5.2 months in the platinum-resistant patients and 50% and 8.8 months in the platinum-sensitive patients. The main grade 3 to 4 hematological toxicity was neutropenia (56% of cases). After a median follow-up of 13.5 months, median progression-free survival was 5 months, and median overall survival was 23.5 months.Conclusions:This E + G combination seems to be active and safe in platinum-resistant/refractory patients.

DUETTE: A randomized phase II study to assess a second maintenance treatment with olaparib (ola) or ola+ceralasertib (cer), in patients (pts) with platinum-sensitive relapsed (PSR) epithelial ovarian cancer who have previously received PARP inhibitor maintenance treatment (NCT04239014).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS6104-TPS6104 ◽  
Author(s):  
Amit M. Oza ◽  
Andrew Pierce ◽  
Alan Lau ◽  
Nisha Kurian ◽  
Graeme Parr ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Maintenance Treatment ◽  
Phase Ii Study ◽  
Brca Mutation ◽  
Unmet Need ◽  
Advanced Ovarian Cancer ◽  
Resistance Mechanisms ◽  
Platinum Based Chemotherapy

TPS6104 Background: Ovarian cancer is the leading cause of death from gynecological cancers in the USA, and the fifth most common cause of cancer death in women. Ola is a PARPi approved for first-line maintenance treatment of BRCA-mutated advanced ovarian cancer in women who achieve a complete or partial response to platinum-based chemotherapy. Ola is also efficacious in combination with bevacizumab in the same population, independent of BRCA mutation status. Cer is a potent, oral, selective inhibitor of ATR. ATR is a critical DDR kinase that is activated in response to replication stress and stalled replication forks. There is no second maintenance standard of care for patients with PSR ovarian cancer who have previously received a PARPi in the maintenance setting. Pre-clinical models have shown that several mechanisms of PARPi resistance may be overcome by ATR inhibition, such as BRCA reversion, replication fork protection and DDR rewiring. DUETTE will select pts with tumor response or stable disease after second or third-line platinum-based treatment, with the expectation to enrich for non-BRCA reversion PARPi resistance mechanisms. The study will address the role of a second maintenance treatment following prior 1L or 2L maintenance, an emerging population of unmet need, and includes translational studies that aim to further our knowledge of clinical PARPi resistance mechanisms and predictors of treatment response. Methods: DUETTE is a global, multi-center, phase II study. 192 pts with PSR epithelial ovarian cancer who have previously received PARPi maintenance treatment, will be retreated with platinum and those who have not progressed after ≥ 4 cycles will be randomized (1:1:1) to 3 treatment arms: Arm 1, open-label: cer 160 mg once daily (qd) days 1 to 7 plus ola 300 mg twice daily (bd); Arm 2, blinded: ola monotherapy 300 mg bd and Arm 3, blinded: ola-placebo. Treatment is administered in 28-day cycles. All pts will be stratified by BRCA status (mutation or wildtype) and response to most recent line of platinum-based chemotherapy (CR/PR or SD). The primary endpoint is to assess the efficacy of maintenance ola monotherapy and cer+ola combination therapy compared with placebo by PFS using blinded, independent central review. Secondary endpoints are overall survival, PFS2, ORR, DoR, safety and tolerability. Enrolment is planned to start in April 2020.

Randomized trial of dose-intensity with single-agent carboplatin in patients with epithelial ovarian cancer. London Gynaecological Oncology Group.

1998 ◽  
Vol 16 (7) ◽  
pp. 2426-2434 ◽  
Author(s):  
M Gore ◽  
P Mainwaring ◽  
R A'Hern ◽  
V MacFarlane ◽  
M Slevin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Total Dose ◽  
Single Agent ◽  
Dose Intensity ◽  
Hematologic Toxicity ◽  
Dose Increase ◽  
Gynecology And Obstetrics ◽  
Carboplatin Auc

PURPOSE We have examined the role of an increase in cisplatin dose-intensity in patients with advanced epithelial ovarian cancer by means of single-agent carboplatin therapy. PATIENTS AND METHODS Two hundred twenty-seven patients were randomized to treatment and eligible for analysis. The dose of carboplatin was calculated according to the Calvert formula. One hundred seventeen patients received carboplatin at an area under the concentration time curve (AUC) of 6 for six courses, administered every 28 days, and 110 patients received carboplatin at an AUC of 12 for four courses, administered every 28 days. Patients were eligible provided they had not received prior chemotherapy or radiotherapy and had International Federation of Gynecology and Obstetrics stages II to IV or relapsed stage I epithelial ovarian cancer. RESULTS The planned total-dose increase was 33% for the patients treated with carboplatin AUC 12, but the received percentage total-dose increase was 20%. There were no differences in progression-free or overall survival between the two treatment arms; the overall survival rate at 5 years was 31% and 34% of patients treated at AUCs 6 and 12, respectively. There was significantly more toxicity associated with carboplatin AUC 12, which resulted in more treatment delays and/or dose reductions (52% v 18%; P < .001). CONCLUSION We have shown that carboplatin can be delivered at an AUC of 12 for four courses without granulocyte colony-stimulating factor support, although significant hematologic toxicity occurs. Nonhematologic toxicities were not clinically significant. Carboplatin offers an opportunity to intensify cisplatin therapy, but a greater than two-fold increase in dose-intensity probably needs to be achieved before significant effects on survival will be produced and hematologic support will be required.

Second-line therapy of advanced ovarian cancer with GnRH analogs

2004 ◽  
Vol 14 (5) ◽  
pp. 799-803 ◽  
Author(s):  
G. Balbi ◽  
L. D. Piano ◽  
A. Cardone ◽  
G. Cirelli
Keyword(s):  
Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Ca 125 ◽  
Second Line ◽  
Second Line Therapy ◽  
Gnrh Analogs ◽  
Line Therapy ◽  
Platinum Based Chemotherapy ◽  
Previously Treated

Ovarian cancer is still the first cause of death among female malignancies. The standard treatment adopted in ovarian cancer is a radical surgical treatment or cytoreduction, followed by six courses of platinum-based chemotherapy; second-line regimens are associated with severe side effects. GnRH analogs could represent an alternative therapeutical approach. The aim of our study was to evaluate the role of GnRH analogs in the management of platinum-resistant ovarian cancers. We enrolled 12 patients affected by advanced ovarian cancer, previously treated with six courses of platinum–paclitaxel. In second-line therapy, we used leuprolide on 1, 8, and 28 days of treatment. CA 125 levels were recorded for each patient. One case of clinical partial response was obtained (8.3%). Stable disease was diagnosed in three patients (25%). Progression was recorded in eight cases (66.7%). Progression-free survival was 6 months. The treatment was well tolerated by patients. The high tolerability and the results obtained with leuprolide versus platinum in second-line therapy might permit a better use of the analogs for advanced ovarian cancer.

scholarly journals Treatment of Recurrent Epithelial Ovarian Cancer

2020 ◽  
Vol 80 (12) ◽  
pp. 1195-1204
Author(s):  
Carlota Claussen ◽  
Achim Rody ◽  
Lars Hanker
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Epithelial Ovarian Cancer ◽  
Tumor Biology ◽  
Advanced Ovarian Cancer ◽  
Parp Inhibitors ◽  
Free Interval ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
New Findings

AbstractEpithelial ovarian cancer is the most common cause of death from gynecological tumors. Most patients with advanced ovarian cancer develop recurrence after concluding first-line therapy, making further lines of therapy necessary. The choice of therapy depends on various criteria such as tumor biology, the patientʼs general condition (ECOG), toxicity, previous chemotherapy, and response to chemotherapy. The platinum-free or treatment-free interval determines the potential response to repeat platinum-based therapy. If patients have late recurrence, i.e. > 6 months after the end of the last platinum-based therapy (i.e., they were previously platinum-sensitive), then they are usually considered suitable for another round of a platinum-based combination therapy. Patients who are not considered suitable for platinum-based chemotherapy are treated with a platinum-free regimen such as weekly paclitaxel, pegylated liposomal doxorubicin (PLD), gemcitabine, or topotecan. Treatment for the patient subgroup which is considered suitable for platinum-based therapy but cannot receive carboplatin due to uncontrollable hypersensitivity reactions may consist of trabectedin and PLD. While the use of surgery to treat recurrence has long been a controversial issue, new findings from the DESKTOP III study of the AGO working group have drawn attention to this issue again, particularly for patients with a platinum-free interval of > 6 months and a positive AGO score. Clinical studies have also shown the efficacy of angiogenesis inhibitors such as bevacizumab and the PARP inhibitors olaparib, niraparib and rucaparib. These drugs have substantially changed current treatment practice and expanded the range of available therapies. It is important to differentiate between purely maintenance therapy after completing CTX, continuous maintenance therapy during CTX, and the therapeutic use of these substances. The PARP inhibitors niraparib, olaparib and rucaparib have already been approved for use by the FDA and the EMA. The presence of a BRCA mutation is a predictive factor for a better response to PARP inhibitors.

Clinical Utility of CA-125 for Maintenance Therapy in the Treatment of Advanced Stage Ovarian Carcinoma

2009 ◽  
Vol 19 (2) ◽  
pp. 239-241 ◽  
Author(s):  
John P. Micha ◽  
Bram H. Goldstein ◽  
Mark A. Rettenmaier ◽  
John V. Brown ◽  
Cameron R. John ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Ovarian Carcinoma ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Complete Response ◽  
Ca 125 ◽  
Advanced Stage ◽  
Therapy Regimen ◽  
Platinum Based Chemotherapy

AbstractMaintenance therapy has been extensively studied to discern any prospective therapeutic advantage in the treatment of advanced stage ovarian carcinoma. The CA-125 assay may have prognostic benefit in determining whether this treatment regimen is appropriate for ovarian carcinoma patients who achieve a complete response to first-line therapy. We retrospectively documented the CA-125 levels of 2 advanced ovarian cancer patient groups who exhibited a clinically defined complete response to their primary induction therapy. Patients were then treated with a paclitaxel-based maintenance therapy regimen. The first group (group A; n = 13 patients) received 3 cycles of single-agent paclitaxel maintenance therapy, and the second group (group B; n = 13 patients) received 12 cycles of single-agent paclitaxel maintenance therapy. The premaintenance therapy CA-125 serum levels (<10 or ≥10 U/mL) of the 2 treatment groups were then retrospectively evaluated in an intragroup analysis to discern any relationship with progression-free survival (PFS) and overall survival. There was a statistically significantly relationship between the CA-125 levels (<10 U/mL) premaintenance therapy and PFS. The patients who had the lowest CA-125 levels exhibited the most favorable PFS results. Despite the limited sample size and nonrandomized nature of this study, these results are provocative and suggest that advanced ovarian cancer patients who achieve an excellent response to primary platinum-based chemotherapy with a CA-125 serum level less than 10 U/mL may be more amenable to the benefits of paclitaxel maintenance therapy.

Deregulation of miR-128 in Ovarian Cancer Promotes Cisplatin Resistance

2014 ◽  
Vol 24 (8) ◽  
pp. 1381-1388 ◽  
Author(s):  
Bing Li ◽  
Hong Chen ◽  
Nan Wu ◽  
Wen-Jing Zhang ◽  
Li-Xin Shang
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cisplatin Resistance ◽  
Ovarian Cancer Cell Line ◽  
Advanced Ovarian Cancer ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Ovarian Carcinomas ◽  
Platinum Based Chemotherapy ◽  
Skov3 Cells

ObjectivePlatinum-based chemotherapy is the standard treatment in advanced ovarian cancer, but most patients will relapse with drug-resistant disease. MicroRNAs have been demonstrated to function in chemoresistance in cancers. In this study, we focused on the role of miR-128 in cisplatin-resistant ovarian cancer.Materials and MethodsThe expression of miR-128 RNA and its targeted genes, the polycomb ring finger oncogene Bmi-1 and ATP-binding cassette subfamily C member 5 (ABCC5), were investigated in the epithelial ovarian cancer cells and ovarian carcinomas.ResultsmiR-128 expression was significantly reduced in the cisplatin-resistant human epithelial ovarian cancer cell line SKOV3/CP compared with parental SKOV3 cells and decreased upon treatment with cisplatin in a concentration-dependent manner in SKOV3, OVCAR3, and PEO14 cells. Overexpression of miR-128 resensitized SKOV3/CP cells to cisplatin and reduced the expression of cisplatin-resistant–related proteins ABCC5 and Bmi-1, whereas miR-128 inhibitors increased cisplatin resistance in SKOV3 cells. Cisplatin combined with miR-128 agomirs inhibited the growth of SKOV3/CP xenograft tumors more effectively than cisplatin alone. Diminished expression of ABCC5 and Bmi-1 and higher cisplatin concentrations were observed in tumor tissue of mice treated with miR-128 agomirs in addition to cisplatin.ConclusionsTaken together, our findings suggest that miR-128 may act as a promising therapeutic target for improvement of tumor sensitivity to cisplatin.

scholarly journals Impact of Provider Imaging Practices on Survival Outcomes in Advanced Ovarian Cancer

2020 ◽  
Vol 18 (4) ◽  
pp. 414-419 ◽  
Author(s):  
Angela K. Green ◽  
Deborah Korenstein ◽  
Carol Aghajanian ◽  
Brooke Barrow ◽  
Michael Curry ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Advanced Ovarian Cancer ◽  
Ca 125 ◽  
Study Cohort ◽  
Median Frequency ◽  
Time To Recurrence ◽  
Surveillance Imaging ◽  
Platinum Based Chemotherapy ◽  
Significant Difference

Background: This study sought to describe how high- versus low-frequency surveillance imaging practices among providers at Memorial Sloan Kettering Cancer Center (MSKCC) impact overall survival (OS) and time to recurrence of patients with advanced epithelial ovarian cancer in first remission. Methods: The study cohort included patients with stage II–IV high-grade epithelial ovarian cancer diagnosed in January 2001 through January 2017 who experienced recurrence after initial platinum-based chemotherapy. To determine usual imaging practices for providers at MSKCC, median frequency of CT or MRI of the abdomen/pelvis was calculated among patients with a long-term remission (defined as at least 1 year) treated by each provider. Cox proportional hazards models were used to examine differences in OS and time to recurrence among patients treated by providers with high versus low imaging frequency practices, with additional subgroup analysis among patients with elevated CA-125 levels >35 U/mL at diagnosis. Chi-square tests were used to examine differences in the proportion of patients who enrolled in clinical trials or underwent secondary cytoreductive surgery (SCS) by imaging frequency. Results: A total of 543 patients were treated by providers with high imaging frequency (>1 scan every 12 months) and 141 were treated by providers with low imaging frequency (≤1 scan every 12 months). Time to recurrence was shorter among patients treated by providers with high versus low imaging frequency (18.0 vs 19.2 months; hazard ratio, 1.33; P=.003). Results were similar when restricted to patients with elevated CA-125 levels at diagnosis. There was no significant difference in OS, clinical trial enrollment, or SCS by imaging practice. Conclusions: Within the limitations of this retrospective analysis, patients with advanced ovarian cancer treated by high-frequency-imaging providers had earlier detection of recurrence. Future analyses in a larger population are warranted to elucidate the risks versus benefits of surveillance imaging.

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