Gemcitabine Plus Carboplatin Compared With Carboplatin in Patients With Platinum-Sensitive Recurrent Ovarian Cancer: An Intergroup Trial of the AGO-OVAR, the NCIC CTG, and the EORTC GCG

2006 ◽  
Vol 24 (29) ◽  
pp. 4699-4707 ◽  
Author(s):  
Jacobus Pfisterer ◽  
Marie Plante ◽  
Ignace Vergote ◽  
Andreas du Bois ◽  
Hal Hirte ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Response Rate ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Primary Objective ◽  
Platinum Sensitive

Purpose Most patients with advanced ovarian cancer develop recurrent disease. For those patients who recur at least 6 months after initial therapy, paclitaxel platinum has shown a modest survival advantage over platinum without paclitaxel; however, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. Thus, an alternative regimen without significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer patients. Methods Patients with platinum-sensitive recurrent ovarian cancer were randomly assigned to receive either gemcitabine plus carboplatin or carboplatin alone, every 21 days. The primary objective was to compare progression-free survival (PFS). Results Three hundred fifty-six patients (178 gemcitabine plus carboplatin; 178 carboplatin) were randomly assigned. Patients received a median of six cycles in both arms. With a median follow-up of 17 months, median PFS was 8.6 months (95% CI, 7.9 to 9.7 months) for gemcitabine plus carboplatin and 5.8 months (95% CI, 5.2 to 7.1 months) for carboplatin. The hazard ration (HR) for PFS was 0.72 (95% CI, 0.58 to 0.90; P = .0031). Response rate was 47.2% (95% CI, 39.9% to 54.5%) for gemcitabine plus carboplatin and 30.9% (95% CI, 24.1% to 37.7%) for carboplatin (P = .0016). The HR for overall survival was 0.96 (95% CI, 0.75 to1.23; P = .7349). While myelosuppression was significantly more common in the combination, sequelae such as febrile neutropenia or infections were uncommon. No statistically significant differences in quality of life scores between arms were noted. Conclusion Gemcitabine plus carboplatin significantly improves PFS and response rate without worsening quality of life for patients with platinum-sensitive recurrent ovarian cancer.

Nonplatinum Topotecan Combinations Versus Topotecan Alone for Recurrent Ovarian Cancer: Results of a Phase III Study of the North-Eastern German Society of Gynecological Oncology Ovarian Cancer Study Group

2008 ◽  
Vol 26 (19) ◽  
pp. 3176-3182 ◽  
Author(s):  
Jalid Sehouli ◽  
Dirk Stengel ◽  
Guelten Oskay-Oezcelik ◽  
Alain G. Zeimet ◽  
Harald Sommer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Refractory

PurposeThe management of recurrent ovarian cancer remains controversial. Single-agent topotecan is an established treatment option, and preliminary evidence suggests improved tumor control by combining topotecan with etoposide or gemcitabine.Patients and MethodsWomen with relapsed ovarian cancer after primary surgery and platinum-based chemotherapy were randomly assigned to topotecan monotherapy 1.25 mg/m2/d, topotecan 1.0 mg/m2plus oral etoposide 50 mg/d, or topotecan 0.5 mg/m2/d plus gemcitabine 800 mg/m2on day 1 and 600 mg/m2on day 8 every 3 weeks. Patients were stratified for platinum-refractory and platinum-sensitive disease according to a recurrence-free interval of less or more than 12 months, respectively. The primary end point was overall survival. Secondary end points included progression-free survival, objective response rates, toxicity, and quality of life (as measured by the European Organisation for Research and Treatment of Cancer [EORTC] 30-item Quality-of-Life Questionnaire).ResultsThe trial enrolled 502 patients with a mean age of 60.5 years (± 10.2 years), 208 of whom were platinum resistant. Median overall survival was 17.2 months (95% CI, 13.5 to 21.9 months) with topotecan, 17.8 months (95% CI, 13.7 to 20.0 months) with topotecan plus etoposide (log-rank P = .7647), and 15.2 months (95% CI, 11.3 to 20.9 months) with topotecan plus gemcitabine (log-rank P = .2344). Platinum-sensitive patients lived significantly longer than platinum-refractory patients (21.9 v 10.6 months). The median progression-free survival was 7.0, 7.8, and 6.3 months, respectively. Objective response rates were 27.8%, 36.1%, and 31.6%, respectively. Patients under combined treatment were at higher risk of severe thrombocytopenia.ConclusionNonplatinum topotecan combinations do not provide a survival advantage over topotecan alone in women with relapsed ovarian cancer.

Combination therapy with gemcitabine and carboplatin in recurrent ovarian cancer

2005 ◽  
Vol 15 (Suppl 1) ◽  
pp. 36-41 ◽  
Author(s):  
J. Pfisterer ◽  
I. Vergote ◽  
A. Du Bois ◽  
E. Eisenhauer
Keyword(s):  
Ovarian Cancer ◽  
Gynecologic Cancer ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Initial Therapy ◽  
Primary Objective ◽  
Platinum Sensitive ◽  
Abdominal Symptoms ◽  
Global Quality Of Life

Many patients with advanced ovarian cancer will develop recurrent disease. For those patients who have recurrence of disease at least 6 months after initial therapy, the paclitaxel–platinum combination has been shown to be a superior treatment to platinum monotherapy. However, many patients develop clinically relevant neurotoxicity, frequently resulting in treatment discontinuation. The efficacy and safety of an alternative regimen that does not show significant neurotoxicity were evaluated by comparing gemcitabine–carboplatin with carboplatin in platinum-sensitive recurrent ovarian cancer patients in a Gynecologic Cancer InterGroup trial of the Arbeitsgemeinschaft Gynakologische Onkologie Ovarian Cancer Study Group, the National Cancer Institute of Canada Clinical Trials Group, and the European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group. Participants with recurrent platinum-sensitive ovarian cancer were randomly assigned to receive either gemcitabine–carboplatin or carboplatin every 21 days. The primary objective was to compare progression-free survival (PFS) between the groups. From September 1999 to April 2002, 356 patients (178 participants received gemcitabine–carboplatin, 178 received carboplatin only) were randomized to treatment. Patients received six cycles of either gemcitabine–carboplatin or carboplatin. With a median follow-up of 17 months, median PFS was 8.6 months for gemcitabine–carboplatin (95% confidence interval [CI] 7.9–9.7 months) and 5.8 months for carboplatin (95% CI 5.2–7.1 months; hazard ratio [HR] 0.72 [95% CI 0.58–0.90; P = 0.0032]). The response rate for the gemcitabine–carboplatin group was 47.2% (95% CI 39.9–54.5%) and 30.9% for carboplatin group (95% CI 24.1–37.7%; P = 0.0016). The HR for overall survival was 0.96 (95% CI 0.75–1.23; P = 0.7349). Patients treated with gemcitabine–carboplatin reported significantly faster palliation of abdominal symptoms and a significantly improved global quality of life. Gemcitabine–carboplatin treatment significantly improves the PFS of patients with platinum-sensitive recurrent ovarian cancer.

Volasertib Versus Chemotherapy in Platinum-Resistant or -Refractory Ovarian Cancer: A Randomized Phase II Groupe des Investigateurs Nationaux pour l'Etude des Cancers de l'Ovaire Study

2016 ◽  
Vol 34 (7) ◽  
pp. 706-713 ◽  
Author(s):  
Eric Pujade-Lauraine ◽  
Frédéric Selle ◽  
Béatrice Weber ◽  
Isabelle-Laure Ray-Coquard ◽  
Ignace Vergote ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Disease Control ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Platinum Resistant ◽  
Grade 3

Purpose Volasertib is a potent and selective cell-cycle kinase inhibitor that induces mitotic arrest and apoptosis by targeting Polo-like kinase. This phase II trial evaluated volasertib or single-agent chemotherapy in patients with platinum-resistant or -refractory ovarian cancer who experienced failure after treatment with two or three therapy lines. Patients and Methods Patients were randomly assigned to receive either volasertib 300 mg by intravenous infusion every 3 weeks or an investigator’s choice of single-agent, nonplatinum, cytotoxic chemotherapy. The primary end point was 24-week disease control rate. Secondary end points included best overall response, progression-free survival (PFS), safety, quality of life, and exploratory biomarker analyses. Results Of the 109 patients receiving treatment, 54 received volasertib and 55 received chemotherapy; demographics were well balanced. The 24-week disease control rates for volasertib and chemotherapy were 30.6% (95% CI, 18.0% to 43.2%) and 43.1% (95% CI, 29.6% to 56.7%), respectively, with partial responses in seven (13.0%) and eight (14.5%) patients, respectively. Median PFS was 13.1 weeks and 20.6 weeks for volasertib and chemotherapy (hazard ratio, 1.01; 95% CI, 0.66 to 1.53). Six patients (11%) receiving volasertib achieved PFS fore more than 1 year, whereas no patient receiving chemotherapy achieved PFS greater than 1 year. No relationship between the expression of the biomarkers tested and their response was determined. Patients treated with volasertib experienced more grade 3 and 4 drug-related hematologic adverse events (AEs) and fewer nonhematologic AEs than did patients receiving chemotherapy. Discontinuation resulting from AEs occurred in seven (13.0%) and 15 (27.3%) patients in the volasertib and chemotherapy arms, respectively. Both arms showed similar effects on quality of life. Conclusion Single-agent volasertib showed antitumor activity in patients with ovarian cancer. AEs in patients receiving volasertib were mainly hematologic and manageable.

Cytoreductive surgery followed by chemotherapy and olaparib maintenance in BRCA 1/2 mutated recurrent ovarian cancer: a retrospective MITO group study

2021 ◽  
pp. ijgc-2020-002343
Author(s):  
Sabrina Chiara Cecere ◽  
Lucia Musacchio ◽  
Michele Bartoletti ◽  
Vanda Salutari ◽  
Laura Arenare ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cytoreductive Surgery ◽  
Response Rate ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Free Interval ◽  
Platinum Based Chemotherapy

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.

Phase II trial of irinotecan plus bevacizumab for heavily pretreated recurrent ovarian cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5016-5016
Author(s):  
Salvia Sanjay Jain ◽  
Yan G. Makeyev ◽  
Franco Muggia ◽  
James L. Speyer ◽  
John Patrick Curtin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Single Agent ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Median Number ◽  
Protocol Amendment ◽  
Platinum Sensitive ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

5016 Background: Irinotecan and bevacizumab have single agent activity in platinum sensitive (PSen) and resistant (PRes) ovarian cancer patients (pts). We sought to evaluate the efficacy and toxicity of irinotecan plus bevacizumab in these pts. The trial was designed to evaluate whether the progression free survival (PFS) at 6 months is at least 40% and with secondary objectives of estimating response rate (RR), duration of response (DoR), time to progression and toxicity. Methods: No limitation on number of prior regimens was placed, and prior use of study drugs was allowed. Irinotecan 250mg/m2 and bevacizumab 15mg/kg every 3 weeks were given. Due to treatment-related grade 3 toxicity (diarrhea and neutropenia) experienced by the first 5 pts on the study, the dose of irinotecan was amended to 175mg/m2. Results: 20 pts with recurrent ovarian cancer [PSen 5, PRes 15] of a planned 35 have been recruited thus far. Median age is 59 (45-78). Median number of prior regimens is 5 (3-12) with 9 pts demonstrating progressive disease (PD) on prior topotecan-containing regimens and 7 pts exhibiting PD on prior bevacizumab-containing regimens. 4 pts discontinued treatment before 2 cycles (2 for protocol defined toxicity, 2 by patient/physician choice). Partial response (PR) was observed in 2 PSen pts and 1 PRes pt, while stable disease (SD)was seen in 9 (2 PSen, 7 PRes) out of the 15 pts assessable for response at this time. 3 pts demonstrated PD after 2 cycles of treatment. 12 of 13 pts with PR or SD by RECIST also had response by CA125 criteria. Median DoR thus far (SD plus PR) is 18 weeks (4-37). 6 pts have ongoing response (4-18 weeks). Of 19 pts that received > 2 cycles, 3 had grade 3 diarrhea (2 before protocol amendment and 1 after). 2 pts had grade 3/4 neutropenia (1 before and 1 after protocol amendment). Median PFS is 9.6 months (mts). Median overall survival is 15.5 mts. PFS rate at 6 mts is 61% with 95% confidence interval: (40%, 92%). Conclusions: Results of the trial to date suggest the hypothesis that the PFS at 6 mts is less than 40% can be rejected. Activity of this regimen is encouraging given the heavily pretreated nature of the pts. Dose-limiting diarrhea and neutropenia required protocol amendment. We continue to accrue study subjects at the amended dosing.

Quality of Life in Platinum-Sensitive Recurrent Ovarian Cancer: Chemotherapy Versus Surgery Plus Chemotherapy

2015 ◽  
Vol 22 (7) ◽  
pp. 2387-2394 ◽  
Author(s):  
Francesco Plotti ◽  
Giuseppe Scaletta ◽  
Alessia Aloisi ◽  
Daniela Luvero ◽  
Stella Capriglione ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Ovarian Cancer ◽  
Cancer Chemotherapy ◽  
Recurrent Ovarian Cancer ◽  
Platinum Sensitive

Phase II Study of Carboplatin and Pemetrexed for the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer

2008 ◽  
Vol 26 (35) ◽  
pp. 5761-5766 ◽  
Author(s):  
Ursula A. Matulonis ◽  
Neil S. Horowitz ◽  
Susana M. Campos ◽  
Hang Lee ◽  
Julie Lee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Fallopian Tube Cancer ◽  
Platinum Sensitive ◽  
Grade 3

Purpose More efficacious, less toxic combinations are needed to treat platinum-sensitive recurrent epithelial ovarian cancer (EOC). Pemetrexed is a multitargeted antifolate with manageable toxicity and has been combined with carboplatin to treat other cancers. Patients and Methods This is a phase II study of carboplatin area under the curve 5 with pemetrexed 500 mg/m2 administered intravenously on day 1 every 21 days for six cycles or for up to eight cycles if clinical benefit occurred. Eligible patients had platinum-sensitive recurrent EOC, peritoneal serous cancer, or fallopian tube cancer. The primary objective was to determine response rate defined by Response Evaluation Criteria in Solid Tumors; other end points included toxicities, progression-free survival (PFS), and overall survival (OS). Results Forty-five patients were accrued; 44 patients received treatment. Overall response rate was 51.1%; there were no complete responses (0%), 23 confirmed partial responses (51.1%), two unconfirmed partial responses (4.4%), 14 patients with stable disease (31.1%), and two patients with progressive disease after two cycles (4.4%). Grade 3 and 4 hematologic toxicities included neutropenia (41%), thrombocytopenia (23%), and anemia (9%); there were no episodes of febrile neutropenia. Grade 3 and 4 nonhematologic toxicities included fatigue (11%), nausea (5%), vomiting (5%), diarrhea (5%), syncope (5%), and pulmonary embolism (5%). Median PFS time was 7.57 months (95% CI, 6.44 to 10.18 months), mean OS time was 20.3 months, and median OS has not yet been reached with a mean follow-up time of 15.3 months. Conclusion Carboplatin/pemetrexed is a well-tolerated regimen with activity in platinum-sensitive recurrent EOC; further testing of this regimen in platinum-sensitive EOC patients is warranted.

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