Gemcitabine and Vinorelbine Combination in Platinum-Sensitive Recurrent Ovarian Cancer

Objectives:Most patients with ovarian cancer are candidates for second-line or salvage treatments often for prolonged periods. Patients with platinum-sensitive disease can benefit from a platinum retreatment with a likelihood of response dependents on the treatment-free interval. Alternative agents and combination chemotherapy are potential therapeutic approaches. At our institution, we carried out a phase II trial to evaluate feasibility, efficacy, and toxicity of gemcitabine and vinorelbine combination in recurrent ovarian carcinoma. The aim of the present study was to evaluate the role of this combination in patients with platinum-sensitive disease.Patients and Methods:Patients with platinum-sensitive disease recurring after 1 or more lines of platinum-based chemotherapy were included. Vinorelbine at 25 mg/m2followed by gemcitabine at 1000 mg/m2was administered intravenously on days 1 and 8 every 3 weeks. Response Evaluation Criteria in Solid Tumors and cancer antigen 125 test (CA-125 Kinetics [Rustin criteria]) were adopted to classify responses. Toxicity was assessed according to the National Cancer Institute Common Toxicity Criteria.Results:Thirty-nine patients were eligible. Platinum-free interval (PFI) was 6 to 12 months in 13 patients (33.3%; PFI 6-12) and more than 12 months in 26 patients (66.7%; PFI > 12). The overall response rate was 48.7%, with 6 complete responses. Median response duration was 38 weeks. The response rate was 23% in PFI 6-12 and 62% in PFI >12. The most frequently observed toxicity was hematological, with 23% of the patients having grade 3 or 4 neutropenia.Conclusions:Gemcitabine and vinorelbine combination is effective and well tolerated in recurrent platinum-sensitive ovarian cancer. It may represent an option in the management of these patients because the chronic nature of the disease.

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Topotecan Has Substantial Antitumor Activity as First-Line Salvage Therapy in Platinum-Sensitive Epithelial Ovarian Carcinoma: A Gynecologic Oncology Group Study

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.5.1062 ◽

2000 ◽

Vol 18 (5) ◽

pp. 1062-1062 ◽

Cited By ~ 165

Author(s):

William P. McGuire ◽

John A. Blessing ◽

Michael A. Bookman ◽

Samuel S. Lentz ◽

Charles J. Dunton

Keyword(s):

Ovarian Cancer ◽

Active Drug ◽

Response Rate ◽

Gynecologic Oncology ◽

Response Duration ◽

Recurrent Ovarian Cancer ◽

Hematologic Toxicity ◽

Gynecologic Oncology Group ◽

Median Response ◽

Platinum Sensitive

PURPOSE: Topotecan is known to be active in recurrent ovarian cancer, but most prior studies have focused on platinum-resistant or refractory populations. This study was undertaken to define the response rate and progression-free interval in platinum-sensitive patients. PATIENTS AND METHODS: Patients with recurrent ovarian cancer after one or two prior chemotherapy regimens and in whom the interval between prior platinum therapy and the initiation of protocol therapy was greater than 6 months were treated with topotecan 1.5 mg/m2 intravenously over 30 minutes daily for 5 days, with this cycle repeated every 21 days. RESULTS: Forty-eight patients were entered onto the study; 47 were assessable for toxicity and 46 for response. The response rate was 33% (two complete responses and 13 partial responses), with a median response duration of 11.2 months. Hematologic toxicity predominated but was manageable in most patients with frequent incorporation of cytokines and RBC and platelet transfusions. Fatigue was reported in 15 patients and resulted in the discontinuation of therapy in five responding patients. CONCLUSION: Topotecan is an active drug in platinum-sensitive ovarian cancer, with significant but manageable hematologic toxicity. Fatigue is also a common problem that may be dose-limiting in some patients.

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

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-002343 ◽

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.

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Phase II study of gemcitabine and oxaliplatin in patients with recurrent ovarian cancer: an Australian and New Zealand Gynaecological Oncology Group study

International Journal of Gynecological Cancer ◽

10.1111/j.1525-1438.2007.00763.x ◽

2007 ◽

Vol 17 (2) ◽

pp. 359-366 ◽

Cited By ~ 15

Author(s):

P. Harnett ◽

M. Buck ◽

P. Beale ◽

A. Goldrick ◽

S. Allan ◽

...

Keyword(s):

Ovarian Cancer ◽

Single Agent ◽

Recurrent Ovarian Cancer ◽

Ca 125 ◽

Platinum Sensitive ◽

Best Response ◽

Platinum Based Chemotherapy ◽

Group A ◽

Intent To Treat ◽

Group B

Gemcitabine and oxaliplatin have shown single-agent activity in relapsed ovarian cancer. This combination was used to determine response rates, time-to-event efficacy measures, and toxicity in patients with recurrent ovarian cancer. Patients with prior platinum-based chemotherapy who had measurable lesions and/or elevated CA-125 levels were identified as group A (platinum-refractory/platinum-resistant patients) and group B (platinum-sensitive patients). All patients received gemcitabine 1000 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every 21 days for up to eight cycles. Seventy-five patients (21 in group A and 54 in group B), with a median age of 58 years (range, 37–78), were enrolled. A median of six cycles (range, 1–8) was administered. By intent-to-treat analysis, 15 patients with measurable disease achieved partial response for an overall best response rate of 20.0% (9.5% in group A and 24.1% in group B). CA-125 response was observed in 48.4% patients (30.0% in group A and 57.1% in group B). Median time to progressive disease was 7.1 months (95% CI, 5.6–9.0 months) with 5.0 months in group A and 8.3 months in group B. Median overall survival was 17.8 months (95% CI, 12.9–21.3 months) with 9.2 months for group A and 20.0 months for group B. Major grade 3/4 toxicities were neutropenia (61.3%), leukopenia (24.0%), nausea (16.0%), and vomiting (22.7%). We conclude that the combination of oxaliplatin and gemcitabine is active in patients with recurrent ovarian cancer, but the regimen is unsatisfactory for further study due to modest response and relatively high toxicity.

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Panitumumab in platinum-sensitive epithelial ovarian cancer patients with KRAS wild-type: The PROVE-study, a phase II randomized multicenter study of the North-Eastern German Society of Gynaecologic Oncology.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5558 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5558-5558 ◽

Cited By ~ 3

Author(s):

Radoslav Chekerov ◽

Peter Klare ◽

Petra Krabisch ◽

Jochem Potenberg ◽

Georg Heinrich ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Progression Free Survival ◽

Recurrent Ovarian Cancer ◽

Ca 125 ◽

Wild Type ◽

Skin Reactions ◽

Free Survival ◽

Platinum Sensitive ◽

Platinum Based Chemotherapy

5558 Background: For ovarian cancer (OC) patients with platinum-sensitive recurrence the addition of new biologic agents to chemotherapy may improve survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). The purpose of this trial was to investigate the therapeutic efficacy of panitumumab in the combination with carboplatin-based chemotherapy in relation to the respective standard combination in patients with a KRAS wildtype with platinum-sensitive recurrent ovarian cancer (NCT01388621). Methods: Major eligibility criteria were pretreated platinum-sensitive epithelial ovarian/ fallopian/ peritoneal cancer and no more than 2 prior treatments for this disease. Only patients with measurable disease or elevated CA125 and with KRAS wild type were eligible. Patients were treated with Carboplatin AUC4/Gemcitabine 1000 mg/m² or Carboplatin AUC5/PLD 40 mg/m² and randomized to panitumumab 6 mg/kg day 1 and day 15, every 3 or 4 weeks. Tumor assessment was performed at baseline and at every third cycle according to CT-scan and CA-125 criteria. Results: In this multi-institutional phase II trial 102 patients were randomized and 96 enrolled for the final analysis. Progression-free survival in the intention-to-treat population (N=96) was 9.5 vs. 10.7 months (HR 0.829, 95%CI of 8.5-11.6 months vs 8.5-13.1 months) for the experimental vs. standard arm, p=0.45. Data of overall survival are not jet evaluable. The most common treatment related grade 3+ toxicities included hematologic toxicity (54%), skin reactions (18%) and gastrointestinal events (16%). Conclusions: The addition of panitumumab to platinum-based chemotherapy for recurrent ovarian cancer does not influence efficacy and progression-free survival in platinum sensitive patients, while no new additional toxicity aspects for panitumumab were evaluated. Clinical trial information: NCT01388621.

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Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer and a time-to-progression after penultimate platinum-based chemotherapy of 6-12 or >12 months: a subgroup analysis of the phase III NORA trial

Gynecologic Oncology ◽

10.1016/s0090-8258(21)00681-8 ◽

2021 ◽

Vol 162 ◽

pp. S18

Author(s):

Qidan Huang ◽

Xiaohua Wu ◽

Jianqing Zhu ◽

Danqing Wang ◽

Jiaxin Yang ◽

...

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Subgroup Analysis ◽

Recurrent Ovarian Cancer ◽

Phase Iii ◽

Time To Progression ◽

Platinum Sensitive ◽

Platinum Based Chemotherapy

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Maintenance with Trabectedin in the Treatment of Platinum-Sensitive Recurrent Ovarian Cancer

Case Reports in Oncology ◽

10.1159/000500411 ◽

2019 ◽

Vol 12 (2) ◽

pp. 447-455 ◽

Cited By ~ 1

Author(s):

Eva María Guerra Alía ◽

Cayetano Sempere Ortega ◽

Alfonso Cortés Salgado ◽

Concepción Sanchez Martínez ◽

Julio Galindo Álvarez ◽

...

Keyword(s):

Ovarian Cancer ◽

Pegylated Liposomal Doxorubicin ◽

Abdominal Distension ◽

Recurrent Ovarian Cancer ◽

Response To Treatment ◽

Case Presentation ◽

Good Tolerance ◽

Platinum Sensitive ◽

Platinum Based Chemotherapy ◽

Selection Of

Ovarian cancer is the seventh most common type of cancer and the fifth leading cause of cancer death among women worldwide. The current usual therapeutic approach in this disease includes optimal cytoreductive therapy followed by platinum-based adjuvant chemotherapy, along with neoadjuvant chemotherapy prior to surgery in selected cases. The platinum-free interval (PFI) continues to be the most useful tool to assist in the selection of the subsequent therapy and to predict response to treatment. The combination of trabectedin and pegylated liposomal doxorubicin (PLD) is useful in patients with partially platinum-sensitive recurrent ovarian cancer, in patients who have previously received two or more platinum-based chemotherapy regimens, in patients who have already experienced a platinum-induced hypersensitivity reaction and in patients who have previously failed to respond to a platinum-based treatment. Case Presentation: A 64-years-old postmenopausal woman with pain, abdominal distension, and an altered intestinal transit and with partially platinum-sensitive recurrent ovarian cancer, was successfully treated with a second line of trabectedin chemotherapy in combination with PLD, followed by trabectedin in monotherapy. This case proves the effectiveness of the combination of trabectedin and PLD and demonstrates how the administration of trabectedin, even in monotherapy, allows to maintain an adequate clinical response with good tolerance to the treatment during more than two years of drug administration.

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Activity and Pharmacodynamics of 21-Day Topotecan Infusion in Patients With Ovarian Cancer Previously Treated With Platinum-Based Chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.8.2553 ◽

1999 ◽

Vol 17 (8) ◽

pp. 2553-2553 ◽

Cited By ~ 67

Author(s):

Howard Hochster ◽

Scott Wadler ◽

Carolyn Runowicz ◽

Leonard Liebes ◽

Henry Cohen ◽

...

Keyword(s):

Ovarian Cancer ◽

Mononuclear Cells ◽

Response Rate ◽

Objective Response ◽

Ca 125 ◽

Blood Levels ◽

Time To Progression ◽

Peripheral Blood Mononuclear ◽

Platinum Based Chemotherapy ◽

Previously Treated

PURPOSE: Twenty-one–day topotecan infusion was administered as second-line therapy in patients with previously treated ovarian cancer (based on our prior favorable phase I experience) to determine its activity, time to progression, and pharmacodynamics. PATIENTS AND METHODS: Ovarian cancer patients with measurable lesions and one prior platinum-containing regimen were eligible. Topotecan 0.4 mg/m2/d 21-day continuous ambulatory intravenous infusion, with appropriate dose modifications for toxicity, was administered every 28 days. Weekly blood levels of topotecan and topoisomerase-1 (topo-1) levels in peripheral-blood mononuclear cells (PBMCs) were determined for pharmacodynamic correlation. RESULTS: Twenty-four patients were entered onto the study (six cisplatin-refractory, five relapsing within < 6 months and 13 relapsing > 6 months after platinum-based therapy). A total of 128 cycles of topotecan (median, four cycles per patient; range, one to 12 cycles) were administered. The major toxicity was neutropenia (29% grade 3 in all cycles and 4% grade 4). One episode of grade 4 thrombocytopenia (4%) occurred. Fifty-two percent of the patients had anemia that required transfusions. Eight of 23 patients with measurable disease (35%; 95% confidence interval [CI], 15% to 54%) had partial responses (PRs) lasting longer than 1 month. Two of these patients had minor residual computed tomographic changes but had clinical complete remissions that lasted up to 53 weeks while they were not undergoing further therapy. One patient with nonmeasurable disease had a PR (by CA-125 criteria) that lasted 6 months, for an overall response rate of 38% in nine of 24 patients (95% CI, 18% to 57%). The median time to progression was 26 weeks. Pharmacodynamic analysis demonstrated a statistically significant decrease in free PBMC topo-1 level at weeks 2 and 3 of drug administration. There was a strong statistical correlation between the decrease in free topo-1 levels and increasing area under the curve (AUC) for topotecan. This was confirmed in a pharmacodynamic model. CONCLUSION: Twenty-one–day infusion is a well-tolerated method of administering topotecan. Pharmacodynamic studies demonstrate correlations between (1) the week of infusion and the PBMC topo-1 level, (2) the AUC of topotecan and the decrease in topo-1 levels, and (3) the change in topo-1 level and the neutrophil nadir. The objective response rate of 35% to 38% (95% CI, 15% to 57%) in this small multicenter study is at the upper level for topotecan therapy in previously treated ovarian cancer. Prolonged topotecan administration therefore warrants further investigation in larger, randomized studies comparing this 21-day schedule with the once-daily-for-5-days schedule.

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Fifth Alon Dembo Memorial Workshop: Case 3

International Journal of Gynecological Cancer ◽

10.1111/igc.0b013e3181f60ad0 ◽

2010 ◽

Vol 20 (Suppl 2) ◽

pp. S24-S26 ◽

Cited By ~ 1

Author(s):

Peter E. Schwartz

Keyword(s):

Ovarian Cancer ◽

Ovarian Cancer Patient ◽

Recurrent Ovarian Cancer ◽

Ca 125 ◽

Advanced Stage ◽

Recurrent Cancer ◽

Treatment Regimens ◽

Platinum Sensitive ◽

Very High

Background:OVO5/EORTC 55855, a study punitively refuting the value of CA-125 in the follow-up of ovarian cancer patients, has many deficiencies, including a heterogeneous ovarian cancer patient population, no control of initial treatment regimens, and no control of subsequent surgery or chemotherapeutic management for recurrence. Recent studies suggest a role for prompt surgery in selected cases of recurrent ovarian cancer with CA-125 elevations, a role for tamoxifen in managing rising CA-125 levels in patients without evidence of disease and the use of platinum doublets for treating recurrent platinum-sensitive disease, none of which were incorporated into OVo5/EORTC 55955.Case:A patient with advanced stage ovarian cancer presenting with a CA-125 level of 2000 U/mL, who is initially treated with surgery followed by chemotherapy and has a normal CT scan and normal CA-125 at completion of her initial chemotherapy.Conclusion:This patient remains at a very high risk for recurrence. I would continue to monitor this patient with serial CA-125 levels to identify recurrent cancer and consider initiating treatment before it is clinically obvious.

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Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2009.25.4037 ◽

2010 ◽

Vol 28 (19) ◽

pp. 3107-3114 ◽

Cited By ~ 270

Author(s):

Bradley J. Monk ◽

Thomas J. Herzog ◽

Stanley B. Kaye ◽

Carolyn N. Krasner ◽

Jan B. Vermorken ◽

...

Keyword(s):

Ovarian Cancer ◽

Liposomal Doxorubicin ◽

Performance Status ◽

Pegylated Liposomal Doxorubicin ◽

Progression Free Survival ◽

Recurrent Ovarian Cancer ◽

Hazard Ratio ◽

Platinum Sensitive ◽

Platinum Based Chemotherapy ◽

Hand Foot Syndrome

PurposeThe objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy.Patients and MethodsWomen ≥ 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m2followed by a 3-hour infusion of trabectedin 1.1 mg/m2every 3 weeks or PLD 50 mg/m2every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment.ResultsPatients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (ORR) was 27.6% for trabectedin/PLD v 18.8% for PLD (P = .0080); for platinum-sensitive patients, it was 35.3% v 22.6% (P = .0042), respectively. ORR, PFS, and overall survival among platinum-resistant patients were not statistically different. Neutropenia was more common with trabectedin/PLD. Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative. Hand-foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone.ConclusionWhen combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.

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