scholarly journals Bevacizumab use in the frontline, maintenance and recurrent settings for ovarian cancer

2020 ◽  
Vol 16 (7) ◽  
pp. 225-246 ◽  
Author(s):  
Carolyn E Haunschild ◽  
Krishnansu S Tewari
Keyword(s):  
Ovarian Cancer ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Double Blind ◽  
Free Survival ◽  
Platinum Sensitive ◽  
The Us ◽  
Us Fda

On 13 June 2018, Genentech, Inc. issued a press release announcing that the US FDA had approved the antiangiogenesis drug, bevacizumab, in combination with chemotherapy for frontline and maintenance therapy for women with newly diagnosed ovarian cancer. Regulatory approval was based on the National Cancer Institute-sponsored Gynecologic Oncology Group (GOG) protocol 0218, the Phase III, randomized, placebo-controlled, double-blind, multi-center and multi-national clinical trial that met its primary end point, progression-free survival. Bevacizumab is now approved in the frontline, platinum-sensitive recurrent and platinum-resistant recurrent settings for epithelial ovarian cancer. This review will address the broad range of clinical trials addressing the efficacy of bevacizumab use in ovarian cancer.

scholarly journals Counterpoint: Intraperitoneal Chemotherapy: An Investigational Treatment in Ovarian Cancer

2004 ◽  
Vol 2 (6) ◽  
pp. 555-560 ◽  
Author(s):  
Robert F. Ozols
Keyword(s):  
Ovarian Cancer ◽  
Standard Therapy ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Systemic Circulation ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Phase Ii Trials

Intraperitoneal (IP) chemotherapy in ovarian cancer has been studied since 1978. Numerous phase II trials have been performed, which have shown that higher levels can be obtained in the peritoneal cavity compared with systemic circulation after administration of cytoxic agents in a large volume via a semi-permanent catheter. Three randomized trials have been performed in patients with ovarian cancer comparing different IP regimens to standard therapy with intravenous agents. The last two trials from the Gynecologic Oncology Group (GOG) and the Southwest Oncology Group (SWOG) compared two different IP regimens versus standard therapy with intravenous cisplatin plus paclitaxel. Although an improvement in progression-free survival was reported for the IP regimens, they have been associated with unacceptable toxicity, and no IP regimen can be considered standard therapy. Maintenance therapy with IP cisplatin also failed to improve survival in patients who obtained complete remission after intravenous chemotherapy. The GOG is considering another phase III trial of IP therapy that will compare a carboplatin-based regimen versus standard therapy with intravenous paclitaxel plus carboplatin. Unless such a trial shows an improvement in clinical outcome, intravenous carboplatin plus paclitaxel remains the standard of care and IP chemotherapy should not be used outside of a clinical trial.

Phase III Trial of Ifosfamide With or Without Paclitaxel in Advanced Uterine Carcinosarcoma: A Gynecologic Oncology Group Study

2007 ◽  
Vol 25 (5) ◽  
pp. 526-531 ◽  
Author(s):  
Howard D. Homesley ◽  
Virginia Filiaci ◽  
Maurie Markman ◽  
Pincas Bitterman ◽  
Lynne Eaton ◽  
...  
Keyword(s):  
Performance Status ◽  
Gynecologic Oncology ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Uterine Carcinosarcoma ◽  
New Agents ◽  
Phase Iii Trial ◽  
Free Survival

Purpose To determine if paclitaxel added to ifosfamide as first-line treatment for advanced uterine carcinosarcoma (CS) improves overall survival (OS), progression-free survival (PFS), response, and toxicity. Patients and Methods Eligible patients had measurable stage III or IV, persistent, or recurrent uterine CS. Random assignment to treatment was between ifosfamide 2.0 g/m2 intravenously (IV) daily for 3 days (arm 1) or ifosfamide 1.6 g/m2 IV daily for 3 days plus paclitaxel 135 mg/m2 by 3-hour infusion day 1 (arm 2). Mesna was administered similarly (both arms); filgrastim began on day 4 (arm 2). Cycles were repeated every 21 days up to eight cycles. Results Of 214 patients enrolled, 179 were eligible (arm 1, 91 patients; arm 2, 88 patients). Arm 2 patients experienced more frequent and severe sensory neuropathy (grade 1 to 4; 8% v 30%). The crude response rate was 29% (arm 1) and 45% (arm 2). The odds of response stratified by performance status were 2.21 greater in arm 2 (P = .017). Median PFS and OS, respectively, for arm 1 compared with arm 2 were 3.6 v 5.8 months and 8.4 v 13.5 months, respectively. There was a 31% decrease in the hazard of death (hazard ratio [HR], 0.69; 95% CI, 0.49 to 0.97; P = .03) and a 29% decrease in the hazard of progression (HR, 0.71; 95% CI, 0.51 to 0.97; P = .03) relative to arm 1 when stratifying by performance status. Conclusion OS was significantly improved in arm 2, and toxicities were as expected and manageable. However, the need for active new agents persists, given that OS remains relatively poor in this disease.

Phase III Randomized Study of Cisplatin Versus Paclitaxel Versus Cisplatin and Paclitaxel in Patients With Suboptimal Stage III or IV Ovarian Cancer: A Gynecologic Oncology Group Study

2000 ◽  
Vol 18 (1) ◽  
pp. 106-106 ◽  
Author(s):  
Franco M. Muggia ◽  
Patricia S. Braly ◽  
Mark F. Brady ◽  
Gregory Sutton ◽  
Theodore H. Niemann ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Combination Therapy ◽  
Death Rate ◽  
Gynecologic Oncology ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Treatment Groups

PURPOSE: To assess progression-free survival (PFS) and overall survival (OS) in patients with suboptimally debulked epithelial ovarian cancer receiving cisplatin (100 mg/m2) or 24-hour infusion paclitaxel (200 mg/m2) or the combination of paclitaxel (135 mg/m2) followed by cisplatin (75 mg/m2). PATIENTS AND METHODS: After stratification for disease measurability, patients were randomized to receive six cycles of one of the treatments every 3 weeks. If measurable, complete response (CR) or partial response (PR) was determined. RESULTS: Six hundred fourteen of 648 patients who entered onto the trial were eligible. Monotherapies were discontinued more frequently (cisplatin because of toxicity or patient refusal [17%], and paclitaxel because of progression [20%]) compared with the combination therapy (7% and 6%, respectively). Neutropenia, fever, and alopecia were more severe with paclitaxel-containing regimens; whereas anemia, thrombocytopenia, neurotoxicity, nephrotoxicity, and gastrointestinal toxicity were more severe with cisplatin-containing regimens. The CR/PR rates on paclitaxel monotherapy were significantly lower compared with the cisplatin regimens (42% v 67%, respectively; P < .001). The relative hazard (RH) of first progression or death was significantly greater among those randomized to paclitaxel (RH = 1.41; 95% confidence interval [CI], 1.15 to 1.73; P < .001) when compared with cisplatin; however, RH did not differ significantly between the two cisplatin regimens (RH = 1.06; 95% CI, 0.895 to 1.30). Relative to cisplatin, the death rate on paclitaxel was 15% greater (RH = 1.15; 95% CI, 0.929 to 1.42), and the death rate on the combination treatment was 1% less (RH = 0.99; 95% CI, 0.795 to 1.23). These differences among treatment groups were not statistically significant (P = .31). CONCLUSION: Cisplatin alone or in combination yielded superior response rates and PFS relative to paclitaxel. However, OS was similar in all three arms, and the combination therapy had a better toxicity profile. Therefore, the combination of cisplatin and paclitaxel remains the preferred initial treatment option.

Consolidation therapy revisited: intravenous chemotherapy

2003 ◽  
Vol 13 (Suppl 2) ◽  
pp. 204-207 ◽  
Author(s):  
M. Markman
Keyword(s):  
Ovarian Cancer ◽  
Gynecologic Oncology ◽  
Single Agent ◽  
Progression Free Survival ◽  
Gynecologic Oncology Group ◽  
Consolidation Therapy ◽  
Oncology Group ◽  
Intravenous Chemotherapy ◽  
Free Survival ◽  
Cumulative Toxicity

The administration of ‘consolidation’ therapy is designed to maximize the benefits achieved from primary chemotherapy, to both improve progression-free and overall survival. Paclitaxel is an excellent agent to consider for a consolidation strategy in ovarian cancer, based on its activity in the disease, its cycle-specificity, and the lack of serious cumulative toxicity (except for neuropathy). A recently reported randomized trial conducted by the South-west Oncology Group and the Gynecologic Oncology Group revealed that 12-monthly cycles of single-agent paclitaxel (175 mg/m2 over 3 h) improves progression-free survival (PFS), compared to 3-monthly cycles of the agent (median PFS: 28 months versus 21 months, P = 0.0023, and hazard ratio 2.31). Further exploration of consolidation/maintenance therapy in the management of ovarian cancer is indicated, focusing on agents that are easy to administer (eg, oral) and that result in limited cumulative toxicity.

Phase III Randomized Trial of Intravenous Cisplatin Plus a 24- or 96-Hour Infusion of Paclitaxel in Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

2007 ◽  
Vol 25 (28) ◽  
pp. 4466-4471 ◽  
Author(s):  
David R. Spriggs ◽  
Mark F. Brady ◽  
Luis Vaccarello ◽  
Daniel L. Clarke-Pearson ◽  
Robert A. Burger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Peritoneal Cancer ◽  
Results Of Treatment ◽  
Grade 3 ◽  
To Receive

Purpose This study was undertaken to assess if prolonged paclitaxel administration in combination with cisplatin improves overall survival (OS) in epithelial ovarian cancer (EOC). Patients and Methods Eligible patients with suboptimal stage III or IV EOC, fallopian tube, or primary peritoneal cancer were randomly allocated to receive six cycles of cisplatin 75 mg/m2 and either paclitaxel 135 mg/m2 during 24 hours (arm 1) or paclitaxel 120 mg/m2 during 96 hours (arm 2). Results Planned accrual was 324 patients; 293 were enrolled before the study was closed as a result of a scheduled interim futility analysis. There were 13 ineligible patients; thus, 140 patients in each arm were assessable. In arm 1, 80% of patients completed all six cycles compared with 83% of patients in arm 2. Grade 4 granulocytopenia was more common in arm 1 (79% v 54%; P < .001) whereas grade 3 or worse anemia was more severe in arm 2 (6% v 18%; P < .003). The median progression-free survival was 1.03 years for arm 1 versus 1.05 years for arm 2. The median OS was 2.49 and 2.54 years for arms 1 and 2, respectively. There have been 237 reported deaths. The relative death rate was approximately 12% greater in arm 2 (hazard ratio, 1.12; 95% CI, 0.860 to 1.45). Conclusion Patients with advanced EOC have a relatively poor prognosis. The results of treatment with cisplatin and paclitaxel are not significantly improved by prolonging the paclitaxel infusion from 24 to 96 hours.

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