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.

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 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.

Phase III Trial of Carboplatin and Paclitaxel Compared With Cisplatin and Paclitaxel in Patients With Optimally Resected Stage III Ovarian Cancer: A Gynecologic Oncology Group Study

2003 ◽  
Vol 21 (17) ◽  
pp. 3194-3200 ◽  
Author(s):  
Robert F. Ozols ◽  
Brian N. Bundy ◽  
Benjamin E. Greer ◽  
Jeffrey M. Fowler ◽  
Daniel Clarke-Pearson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gynecologic Oncology ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Combination Regimen ◽  
Gynecologic Oncology Group ◽  
Resected Stage

Purpose: In randomized trials the combination of cisplatin and paclitaxel was superior to cisplatin and cyclophosphamide in advanced-stage epithelial ovarian cancer. Although in nonrandomized trials, carboplatin and paclitaxel was a less toxic and highly active combination regimen, there remained concern regarding its efficacy in patients with small-volume, resected, stage III disease. Thus, we conducted a noninferiority trial of cisplatin and paclitaxel versus carboplatin and paclitaxel in this population. Patients and Methods: Patients with advanced ovarian cancer and no residual mass greater than 1.0 cm after surgery were randomly assigned to receive cisplatin 75 mg/m2 plus a 24-hour infusion of paclitaxel 135 mg/m2 (arm I), or carboplatin area under the curve 7.5 intravenously plus paclitaxel 175 mg/m2 over 3 hours (arm II). Results: Seven hundred ninety-two eligible patients were enrolled onto the study. Prognostic factors were similar in the two treatment groups. Gastrointestinal, renal, and metabolic toxicity, as well as grade 4 leukopenia, were significantly more frequent in arm I. Grade 2 or greater thrombocytopenia was more common in arm II. Neurologic toxicity was similar in both regimens. Median progression-free survival and overall survival were 19.4 and 48.7 months, respectively, for arm I compared with 20.7 and 57.4 months, respectively, for arm II. The relative risk (RR) of progression for the carboplatin plus paclitaxel group was 0.88 (95% confidence interval [CI], 0.75 to 1.03) and the RR of death was 0.84 (95% CI, 0.70 to 1.02). Conclusion: In patients with advanced ovarian cancer, a chemotherapy regimen consisting of carboplatin plus paclitaxel results in less toxicity, is easier to administer, and is not inferior, when compared with cisplatin plus paclitaxel.

Phase II multicenter open-label study of karenitecin in previously treated epithelial ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study

2008 ◽  
Vol 18 (3) ◽  
pp. 460-464 ◽  
Author(s):  
J. J. KAVANAGH ◽  
M. W. SILL ◽  
P. T. RAMIREZ ◽  
D. WARSHAL ◽  
M. L. PEARL ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Topoisomerase I ◽  
Response Rate ◽  
Gynecologic Oncology ◽  
Complete Response ◽  
Gynecologic Oncology Group ◽  
Open Label ◽  
Peritoneal Cancer ◽  
Previously Treated

The topoisomerase I agents are established as a therapy in recurrent ovarian cancer. Karenitecin, an analog of topotecan with solubility and pharmacologic advantages, was tested in a phase II trial in previously treated patients with recurrent or persistent ovarian cancer. The drug was administered intravenously over 1 h at a dose of 1.0 mg/m2 daily for 5 days every 21 days. Patients were treated until disease progression, intolerable toxicity, or voluntary withdrawal. Response was evaluated according to modified RECIST criteria. Twenty-seven patients were entered into the study. One patient was inevaluable for not receiving any treatment. Of the 26 evaluable patients, there were two partial responses and one complete response for a total response rate of 12%. This response rate was insufficient to justify accrual to the second stage. The most common grade 3 or 4 toxicities were neutropenia (19%) and gastrointestinal (15%). Karenitecin is a well-tolerated topoisomerase compound but has minimal activity in extensively pretreated ovarian cancer with the dose-schedule employed.

Analysis of the cost-effectiveness of paclitaxel as alternative combination therapy for advanced ovarian cancer.

1997 ◽  
Vol 15 (2) ◽  
pp. 640-645 ◽  
Author(s):  
W McGuire ◽  
A I Neugut ◽  
S Arikian ◽  
J Doyle ◽  
C M Dezii
Keyword(s):  
Ovarian Cancer ◽  
Survival Time ◽  
Pharmacoeconomic Analysis ◽  
Gynecologic Oncology ◽  
Alternative Therapy ◽  
Advanced Ovarian Cancer ◽  
Cost Effective ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Kaplan Meier

PURPOSE A phase III trial by the Gynecologic Oncology Group (GOG) provides strong evidence that a new alternative therapy--paclitaxel (Taxol; Bristol-Myers Squibb Co, Princeton, NJ) in combination with cisplatin (Platinol; Bristol-Myers Squibb Co)--is clinically more effective than the standard therapy using cyclophosphamide (Cytoxan; Bristol-Myers Squibb Co) in combination with cisplatin in the treatment of advanced ovarian cancer. We conducted a pharmacoeconomic analysis to determine whether the alternative paclitaxel-cisplatin (TP) therapy is cost-effective (CE) in comparison to standard cyclophosphamide-cisplatin (CP) therapy. METHODS Using an economic model, we applied cost data figures to resource utilization data derived from the two arms of the GOG trial. We examined paclitaxel benefits in terms of increased mean survival time, as well as median survival time. Estimates of the cumulative proportion surviving in the trial were based on Kaplan-Meier procedures. RESULTS Per year of life gained (YLG), TP therapy costs more ($19,820 more for inpatient treatment; $21,222 outpatient) than CP treatment. CONCLUSION The TP regimen's increased mean survival cost per YLG (inpatient and outpatient settings) adds a substantial benefit at an acceptable cost compared with CP therapy.

scholarly journals ASCO Value Framework Highlights the Relative Value of Treatment Options in Ovarian Cancer

2017 ◽  
Vol 13 (12) ◽  
pp. e1030-e1039 ◽  
Author(s):  
Jonathan Foote ◽  
Angeles Alvarez Secord ◽  
Margaret Liang ◽  
David E. Cohn ◽  
Elizabeth Jewell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Clinical Benefit ◽  
Treatment Options ◽  
Gynecologic Oncology ◽  
Additional Cost ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Relative Value ◽  
Dose Dense

Purpose: The ASCO value framework allows physicians and patients to compare the relative value of novel treatments. Our aim was to assess the value of three frontline ovarian cancer therapies by using this framework. Methods: From phase III, randomized controlled clinical trial (RCT) data, the net health benefits (NHBs) for three frontline ovarian cancer treatment options—dose-dense paclitaxel (Japanese Gynecologic Oncology Group study JGOG 3016), intraperitoneal (IP)/intravenous (IV) chemotherapy (Gynecologic Oncology Group [GOG] study GOG 172), and concurrent plus maintenance bevacizumab (GOG 218 and the Seventh International Collaborative Ovarian Neoplasm study [ICON7])—were calculated. The ASCO value framework calculates the NHB by using six criteria: clinical benefit, toxicity, tail of the curve, symptom palliation, treatment-free interval, and quality of life. Clinical benefit calculation uses ASCO-assigned importance weights for overall survival and progression-free survival. The maximum possible NHB points is 180. NHBs were presented alongside the drug-acquisition cost (DAC) of each therapy. A benefit-cost ratio of NHB points per additional cost was calculated. Results: The NHB of dose-dense paclitaxel was 38, at an additional cost of $16 per cycle. IP cisplatin/IV + IP paclitaxel received 29 NHB points, at an additional cost of $1,629 per cycle. Concurrent plus maintenance bevacizumab received 24 NHB points, at an additional cost of $7,581 per cycle (GOG 218) or six NHB points ($3,790 per cycle; ICON7). The ratios of NHB points–to-dollar were as follows: dose-dense paclitaxel, 2.4 (highest); IP chemotherapy, 0.018; and bevacizumab, 0.003 (lowest). Conclusion: Using the ASCO value framework, we constructed value snapshots of three major frontline therapeutic options in ovarian cancer. Dose-dense paclitaxel provided the highest additional value when analysis accounted for NHB and cost. However, additional research is needed to include individual patient preferences and provide personalized value assessments.

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