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.

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.

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 Cost Effectiveness of Intraperitoneal Compared With Intravenous Chemotherapy for Women With Optimally Resected Stage III Ovarian Cancer: A Gynecologic Oncology Group Study

2008 ◽  
Vol 26 (25) ◽  
pp. 4144-4150 ◽  
Author(s):  
Laura J. Havrilesky ◽  
Angeles Alvarez Secord ◽  
Kathleen M. Darcy ◽  
Deborah K. Armstrong ◽  
Shalini Kulasingam
Keyword(s):  
Ovarian Cancer ◽  
Cost Effectiveness ◽  
Time Horizon ◽  
Gynecologic Oncology ◽  
Cost Effective ◽  
Stage Iii ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Resected Stage ◽  
The Cost

Purpose To determine the cost effectiveness of intraperitoneal versus intravenous regimens for adjuvant treatment of optimally resected stage III ovarian cancer. Patients and Methods A decision model was developed to compare the cost effectiveness at 7-, 11.5-, and 35-year horizons of intravenous carboplatin and paclitaxel (IV-CARBO/PAC), intravenous cisplatin and paclitaxel (IV-CIS/PAC), or intravenous paclitaxel followed by intraperitoneal cisplatin and paclitaxel (IP-CIS/PAC). Survival data were from women participating in representative Gynecologic Oncology Group (GOG) protocols. Medicare reimbursement rates and the Agency for Healthcare Research and Quality Database were used to estimate costs for treatment regimens and grade 3 to 4 adverse effects, respectively. Results Median predicted survival was 66, 57, 51, and 48 months for IP-CIS/PAC, IV-CARBO/PAC, IV-CIS/PAC (GOG 172), or IV-CIS/PAC (GOG 158), respectively. Across a range of analyses, IV-CIS/PAC was more costly and had lower life expectancy than IV-CARBO/PAC. Compared with IV-CARBO/PAC, IP-CIS/PAC had an incremental cost-effectiveness ratio (ICER) of $180,022 per quality-adjusted life year (QALY) saved at a 7-year time horizon, $71,835/QALY at 11.5 years, and $32,053/QALY over a lifetime. Extending the survival advantage of IP-CIS/PAC over 11.5 years and a lifetime results in ICERs of $26,249 and $23,973, respectively. Assuming IP-CIS/PAC and IV-CIS/PAC were equally effective when administered on an outpatient basis, the ICER of IP-CIS/PAC compared with IV-CARBO/PAC was $26,311. Conclusion Inpatient IP-CIS/PAC, while not cost effective compared with IV-CARBO/PAC at 7 years, becomes cost effective if a longer time horizon is modeled and/or a survival benefit can be assumed to persist longer than currently available data. Outpatient IP-CIS/PAC may also be cost effective compared with IV-CARBO/PAC if proven as effective as inpatient IP-CIS/PAC.

Principles and practice of intraperitoneal chemotherapy for ovarian cancer

2007 ◽  
Vol 17 (1) ◽  
pp. 1-20 ◽  
Author(s):  
K. Fujiwara ◽  
D. Armstrong ◽  
M. Morgan ◽  
M. Markman
Keyword(s):  
Ovarian Cancer ◽  
Survival Benefit ◽  
Meta Analysis ◽  
Gynecologic Oncology ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
Clinical Aspects ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Phase Iii Trials

Intraperitoneal (IP) chemotherapy has been studied for years to improve the survival of patients with ovarian cancer. Recently, the result of Gynecologic Oncology Group 172 trial comparing IP versus intravenous administration of cisplatin-based chemotherapy was published, demonstrating the improvement of survival benefit in favor of the IP arm. This trial is the third trial that showed a survival benefit on IP chemotherapy. The National Cancer Institute (NCI) and Gynecologic Oncology Group have done a meta-analysis on the results of these three US trials and other phase III trials of IP versus intravenous chemotherapy, and significant improvement of survival was shown with IP therapy. Based on this meta-analysis, NCI has released a clinical announcement encouraging the gynecological oncology community to consider IP chemotherapy as the standard treatment for optimally debulked advanced ovarian cancer patients. However, there still are controversial issues regarding the use of IP chemotherapy. It is important to understand how IP chemotherapy works to solve those issues in the future. In this review article, we discuss the principles and clinical aspects of IP chemotherapy and also discuss the current problems and future perspectives in IP chemotherapy

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 Carboplatin Plus Paclitaxel With or Without Gemcitabine in First-Line Treatment of Epithelial Ovarian Cancer

2010 ◽  
Vol 28 (27) ◽  
pp. 4162-4169 ◽  
Author(s):  
Andreas du Bois ◽  
Jørn Herrstedt ◽  
Anne-Claire Hardy-Bessard ◽  
Hans-Helge Müller ◽  
Philipp Harter ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Objective Response ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Term Survival ◽  
Advanced Epithelial Ovarian Cancer

PurposeOne attempt to improve long-term survival in patients with advanced ovarian cancer was thought to be the addition of more non–cross-resistant drugs to platinum-paclitaxel combination regimens. Gemcitabine was among the candidates for a third drug.Patients and MethodsWe performed a prospective, randomized, phase III, intergroup trial to compare carboplatin plus paclitaxel (TC; area under the curve [AUC] 5 and 175 mg/m2, respectively) with the same combination and additional gemcitabine 800 mg/m2on days 1 and 8 (TCG) in previously untreated patients with advanced epithelial ovarian cancer. TC was administered intravenously (IV) on day 1 every 21 days for a planned minimum of six courses. Gemcitabine was administered by IV on days 1 and 8 of each cycle in the TCG arm.ResultsBetween 2002 and 2004, 1,742 patients were randomly assigned; 882 and 860 patients received TC and TCG, respectively. Grades 3 to 4 hematologic toxicity and fatigue occurred more frequently in the TCG arm. Accordingly, quality-of-life analysis during chemotherapy showed a disadvantage in the TCG arm. Although objective response was slightly higher in the TCG arm, this did not translate into improved progression-free survival (PFS) or overall survival (OS). Median PFS was 17.8 months for the TCG arm and 19.3 months for the TC arm (hazard ratio [HR], 1.18; 95% CI, 1.06 to 1.32; P = .0044). Median OS was 49.5 for the TCG arm and 51.5 months for the TC arm (HR, 1.05; 95% CI, 0.91 to 1.20; P = .5106).ConclusionThe addition of gemcitabine to carboplatin plus paclitaxel increased treatment burden, reduced PFS time, and did not improve OS in patients with advanced epithelial ovarian cancer. Therefore, we recommend no additional clinical use of TCG in this population.

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.

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