Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA1-LBA1 ◽  
Author(s):  
R. A. Burger ◽  
M. F. Brady ◽  
M. A. Bookman ◽  
J. L. Walker ◽  
H. D. Homesley ◽  
...  
Keyword(s):  
Residual Disease ◽  
Gynecologic Oncology ◽  
Single Agent ◽  
Stage Iv ◽  
Phase Iii ◽  
Stage Iii ◽  
Gynecologic Oncology Group ◽  
Fallopian Tube Cancer ◽  
Phase Iii Trial ◽  
Grade 3

LBA1 Background: BEV, a humanized anti-VEGF monoclonal antibody, has demonstrated single-agent activity in patients with recurrent EOC, or PPC. The therapeutic impact of concurrent ± maintenance BEV with standard chemotherapy (CT) was evaluated in an international, double-blind, placebo-controlled phase III trial. Methods: Eligible patients had newly diagnosed, previously untreated EOC, PPC or FTC following abdominal surgery for staging and maximal effort at tumor debulking; stage III (macroscopic residual disease) or stage IV disease. The randomly allocated regimens were (1) CT (IV paclitaxel 175 mg/m2 + carboplatin AUC 6 cycles 1-6) + placebo cycles (C)2-22 (R1) (2) CT + concurrent BEV (15 mg/kg) C2-6 + placebo C7-22 (R2) (3) CT + concurrent BEV C2-6 + maintenance BEV C7-22 (R3) Infusions were administered d1 of a 21d cycle. The primary endpoint is progression-free survival (PFS) (radiographic, CA125, clinical criteria or death); secondary endpoints include overall survival, safety, and QoL. Results: 1,873 patients, median age 60, were enrolled from 9/05 - 6/09. Stage III optimally debulked (34%), stage III sub-optimally debulked (40%), and stage IV (26%) patients were similarly distributed in each treatment group. Grade 3 - 4 hypertension was reported in 1.6% (R1), 5.4% (R2), and 10.0% (R3). Grade ≥ 3 GI perforation, hemorrhage or fistula occurred in 0.8% (R1), 2.6% (R2) and 2.3% (R3). Relative to R1, the hazard of first progression or death for R2 was 0.908 (95% CI: 0.795 – 1.04, p=0.16) and for R3 was 0.717 (95% CI: 0.625 – 0.824, p<0.0001). Conclusions: This study demonstrates that front-line treatment of EOC, PPC, and FTC patients with CT plus concurrent and maintenance BEV prolongs PFS. This is the first anti-angiogenic agent to demonstrate benefit in this population. [Table: see text]

Randomized Phase III Trial of Cisplatin With or Without Topotecan in Carcinoma of the Uterine Cervix: A Gynecologic Oncology Group Study

2005 ◽  
Vol 23 (21) ◽  
pp. 4626-4633 ◽  
Author(s):  
Harry J. Long ◽  
Brian N. Bundy ◽  
Edward C. Grendys ◽  
Jo Ann Benda ◽  
D. Scott McMeekin ◽  
...  
Keyword(s):  
Gynecologic Oncology ◽  
Progression Free Survival ◽  
Data Safety Monitoring Board ◽  
Cervix Cancer ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Gynecologic Oncology Group ◽  
Phase Iii Trial ◽  
Grade 3

Purpose On the basis of reported activity of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens. Patients and Methods Eligible patients were randomly allocated to receive cisplatin 50 mg/m2 every 3 weeks (CPT); cisplatin 50 mg/m2 day 1 plus topotecan 0.75 mg/m2 days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m2 day 2, and cisplatin 70 mg/m2 day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately. Results The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27% and 13%, respectively. Conclusion This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.

Phase II trial of intraperitoneal paclitaxel in carcinoma of the ovary, tube, and peritoneum: a Gynecologic Oncology Group Study.

1998 ◽  
Vol 16 (8) ◽  
pp. 2620-2624 ◽  
Author(s):  
M Markman ◽  
M F Brady ◽  
N M Spirtos ◽  
P Hanjani ◽  
S C Rubin
Keyword(s):  
Residual Disease ◽  
Treatment Plan ◽  
Gynecologic Oncology ◽  
Complete Response ◽  
Phase Iii ◽  
Maximum Diameter ◽  
Gynecologic Oncology Group ◽  
Eligibility Criteria ◽  
Grade 3 ◽  
The Impact

PURPOSE To determine the response rate of intraperitoneal (i.p.) paclitaxel in patients with small-volume residual carcinomas of the ovary, fallopian tube, or peritoneum. PATIENTS AND METHODS Eligibility criteria included patients with one of the cancers noted above, with the largest residual disease 0.5 cm or less in maximum diameter at the end of second-look surgery, and prior treatment with systemic paclitaxel was permitted. The treatment plan was paclitaxel 60 mg/m2 i.p. weekly for 16 weeks, followed by surgical evaluation in patients without evidence of disease progression. RESULTS Of 80 patients entered onto the study, 76 were eligible, of whom 86% were considered to be potentially cisplatin-sensitive. Although five patients (7%) did not complete the first course of therapy because of catheter leakage or blockade, 53 patients (70%) received all 16 planned courses. Only 14 patients (18%) received fewer than 11 courses. Treatment was well tolerated, which included only moderate abdominal pain (grade 2, 12 patients; grade 3, one patient) and minimal neutropenia (grade 2, three patients; grade 3, one patient). Of 28 assessable patients with microscopic disease at the start of i.p. therapy, 17 patients (61%) achieved a surgically defined complete response (CR). Only one of 31 patients (3%) with any macroscopic disease achieved a CR. Of the eligible patients, 18 of 76 (24%) achieved a CR. CONCLUSION Salvage i.p. paclitaxel is tolerable and active in patients with microscopic residual disease. The impact of this treatment strategy on survival remains to be assessed in a phase III trial.

Phase III Trial of Doxorubicin With or Without Cisplatin in Advanced Endometrial Carcinoma: A Gynecologic Oncology Group Study

2004 ◽  
Vol 22 (19) ◽  
pp. 3902-3908 ◽  
Author(s):  
J. Tate Thigpen ◽  
Mark F. Brady ◽  
Howard D. Homesley ◽  
John Malfetano ◽  
Brent DuBeshter ◽  
...  
Keyword(s):  
Endometrial Carcinoma ◽  
Response Rate ◽  
Gynecologic Oncology ◽  
Single Agent ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Phase Iii Trials ◽  
Grade 3

Purpose Doxorubicin and cisplatin have activity in endometrial carcinoma and at initiation of this study ranked as the most active agents. This trial of stage III, IV, or recurrent disease evaluated whether combining these agents increases response rate (RR) and prolongs progression-free survival (PFS) and overall survival (OS) over doxorubicin alone. Patients and Methods Of 299 patients registered, 281 (94%) were eligible. Regimens were doxorubicin 60 mg/m2 intravenously or doxorubicin 60 mg/m2 plus cisplatin 50 mg/m2 every 3 weeks until disease progression, unacceptable toxicity, or a total of 500 mg/m2 doxorubicin. Results There were 12 (8%) complete (CR) and 26 (17%) partial responses (PR) among 150 patients receiving doxorubicin versus 25 (19%) CRs and 30 (23%) PRs among patients receiving the combination. The overall response rate was higher among patients receiving the combination (42%) compared with patients receiving doxorubicin (25%; P = .004). Median PFS was 5.7 and 3.8 months, respectively, for the combination and single agent. The PFS hazard ratio was 0.736 (95% CI, 0.577 to 0.939; P = .014). Median OS was 9.0 and 9.2 months, respectively, for the combination and single agent. Overall death rates were similar in the two groups (hazard ratio, 0.928; 95% CI, 0.727 to 1.185). Nausea, vomiting, and hematologic toxicities were common. The combination produced more grade 3 to 4 leukopenia (62% v 40%), thrombocytopenia (14% v 2%), anemia (22% v 4%), and nausea/vomiting (13% v 3%). Conclusion Adding cisplatin to doxorubicin in advanced endometrial carcinoma improves RR and PFS with a negligible impact on OS and produces increased toxicity. These results have served as a building block for subsequent phase III trials in patients with disseminated and high-risk limited endometrial carcinoma.

Carboplatin dosing in the treatment of epithelial ovarian cancer (EOC): A Gynecologic Oncology Group (GOG) study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5041-5041
Author(s):  
Roisin Eilish O'Cearbhaill ◽  
Austin Miller ◽  
Franco Muggia ◽  
Judith A. Smith ◽  
Michael A. Bookman ◽  
...  
Keyword(s):  
Operating Characteristic ◽  
Characteristic Curve ◽  
Gynecologic Oncology ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Predictive Values ◽  
Phase Iii Trial ◽  
Operating Characteristic Curve ◽  
Grade 3 ◽  
The Relationship

5041 Background: Optimal carboplatin dosing (CPRx) for patients (pts) with renal dysfunction or low creatinine (Cr) values in the setting of malnutrition and ascites is unknown. Multiple methods have been utilized to estimate Cr clearance (CrCl) but these perform differently in pts with abnormal Cr values. We sought to determine 1) the relationship between adverse events (AE) and baseline CrCl used for CPRx; 2) the effect on CPRx of using Cockcroft-Gault (CG) +/- the NCI/CTEP recommended limits (CGL), Modification of diet in renal disease (MDRD) or Jelliffe Formula (J) renal function estimates. Methods: Retrospective data were drawn from pts treated on GOG 182, a phase III trial of carboplatin doublet vs triplet or sequential doublet combinations in stage III/IV EOC. For patient safety, the protocol was amended to assign the lower limit of Cr at 0.6mg/dl for CPRx. Area under the receiver operating characteristic curve (AUC) was used to describe associations between CrClJ and various AE. Sensitivity and positive predictive values (PPV) described the AE rate in pts with CrClJ <60ml/min. CPRx for each pt was calculated using J, CG, CGL and MDRD. Results: 3830 evaluable pts had a mean age 58.7yrs, mean BMI 26.8kg/m2 and mean baseline CrClJ 81.9ml/min (range 23.4-239). The AUC statistics (range 0.52-0.64) show that the log(CrClJ) was not a good predictor of grade ≥3 AE (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). A cutoff value of CrClJ <60 ml/min would have deemed 15% of pts treated on GOG182 ineligible. The range of PPV for the above AEs in pts with CrClJ <60 ml/min was 1.8-15%. Using CG, CGL, MDRD instead of J for CPRx would have resulted in >10% decrease in CPRx in 21%, 32% and 12% of pts, respectively. Using CG, CGL, MDRD instead of J for CPRx would have resulted in >10% increase in CPRx in 45%, 9.6% and 5.2% of pts, respectively. Conclusions: Our data do not support excluding patients with CrClJ <60ml/min from clinical trials. The new GOG guidelines replacing J with CGL affect CPRx. The clinical significance of this change with regards to toxicity, particularly in pts with abnormally low Cr values, is yet to be determined.

Tamoxifen in the Treatment of Advanced or Recurrent Endometrial Carcinoma: A Gynecologic Oncology Group Study

2001 ◽  
Vol 19 (2) ◽  
pp. 364-367 ◽  
Author(s):  
Tate Thigpen ◽  
Mark F. Brady ◽  
Howard D. Homesley ◽  
John T. Soper ◽  
Jeffrey Bell
Keyword(s):  
Endometrial Carcinoma ◽  
Systemic Therapy ◽  
Gynecologic Oncology ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Phase Iii Trial ◽  
Free Survival

PURPOSE: In two large Gynecologic Oncology Group studies of patients with advanced or recurrent endometrial carcinoma and no previous systemic therapy, progestins have demonstrated activity against advanced or recurrent endometrial carcinoma with response rates between 15% and 25%. Tamoxifen has been reported as variously active or inactive with or without previous systemic therapy. The purpose of this study was to determine whether tamoxifen exhibits enough activity in patients with advanced or recurrent endometrial carcinoma, who have not received systemic therapy, to warrant a phase III trial. PATIENTS AND METHODS: Sixty-eight eligible patients with advanced or recurrent endometrial carcinoma received oral tamoxifen 20 mg bid until toxicity was unacceptable or disease progressed. RESULTS: Three complete (4%) and four partial (6%) responses were observed for an overall response rate of 10% (90% confidence interval [CI], 5.7% to 17.9%). Patients with tumors that were more anaplastic tended to respond less frequently. The median progression-free survival for all 68 eligible patients was 1.9 months (90% CI, 1.7 to 3.2 months). The median survival was 8.8 months (90% CI, 7.0 to 10.1 months). CONCLUSION: Tamoxifen demonstrated modest activity at best against endometrial carcinoma and does not warrant further investigation as a single agent for this disease. Ongoing trials will assess the sequential use of tamoxifen and progestational agents.

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