Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group Study.

1989 ◽  
Vol 7 (4) ◽  
pp. 457-465 ◽  
Author(s):  
G A Omura ◽  
B N Bundy ◽  
J S Berek ◽  
S Curry ◽  
G Delgado ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Residual Disease ◽  
Gynecologic Oncology ◽  
Dose Schedule ◽  
Stage Iii ◽  
Hematologic Toxicity ◽  
Gynecologic Oncology Group ◽  
Disease Category ◽  
Second Look ◽  
Significant Difference

A randomized clinical trial was conducted in women with stage III ovarian carcinoma (less than or equal to 1 cm residual lesions), using cyclophosphamide plus cisplatin (CP) with or without doxorubicin. There were 349 evaluable patients, of whom 176 received CP while 173 patients received CP plus doxorubicin (CAP). Hematologic toxicity was almost identical. There was no significant difference in progression-free interval (PFI) (median, 22.7 months and 24.6 months), frequency of negative second-look laparotomy (30.2% and 32.8%), or survival (median, 31.2 months and 38.9 months) between CP and CAP, respectively. Thus, doxorubicin in the dose schedule employed does not improve combination chemotherapy of optimal stage III ovarian carcinoma. Several other findings, independent of treatment arm, were of interest. There was a significant difference in PFI and survival by residual disease category (yes v no) and by grade of differentiation (1 v 2 + 3). In multivariate analysis, age, residual disease at entry, cell type (clear cell carcinoma), and time from surgery to initiation of chemotherapy were significant predictors of survival. There was no difference in outcome comparing those who refused second-look with those who had a second-look.

Intraperitoneal Radioactive Phosphorus (32P) Versus Observation After Negative Second-Look Laparotomy for Stage III Ovarian Carcinoma: A Randomized Trial of the Gynecologic Oncology Group

2003 ◽  
Vol 21 (15) ◽  
pp. 2849-2855 ◽  
Author(s):  
Mahesh A. Varia ◽  
Frederick B. Stehman ◽  
Brian N. Bundy ◽  
Jo Ann Benda ◽  
Daniel L. Clarke-Pearson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Relative Risk ◽  
Ovarian Carcinoma ◽  
Tumor Recurrence ◽  
Stage Iii ◽  
Gynecologic Oncology Group ◽  
Consolidation Therapy ◽  
Risk Of Death ◽  
Second Look ◽  
Significant Difference

Purpose: The objectives of this prospective randomized study of consolidation therapy were to evaluate recurrence-free survival (RFS), overall survival (OS), and the morbidity of intraperitoneal (IP) chromic phosphate suspension (32P) therapy in patients with stage III epithelial ovarian carcinoma who have no detectable evidence of disease at the second-look laparotomy (SLL) procedure after primary chemotherapy. Patients and Methods: In a multi-institution clinical cooperative trial, 202 eligible patients with a negative SLL were randomly selected to receive either 15 mCi IP 32P (n = 104) or no further therapy (NFT; n = 98). Results: With a median follow-up of 63 months in living patients, 68 patients in the IP 32P group (65%) and 63 patients in the NFT group (64%) have developed tumor recurrence. The relative risk of recurrence is 0.90 (IP 32P to NFT) (90% confidence interval [CI], 0.68 to 1.19). The 5-year RFS rate is 42% and 36% for the IP 32P and NFT groups, respectively; the difference is not statistically significant (log-rank test, P = .27). There was no statistically significant difference in OS (P = .19). The relative risk of death is 0.85 (IP 32P to NFT) (90% CI, 0.62 to 1.16). Sixteen patients (8%) experienced grade 3 or 4 adverse effects, with eight in each respective group. Conclusion: Intraperitoneal chromic phosphate did not decrease the risk of relapse or improve survival for patients with stage III epithelial ovarian cancer after a negative SLL. Despite complete pathologic remission at SLL after initial surgery and platinum-based chemotherapy, 61% of stage III ovarian cancer patients had tumor recurrence within 5 years of negative SLL. This indicates a need for more effective initial therapy and further studies of consolidation therapy.

Long-term follow-up and prognostic factor analysis in advanced ovarian carcinoma: the Gynecologic Oncology Group experience.

1991 ◽  
Vol 9 (7) ◽  
pp. 1138-1150 ◽  
Author(s):  
G A Omura ◽  
M F Brady ◽  
H D Homesley ◽  
E Yordan ◽  
F J Major ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Clear Cell ◽  
Gynecologic Oncology ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Advanced Ovarian Carcinoma ◽  
Second Look ◽  
Long Term Follow Up

Long-term follow-up was obtained on 726 women with advanced ovarian carcinoma (suboptimal stage III and stage IV) who had received primary chemotherapy on two Gynecologic Oncology Group (GOG) protocols between 1976 and 1982. The first study compared melphalan alone versus melphalan plus hexamethylmelamine versus cyclophosphamide plus doxorubicin (CA). The second study evaluated the same CA regimen with or without cisplatin. Eligibility for the two studies was the same. At last contact, 76 patients were alive. In a multivariate analysis, cell type other than clear cell or mucinous, cisplatin-based treatment, good performance status, younger age, lower stage, clinically nonmeasurable disease, smaller residual tumor volume, and absence of ascites were favorable characteristics for overall survival (P less than .05). Second-look laparotomy was negative significantly more often among those with endometrioid tumors; there were no negative second-look laparotomies among those with mucinous or clear cell tumors. There were 30 patients with suboptimal stage III disease who had a negative second-look laparotomy; 18 (60%) have experienced recurrence, and 13 (43%) have died. Although cisplatin treatment was beneficial, new treatments are clearly needed.

Second-look laparotomy in the patient with minimal residual stage III ovarian cancer (a Gynecologic Oncology Group study)

1989 ◽  
Vol 35 (3) ◽  
pp. 378-382 ◽  
Author(s):  
William T. Creasman ◽  
Stanley Gall ◽  
Brian N. Bundy ◽  
Jackson Beecham ◽  
Rodrigue Mortel ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gynecologic Oncology ◽  
Stage Iii ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Oncology Group Study ◽  
Second Look ◽  
Minimal Residual

Phase I and pharmacologic study of the combination paclitaxel and carboplatin as first-line chemotherapy in stage III and IV ovarian cancer.

1997 ◽  
Vol 15 (5) ◽  
pp. 1953-1964 ◽  
Author(s):  
M T Huizing ◽  
L J van Warmerdam ◽  
H Rosing ◽  
M C Schaefers ◽  
A Lai ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Residual Disease ◽  
Single Agent ◽  
Stage Iv ◽  
Maximum Tolerated Dose ◽  
Stage Iii ◽  
Hematologic Toxicity ◽  
Time Curve ◽  
Second Look

PURPOSE To determine the maximum-tolerated dose for the combination paclitaxel and carboplatin administered every 4 weeks and to gain more insight into the pharmacokinetics and pharmacodynamics of this combination in previously untreated ovarian cancer patients. PATIENTS AND METHODS Thirty-five chemotherapy-naive patients with suboptimally debulked stage III (tumor masses > 3 cm) and stage IV ovarian cancer were entered onto this phase I trial in which paclitaxel was administered as a 3-hour intravenous (IV) infusion at dosages of 125 to 225 mg/m2 immediately followed by carboplatin over 30 minutes at dosages of 300 to 600 mg/m2. A total of six courses was planned, followed by a second-look laparoscopy/laparotomy. Patients with a response and/or minimal residual disease at second-look laparoscopy received three additional courses. Twenty-six patients participated in the pharmacokinetic part of the study. RESULTS The most important hematologic toxicity encountered was neutropenia. Neutropenia was more pronounced for the higher dose levels (DLs) and was cumulative. Thrombocytopenia was mild in the first eight DLs, but increased during the treatment courses. Nonhematologic toxicities consisted mainly of vomiting, neuropathy, fatigue, rash, pruritus, myalgia, and arthralgia. Dose-limiting toxicities (DLTs) in this trial were neutropenic fever, thrombocytopenia that required platelet transfusions, and cumulative neuropathy. Of 33 patients assessable for response, 26 major responders (78%, 20 complete response [CR] and six partial response [PR]) were documented. The maximal concentration (Cmax) of paclitaxel and the area under the concentration-time curve (AUC) were not different from the historical data for paclitaxel as a single agent. Retrospective analysis using a modified Calvert formula showed that the measured carboplatin AUCs in plasma ultrafiltrate (pUF) were 30% +/- 3.4% less than the calculated carboplatin AUC. Neutropenia was more pronounced than could be expected on the basis of the historical times above a threshold concentration greater than 0.1 mumol/L (T > or = 0.1 mumol/L) or 0.05 mumol/L (T > or = 0.05 mumol/L), and thrombocytopenia was less than could be expected from historical sigmoidal Emax models. CONCLUSION The combination of paclitaxel 200 mg/ m2 and carboplatin 550 mg/m2 every 4 weeks is a well-tolerated treatment modality. The paclitaxel-carboplatin combination is highly active in stage III (bulky) and stage IV ovarian cancer. No indications for a pharmacokinetic drug-drug interaction between carboplatin and paclitaxel were found.

Prognostic Factors for Stage III Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study

2007 ◽  
Vol 25 (24) ◽  
pp. 3621-3627 ◽  
Author(s):  
William E. Winter ◽  
G. Larry Maxwell ◽  
Chunqiao Tian ◽  
Jay W. Carlson ◽  
Robert F. Ozols ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Factors ◽  
Epithelial Ovarian Cancer ◽  
Poor Prognosis ◽  
Residual Disease ◽  
Gynecologic Oncology ◽  
Small Sample ◽  
Stage Iii ◽  
Gynecologic Oncology Group ◽  
Increased Risk

Purpose Conflicting results on prognostic factors for advanced epithelial ovarian cancer (EOC) have been reported because of small sample size and heterogeneity of study population. The purpose of this study was to identify factors predictive of poor prognosis in a similarly treated population of women with advanced EOC. Patients and Methods A retrospective review of demographic, pathologic, treatment, and outcome data from 1,895 patients with International Federation of Gynecology and Obstetrics stage III EOC who had undergone primary surgery followed by six cycles of intravenous platinum/paclitaxel was conducted. A proportional hazards model was used to assess the association of prognostic factors with progression-free survival (PFS) and overall survival (OS). Results Increasing age was associated with increased risks for disease progression (HR = 1.06; 95% CI, 1.02 to 1.11 for an increase every 10 years) and death (HR = 1.12; 95% CI, 1.06 to 1.18). Mucinous or clear-cell histology was associated with a worse PFS and OS compared with serous carcinomas. Patients with performance status (PS) 1 or 2 were at an increased risk for recurrence compared with PS 0 (HR = 1.12; 95% CI, 1.01 to 1.24). Compared with patients with microscopic residual disease, patients with 0.1 to 1.0 cm and > 1.0 cm residual disease had an increased risk of recurrence (HR = 1.96; 95% CI, 1.70 to 2.26; and HR = 2.36; 95% CI, 2.04 to 2.73, respectively) and death (HR = 2.11; 95% CI, 1.78 to 2.49; P < .001; and HR = 2.47; 95% CI, 2.09 to 2.92, respectively). Conclusion Age, PS, tumor histology, and residual tumor volume were independent predictors of prognosis in patients with stage III EOC. These data can be used to identify patients with poor prognosis and to design future tailored randomized clinical trials.

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]

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