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.

Addition of Epirubicin As a Third Drug to Carboplatin-Paclitaxel in First-Line Treatment of Advanced Ovarian Cancer: A Prospectively Randomized Gynecologic Cancer Intergroup Trial by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group and the Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens

2006 ◽  
Vol 24 (7) ◽  
pp. 1127-1135 ◽  
Author(s):  
Andreas du Bois ◽  
Beatrice Weber ◽  
Justine Rochon ◽  
Werner Meier ◽  
Alain Goupil ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Survival Time ◽  
Gynecologic Cancer ◽  
Survival Rates ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
First Line ◽  
Term Survival ◽  
Advanced Epithelial Ovarian Cancer

Purpose Despite the progress that has been achieved, long-term survival rates in patients with advanced ovarian cancer are still disappointing. One attempt to improve results could be the addition of non–cross-resistant drugs to platinum-paclitaxel combination regimens. Anthracyclines were among the candidates for incorporation as a third drug into first-line regimens. Patients and Methods We performed a prospectively randomized phase III study comparing carboplatin-paclitaxel (TC; area under the curve 5/175 mg/m2, respectively) with epirubicin 60 mg/m2 added to the same combination (TEC) in previously untreated patients with advanced epithelial ovarian cancer. All drugs were administered intravenously on day 1 of a 3-week schedule for a planned minimum of six courses. Results Between November 1997 and February 2000, 1,282 patients were randomly assigned to receive either TC (635 patients) or TEC (647 patients), respectively. Grade 3/4 hematologic and some nonhematologic toxicities (nausea/emesis, mucositis, and infections) occurred significantly more frequently in the TEC arm. Accordingly, quality-of-life analysis showed inferiority of TEC versus TC. Median progression-free survival time was 18.4 months for the TEC arm and 17.9 months for the TC arm (hazard ratio [HR], 0.95; 95% CI, 0.83 to 1.07; P = .3342). Median overall survival time was 45.8 months for the TEC arm and 41.0 months for the TC arm (HR, 0.93; 95% CI, 0.81 to 1.08; P = .3652). Similar nonsignificant differences were observed when strata were analyzed separately. Conclusion Addition of epirubicin to TC did not improve survival or time to treatment failure in patients with advanced epithelial ovarian cancer; therefore, it cannot be recommended for clinical use in this population.

Carboplatin plus paclitaxel (CP) versus carboplatin plus stealth liposomal doxorubicin (CLD) in patients with advanced ovarian cancer (AOC): Activity and safety results of the MITO-2 randomized multicenter trial

2009 ◽  
Vol 27 (18_suppl) ◽  
pp. LBA5508-LBA5508 ◽  
Author(s):  
S. Pignata ◽  
G. Scambia ◽  
A. Savarese ◽  
R. Sorio ◽  
E. Breda ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Objective Response ◽  
Haematological Toxicity ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Activity Analysis ◽  
Phase Iii ◽  
Ca 125 ◽  
First Line

LBA5508 Background: CP is standard first-line chemotherapy for AOC. MITO-2 (Multicentre Italian Trials in Ovarian Cancer) is an academic randomized phase III study testing whether CLD is more effective than CP. Methods: AOC patients (pts), stage IC-IV, aged≤75, ECOG PS≤2, were randomized to CP (C AUC5 + P 175 mg/m2,d1q21) or to CLD (C AUC5 + LD 30 mg/m2,d1q21), both for 6 cycles. Primary endpoint is progression-free survival (PFS). Secondary endpoints are overall survival, objective response rate (ORR), toxicity and quality of life. To have 80% power in detecting a 0.80 HR in PFS, with 2-sided α error 0.05, 632 events are needed and 820 pts were planned. Activity was evaluated according to RECIST, toxicity according to NCI-CTC. Activity analysis was not blinded and no confirmation of response was required. Results: From January 2003 to November 2007, 820 pts were randomized, 410 to each arm. Median age was 57 yrs (range 21–77). Stage III (60%) and IV (22%) were prevalent. As of March 30, 2009, with a median follow-up of 35 months, 530 events for PFS and 269 deaths have been recorded. Six cycles were received by 86% and 80% of pts, with CP and CLD respectively. With complete data for 97% of pts, 290 pts were eligible for activity analysis (≥1 target lesion). ORR was 59% with CP and 57% with CLD (p=0.70). In 182 pts with non-target lesions only, complete response was 33% with CP and 29% with CLD (p=0.64). In 168 pts with elevated CA-125 only, CA-125 normalization was obtained in 83% with CP and 86% with CLD (p=0.56). Toxicity data are complete for 97% of pts. Statistically significant differences in haematological toxicity (CP vs CLD) were: anemia all grades 59% vs 68%, grade (G) 3–4 4% vs 10%; thrombocytopenia all grades 19% vs 48%, G3–4 2% vs 16%. Statistically significant differences in non haematological toxicity were: hair loss 63% vs 14%; skin toxicity all grades 6% vs 20%, G3–4 0 vs 2%; diarrhea all grades 13% vs 6%; stomatitis all grades 9% vs 20%; neurotoxicity all grades 47% vs 15%, G3–4 3% vs 0.3%. Conclusions: CLD as first-line treatment of AOC produced a similar activity, with a different toxicity profile, compared to CP. Required events are awaited for final PFS analysis. Partially supported by Schering-Plough. No significant financial relationships to disclose.

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.

Randomized Phase III Study of Temozolomide Versus Dacarbazine in the Treatment of Patients With Advanced Metastatic Malignant Melanoma

2000 ◽  
Vol 18 (1) ◽  
pp. 158-158 ◽  
Author(s):  
M.R. Middleton ◽  
J.J. Grob ◽  
N. Aaronson ◽  
G. Fierlbeck ◽  
W. Tilgen ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Objective Response ◽  
Area Under The Curve ◽  
Systemic Exposure ◽  
Parent Drug ◽  
Progression Free Survival ◽  
Treated Group ◽  
Phase Iii ◽  
Health Related ◽  
Moderate Nausea

PURPOSE: : To compare, in 305 patients with advanced metastatic melanoma, temozolomide and dacarbazine (DTIC) in terms of overall survival, progression-free survival (PFS), objective response, and safety, and to assess health-related quality of life (QOL) and pharmacokinetics of both drugs and their metabolite, 5-(3-methyltriazen-1-yl)imidazole-4-carboximide (MTIC). PATIENTS AND METHODS: Patients were randomized to receive either oral temozolomide at a starting dosage of 200 mg/m2/d for 5 days every 28 days or intravenous (IV) DTIC at a starting dosage of 250 mg/m2/d for 5 days every 21 days. RESULTS: In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P = .012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75). No major difference in drug safety was observed. Temozolomide was well tolerated and produced a noncumulative, transient myelosuppression late in the 28-day cycle. The most common nonhematologic toxicities were mild to moderate nausea and vomiting, which were easily managed. Temozolomide therapy improved health-related QOL; more patients showed improvement or maintenance of physical functioning at week 12. Systemic exposure (area under the curve) to the parent drug and the active metabolite, MTIC, was higher after treatment with oral temozolomide than after IV administration of DTIC. CONCLUSION: Temozolomide demonstrates efficacy equal to that of DTIC and is an oral alternative for patients with advanced metastatic melanoma.

Clinical experience of using docetaxel-cisplatin in the treatment of advanced ovarian cancer: A Bangladesh perspective

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15070-15070
Author(s):  
M. Mokhlesuddin ◽  
P. S. Akhter ◽  
D. U. Ahmed ◽  
M. A. Khan ◽  
M. A. Rahman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Active Agent ◽  
Advanced Ovarian Cancer ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Advanced Epithelial Ovarian Cancer ◽  
Bangladeshi Population

15070 Background: Docetaxel is an active agent in the treatment of recurrent advanced ovarian cancer. We conducted a multi-center phase II study to evaluate the response rate, toxicity and survival of docetaxel-cisplatin regimen as first-line treatment of advanced ovarian cancer in Bangladeshi population. Methods: Forty chemotherapy-naïve patients of advanced epithelial ovarian cancer were recruited between October 1999 to March 2002. Eligibility criteria included stage Ic-IV patients, age 18–75 years, an ECOG performance status of 0–3 with adequate hepatic, renal and bone marrow function. Docetaxel 60 mg/m2 as 1 hour IV infusion and cisplatin 75 mg/m2 were given on day 1 every 3 weeks for a maximum of 6 cycles (average 5 cycles). Tumor responses and toxicities were evaluated by relevant investigations and survival was documented. Results: A total of 40 patients were enrolled. Median age was 44 years (age range 18–75 years). All the patients were evaluable for response. Overall response was observed in 32 patients (80%) with complete response rate 38% (12 patients), partial response rate 62% (20 patients). Stable disease was seen in 5 patients (12.5%) and progressive disease was in 3 patients (7.5%).Two years survival was documented in 62% patients. Toxicities were limited with grade 3 neutropenia in 10 patients (25%) and some non-hematological toxicities (including nausea, vomiting and fluid retention) in twenty-six patients (65%). No severe febrile neutropenia and no events of death were observed. Conclusions: The combination of docetaxel and cisplatin appears to be effective with manageable toxicities in patients with advanced epithelial ovarian cancer in Bangladeshi population. No significant financial relationships to disclose.

Final results of After-6 protocol 1: A phase III trial of observation versus 6 courses of paclitaxel (Pac) in advanced ovarian cancer patients in complete response (CR) after platinum-paclitaxel chemotherapy (CT)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5505-5505 ◽  
Author(s):  
P. F. Conte ◽  
G. Favalli ◽  
A. Gadducci ◽  
D. Katsaros ◽  
P. L. Benedetti Panici ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Survival Rates ◽  
Advanced Ovarian Cancer ◽  
Stage Iv ◽  
Experimental Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
First Line ◽  
Absolute Increase

5505 Background: The majority of advanced ovarian cancer patients (pts) in CR after debulking surgery and Platinum/Paclitaxel will eventually relapse. Role of maintenance CT is still questionable even if a SWOG/GOG trial has shown an improved progression free survival (PFS) with 12 vs 3 cycles of maintenance Pac. In March 1999, the After 6 Italian Cooperative Group initiated a phase III study to determine if maintenance Pac could prolong PFS in pts with a clinical (cCR) or pathological CR (pCR) after first line CT Methods: Pts with advanced ovarian cancer in cCR or pCR after 6 cycles of Platinum/Paclitaxel, were randomised to observation or 6 cycles of Pac 175 mg/sqm iv q 3 wks. Primary end point: PFS; secondary end points: overall survival (OS) and toxicities. Planned sample size: 250 pts to detect a 15% absolute increase in 2-yr PFS. Results: From 03/99 to 07/06, 200 pts were randomised. Due to the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Main patient characteristics: median age 58 yrs, median PS 0 (neurotoxicity ≥ G 2 was an exclusion criteria), stage IIb/IIc 15%, stage III 79%, stage IV 6%; 105 pts (52.5%) were in pCR. 14% of pts randomised to observation received Pac; 22% of pts randomised to Pac stopped treatment after 2–5 cycles (progression or death: 3 pts; toxicity: 9 pts; refusal: 7 pts; others: 3 pts). A G ≥ 2 neurotoxicity was reported in 25% of pts treated with Pac; other toxicities were mild. After a median follow up of 44 months, 94 pts (47%) have relapsed and 42 pts (21%) died. Median PFS were 34 and 34.5 months in observation and Pac arm respectively; 3-yr OS was 88% in observation and 78% in Pac arm. Irrespectively of treatment arm, median PFS was 34.4 months for pts with pCR and 24.5 months for those with cCR; 3-yr survival rates were 87% and 79% respectively (p=0.04). Conclusions: Six courses of maintenance Pac do not prolong PFS or OS in pts in CR after first line platinum/paclitaxel. Irrespectively of assigned treatment, the outcome of these pts is more favourable than previously reported and significantly better in the pCRs. Maintenance CT remains an experimental treatment that should be tested in pts at high risk of relapse. [Table: see text]

A clinical study of tremelimumab alone or in combination with olaparib in patients with advanced epithelial ovarian cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6045-6045
Author(s):  
Stephanie Gaillard ◽  
Maureen Berg ◽  
Jeanne Harrison ◽  
Peng Huang ◽  
James M. Leatherman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Epithelial Ovarian Cancer ◽  
Single Agent ◽  
Objective Response ◽  
Optimal Dose ◽  
Clinical Activity ◽  
Immune Mediated ◽  
Advanced Epithelial Ovarian Cancer ◽  
Dose Levels

6045 Background: Single agent immunotherapy (IO) has shown only modest clinical activity for the treatment of ovarian cancer. The combination of anti-programmed death-1 and PARP inhibitors showed promising activity in early trials. Here, we report the results of an open-label, parallel arm, dose escalation study of tremelimumab (T) alone or in combination with olaparib (O) in patients (pts) with advanced epithelial ovarian cancer (EOC). Methods: Pts with recurrent/persistent EOC who had progression < 12 months from last platinum exposure were enrolled. Prior therapy with IO (except anti-CTLA-4) or PARP inhibitor was allowed. Pts were randomized to either T 10mg/kg every 4 weeks (wks) x 7 then every 12 wks (Arm A) or T with O twice daily at three planned dose levels (Arm B). The primary objectives were safety, pharmacodynamic (PD) change in CD4+ICOShi peripheral T cells by flow cytometry, and identification of the optimal dose combination of T with O. Secondary objectives included 6-month progression-free survival (PFS6) and objective response rate (ORR). Results: A total of 24 pts were treated, 12 on Arm A, and 12 on two Arm B dose levels. Pts had a median age of 60 years (range 44-81). Histologic subtypes included high-grade serous EOC (20 pts, 83%), clear cell (3 pts, 13%), and moderately-differentiated adenocarcinoma (1 pt, 4%). BRCA1 mutation (mt) was present in 2 cases, BRCA2 mt in 1. Median number of prior regimens was 3.5 (range 1-9). Most adverse events (AEs) were attributable to T, the most common grade 3 toxicities were rash (13%), immune-mediated hepatitis (8%), and colitis (8%). No grade ≥4 toxicities were identified. Immune-mediated AEs also included acute kidney injury, hypophysitis, and hypothyroidism. No dose limiting toxicities were identified on Arm B. Two pts in Arm B had >PFS6. Of 20 pts evaluable for response, there was 1 partial response (Arm B), and 9 pts had stable disease (6 on Arm A, 3 on Arm B). Mean percentage of CD4+ICOShi T cells was significantly increased on Days 15 and 22 compared to Day 1 at both T dose levels (Table).T at 3 mg/kg with O at 150mg is the optimal dose of those tested. Conclusions: T and T with O was tolerable, with modest clinical activity in this pt population. AEs were as expected, and peripheral CD4+ICOShi T cells increased on therapy. Clinical trial information: 02485990. [Table: see text]

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