Quality-of-life outcomes from a randomized phase III trial of dose-dense weekly paclitaxel and carboplatin compared with conventional paclitaxel and carboplatin as a first-line treatment for stage II–IV ovarian cancer: Japanese Gynecologic Oncology Group Trial (JGOG3016)

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.

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Randomized Phase III Trial of Gemcitabine Plus Docetaxel Plus Bevacizumab or Placebo As First-Line Treatment for Metastatic Uterine Leiomyosarcoma: An NRG Oncology/Gynecologic Oncology Group Study

Journal of Clinical Oncology ◽

10.1200/jco.2014.58.3781 ◽

2015 ◽

Vol 33 (10) ◽

pp. 1180-1185 ◽

Cited By ~ 68

Author(s):

Martee L. Hensley ◽

Austin Miller ◽

David M. O'Malley ◽

Robert S. Mannel ◽

Kian Behbakht ◽

...

Keyword(s):

Controlled Trial ◽

Gynecologic Oncology ◽

Objective Response ◽

Phase Iii ◽

Fixed Dose ◽

Uterine Leiomyosarcoma ◽

Gynecologic Oncology Group ◽

Line Treatment ◽

First Line ◽

First Line Treatment

Purpose Fixed-dose rate gemcitabine plus docetaxel achieves objective response in 35% of patients with uterine leiomyosarcoma (uLMS). This study aimed to determine whether the addition of bevacizumab to gemcitabine-docetaxel increases progression-free survival (PFS) in uLMS. Patients and Methods In this phase III, double-blind, placebo-controlled trial, patients with chemotherapy-naive, metastatic, unresectable uLMS were randomly assigned to gemcitabine-docetaxel plus bevacizumab or gemcitabine-docetaxel plus placebo. PFS, overall survival (OS), and objective response rates (ORRs) were compared to determine superiority. Target accrual was 130 patients to detect an increase in median PFS from 4 months (gemcitabine-docetaxel plus placebo) to 6.7 months (gemcitabine-docetaxel plus bevacizumab). Treatment effects on PFS and OS were described by hazard ratios (HRs), median times to event, and 95% CIs. Results In all, 107 patients were accrued: gemcitabine-docetaxel plus placebo (n = 54) and gemcitabine-docetaxel plus bevacizumab (n = 53). Accrual was stopped early for futility. No statistically significant differences in grade 3 to 4 toxicities were observed. Median PFS was 6.2 months for gemcitabine-docetaxel plus placebo versus 4.2 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.12; P = .58). Median OS was 26.9 months for gemcitabine-docetaxel plus placebo and 23.3 months for gemcitabine-docetaxel plus bevacizumab (HR, 1.07; P = .81). Objective responses were observed in 17 (31.5%) of 54 patients randomly assigned to gemcitabine-docetaxel plus placebo and 19 (35.8%) of 53 patients randomly assigned to gemcitabine-docetaxel plus bevacizumab. Mean duration of response was 8.6 months for gemcitabine-docetaxel plus placebo versus 8.8 months for gemcitabine-docetaxel plus bevacizumab. Conclusion The addition of bevacizumab to gemcitabine-docetaxel for first-line treatment of metastatic uLMS failed to improve PFS, OS, or ORR. Gemcitabine-docetaxel remains a standard first-line treatment for uLMS.

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Phase III Trial of Four Cisplatin-Containing Doublet Combinations in Stage IVB, Recurrent, or Persistent Cervical Carcinoma: A Gynecologic Oncology Group Study

Journal of Clinical Oncology ◽

10.1200/jco.2009.21.8909 ◽

2009 ◽

Vol 27 (28) ◽

pp. 4649-4655 ◽

Cited By ~ 372

Author(s):

Bradley J. Monk ◽

Michael W. Sill ◽

D. Scott McMeekin ◽

David E. Cohn ◽

Lois M. Ramondetta ◽

...

Keyword(s):

Cervical Carcinoma ◽

Gynecologic Oncology ◽

Progression Free Survival ◽

Phase Iii ◽

Gynecologic Oncology Group ◽

Phase Iii Trial ◽

Hazard Ratios ◽

Early Closure ◽

Stage Ivb

Purpose Assess toxicity and efficacy of cisplatin (Cis) doublet combinations in advanced and recurrent cervical carcinoma. Patients and Methods Patients were randomly assigned to paclitaxel 135 mg/m2 over 24 hours plus Cis 50 mg/m2 day 2 every 3 weeks (PC, reference arm); vinorelbine 30 mg/m2 days 1 and 8 plus Cis 50 mg/m2 day 1 every 3 weeks (VC); gemcitabine 1,000 mg/m2 day 1 and 8 plus Cis 50 mg/m2 day 1 every 3 weeks (GC); or topotecan 0.75 mg/m2 days 1, 2, and 3 plus Cis 50 mg/m2 day 1 every 3 weeks (TC). Survival was the primary end point with a 33% improvement relative to PC considered important (85% power, alpha = 5%). Quality-of-life data were prospectively collected. Results A total of 513 patients were enrolled when a planned interim analysis recommended early closure for futility. The experimental-to-PC hazard ratios of death were 1.15 (95% CI, 0.79 to 1.67) for VC, 1.32 (95% CI, 0.91 to 1.92) for GC, and 1.26 (95% CI, 0.86 to 1.82) for TC. The hazard ratios for progression-free survival (PFS) were 1.36 (95% CI, 0.97 to 1.90) for VC, 1.39 (95% CI, 0.99 to 1.96) for GC, and 1.27 (95% CI, 0.90 to 1.78) for TC. Response rates (RRs) for PC, VC, GC, and TC were 29.1%, 25.9%, 22.3%, and 23.4%, respectively. The arms were comparable with respect to toxicity except for leucopenia, neutropenia, infection, and alopecia. Conclusion VC, GC, and TC are not superior to PC in terms of overall survival (OS). However, the trend in RR, PFS, and OS favors PC. Differences in chemotherapy scheduling, pre-existing morbidity, and toxicity are important in individualizing therapy.

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