David E Cohn1, Michael W Sill2, Joan L Walker3, David O'Malley4, Christa I Nagel5, Teresa L Rutledge6, William Bradley7, Debra L Richardson8, Katherine M Moxley9, Carol Aghajanian10. 1. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, United States. Electronic address: David.Cohn@osumc.edu. 2. NRG Oncology/Gynecologic Oncology Group, Statistics & Data Management, Roswell Park Cancer Institute, Buffalo, NY, United States. Electronic address: msill@gogstats.org. 3. Department of OB/GYN, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States. Electronic address: joan-walker@ouhsc.edu. 4. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, United States. Electronic address: omalley.46@osu.edu. 5. Dept of Gynecologic Oncology, Case Western Reserve University, Cleveland, OH 44106, United States. Electronic address: Christa.Nagel@uhhospitals.org. 6. Division of Gyn/Oncology, University of New Mexico, Albuquerque, NM 87131, United States. Electronic address: trutledge@salud.unm.edu. 7. Dept. of OB/GYN, Medical College of Wisconsin, Milwaukee, WI 53226, United States. Electronic address: wbradley@mcw.edu. 8. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 95390-9032, United States. Electronic address: Debra.richardson@utsouthwestern.edu. 9. Department of OB/GYN, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States. Electronic address: katherine-moxley@ouhsc.edu. 10. Department of Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 120021, United States. Electronic address: aghajanc@mskcc.org.
Abstract
OBJECTIVE: To assess whether the addition of oncolytic reovirus (Reolysin®) to weekly paclitaxel prolonged progression-free survival (PFS) in the treatment of women with recurrent or persistent ovarian, tubal or primary peritoneal cancer. PATIENTS AND METHODS: Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to paclitaxel (80mg/m2 intravenously days 1, 8, and 15 every 4weeks) or the combination of paclitaxel (80mg/m2 intravenously days 1, 8, and 15) plus reovirus 3×1010TCID50/day intravenously on days 1-5, both every 4weeks until disease progression or toxicity. The primary end point was PFS. The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%. RESULTS: The study accrued 108 patients, 100 of whom were evaluable for toxicity. Median PFS was 4.3months for paclitaxel and 4.4months for paclitaxel plus reovirus (hazard ratio, 1.11; 90% two-sided CI, 0.78 to 1.59; one-sided P=0.687). The proportion responding (overall response rate) to paclitaxel was 20% among 45 patients with measurable disease receivingpaclitaxel alone, and 17.4% among the 46 patients treated with the combination. The asymptotic relative probability of responding was 0.87 (90% CI, 0.42 to 1.79). Severe adverse events were more common in the combination regimen than in paclitaxel arm for severe neutropenia (grade≥4, 12% versus 0%), and severe respiratory adverse events (grade≥3, 25% versus 2%). No deaths were considered treatment related. CONCLUSION: The addition of reovirus to weekly paclitaxel in the treatment of women with recurrent or persistent ovarian, tubal or peritoneal cancer did not sufficiently reduce the hazard of progression or death to warrant further investigation.
RCT Entities:
OBJECTIVE: To assess whether the addition of oncolytic reovirus (Reolysin®) to weekly paclitaxel prolonged progression-free survival (PFS) in the treatment of women with recurrent or persistent ovarian, tubal or primary peritoneal cancer. PATIENTS AND METHODS: Patients with recurrent or persistent epithelial ovarian, tubal, or peritoneal carcinoma, measurable or detectable disease, and three or fewer prior regimens were randomly assigned to paclitaxel (80mg/m2 intravenously days 1, 8, and 15 every 4weeks) or the combination of paclitaxel (80mg/m2 intravenously days 1, 8, and 15) plus reovirus 3×1010TCID50/day intravenously on days 1-5, both every 4weeks until disease progression or toxicity. The primary end point was PFS. The study was designed with 80% power for a one-sided alternative at a 10% level of significance to detect a reduction in the hazard by 37.5%. RESULTS: The study accrued 108 patients, 100 of whom were evaluable for toxicity. Median PFS was 4.3months for paclitaxel and 4.4months for paclitaxel plus reovirus (hazard ratio, 1.11; 90% two-sided CI, 0.78 to 1.59; one-sided P=0.687). The proportion responding (overall response rate) to paclitaxel was 20% among 45 patients with measurable disease receiving paclitaxel alone, and 17.4% among the 46 patients treated with the combination. The asymptotic relative probability of responding was 0.87 (90% CI, 0.42 to 1.79). Severe adverse events were more common in the combination regimen than in paclitaxel arm for severe neutropenia (grade≥4, 12% versus 0%), and severe respiratory adverse events (grade≥3, 25% versus 2%). No deaths were considered treatment related. CONCLUSION: The addition of reovirus to weekly paclitaxel in the treatment of women with recurrent or persistent ovarian, tubal or peritoneal cancer did not sufficiently reduce the hazard of progression or death to warrant further investigation.
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