TY - JOUR
T1 - A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus
T2 - A Gynecologic Oncology Group study
AU - Sutton, Gregory
AU - Brunetto, Virginia L.
AU - Kilgore, Larry
AU - Soper, John T.
AU - McGehee, Ramon
AU - Olt, George
AU - Lentz, Samuel S.
AU - Sorosky, Joel
AU - Hsiu, Jeng Gwang
N1 - Funding Information:
This study was supported by National Cancer Institute grants of the Gynecologic Oncology Group Administrative Office (CA 27469) and the Gynecologic Oncology Group Statistical Office (CA 37517). The following Gynecologic Oncology Group institutions participated in this study: University of Alabama at Birmingham, Oregon Health Sciences Center, Duke University Medical Center, Abington Memorial Hospital, University of Rochester Medical Center, Walter Reed Army Medical Center, Wayne State University School of Medicine, University of Minnesota Medical School, Emory University Clinic, University of Southern California Medical Center at Los Angeles, University of Mississippi Medical Center, Colorado Foundation for Medical Care, University of California Medical Center at Los Angeles, Hospital of the University of Pennsylvania, University of Miami School of Medicine, The Milton S. Hershey School of Medicine of the Pennsylvania State University, Georgetown University Hospital, University of North Carolina School of Medicine, University of Iowa Hospitals and Clinics, University of Texas Health Science Center at Dallas, Indiana University Medical Center, Wake Forest School of Medicine, The Albany Medical College of Union University, University of California Medical Center at Irvine, Tufts New England Medical Center, Rush–Presbyterian–St. Lukes Medical Center, State University of New York Downstate Medical Center, University of Kentucky, Eastern Virginia Medical School, Cleveland Clinic Foundation, The Johns Hopkins Oncology Center, State University of New York at Stony Brook, Pennsylvania Hospital, Washington University School of Medicine, Memorial Sloan-Kettering Cancer Center, Cooper Hospital University Medical Center, Columbus Cancer Council, University of Massachusetts Medical Center, Fox Chase Cancer Center, Medical University of South Carolina, Women’s Cancer Center, University of Oklahoma Health Science Center, University of Virginia Health Science Center, University of Chicago, University of Arizona Health Science Center, Thomas Jefferson University Hospital, Mayo Clinic, and Case Western Reserve University.
PY - 2000
Y1 - 2000
N2 - Objective. The aims of this study were to substantiate the previously reported activity of ifosfamide in patients with advanced, persistent, or recurrent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determine whether the addition of cisplatin results in an improved response or survival. Secondarily, we sought to determine the toxicity of ifosfamide-cisplatin in this patient population. Methods. Patients were randomized to receive ifosfamide (1.5 g/m2/day) times 5 days every 3 weeks for eight courses with mesna uroprotection, with or without cisplatin (20 mg/m2/day) times 5 days. No patient had received previous chemotherapy. Results. Of 224 patients entered on this study, 30 were ineligible for a variety of reasons, leaving 194 evaluable patients. Early in the study, the dose of the combination regimen was reduced by 20% (1 day) because of toxicity. The investigational arms were balanced for age, grade, and Gynecologic Oncology Group performance status. Percentages, of adverse effects reported in 191 patients receiving chemotherapy included (ifosfamide/cisplatin-ifosfamide) grade 3 or 4 granulocytopenia (36/60), grade 3 or 4 anemia (8/17), grade 3 or 4 central nervous system toxicity (19/14), and grade 3 or 4 peripheral neuropathy (1/12). Treatment may have contributed to the deaths of 6 patients treated with full doses of ifosfamide and cisplatin for 5 days. The proportion of patients responding to ifosfamide alone versus ifosfamide-cisplatin therapy was (0.36 versus 0.54) overall, 0.47 versus 0.61 for pelvic, 0.21 versus 0.54 for lung, and 0.33 versus 0.40 for 'other' metastatic sites of measurable disease. The relative odds ratio of response adjusted for measurable sites of disease was 1.82 (P = 0.03, one-tailed test; 95% lower confidence limit, 1.06). Progression-free survival (PFS) and survival data suggest that the combination offers a slight prolongation of PFS (relative risk, 0.73; 95% upper confidence limit, 0.94; P = 0.02, one-tailed test), but no significant survival benefit (relative risk, 0.80, 95% upper confidence limit, 1.03; P = 0.071, one-tailed test). Conclusion. The addition of cisplatin to ifosfamide appears to offer a small improvement in progression-free survival over ifosfamide alone in the management of advanced carcinosarcoma of the uterus; the added toxicity may not justify the use of this combination. (C) 2000 Academic Press.
AB - Objective. The aims of this study were to substantiate the previously reported activity of ifosfamide in patients with advanced, persistent, or recurrent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determine whether the addition of cisplatin results in an improved response or survival. Secondarily, we sought to determine the toxicity of ifosfamide-cisplatin in this patient population. Methods. Patients were randomized to receive ifosfamide (1.5 g/m2/day) times 5 days every 3 weeks for eight courses with mesna uroprotection, with or without cisplatin (20 mg/m2/day) times 5 days. No patient had received previous chemotherapy. Results. Of 224 patients entered on this study, 30 were ineligible for a variety of reasons, leaving 194 evaluable patients. Early in the study, the dose of the combination regimen was reduced by 20% (1 day) because of toxicity. The investigational arms were balanced for age, grade, and Gynecologic Oncology Group performance status. Percentages, of adverse effects reported in 191 patients receiving chemotherapy included (ifosfamide/cisplatin-ifosfamide) grade 3 or 4 granulocytopenia (36/60), grade 3 or 4 anemia (8/17), grade 3 or 4 central nervous system toxicity (19/14), and grade 3 or 4 peripheral neuropathy (1/12). Treatment may have contributed to the deaths of 6 patients treated with full doses of ifosfamide and cisplatin for 5 days. The proportion of patients responding to ifosfamide alone versus ifosfamide-cisplatin therapy was (0.36 versus 0.54) overall, 0.47 versus 0.61 for pelvic, 0.21 versus 0.54 for lung, and 0.33 versus 0.40 for 'other' metastatic sites of measurable disease. The relative odds ratio of response adjusted for measurable sites of disease was 1.82 (P = 0.03, one-tailed test; 95% lower confidence limit, 1.06). Progression-free survival (PFS) and survival data suggest that the combination offers a slight prolongation of PFS (relative risk, 0.73; 95% upper confidence limit, 0.94; P = 0.02, one-tailed test), but no significant survival benefit (relative risk, 0.80, 95% upper confidence limit, 1.03; P = 0.071, one-tailed test). Conclusion. The addition of cisplatin to ifosfamide appears to offer a small improvement in progression-free survival over ifosfamide alone in the management of advanced carcinosarcoma of the uterus; the added toxicity may not justify the use of this combination. (C) 2000 Academic Press.
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U2 - 10.1006/gyno.2000.6001
DO - 10.1006/gyno.2000.6001
M3 - Article
C2 - 11063636
AN - SCOPUS:0033766917
SN - 0090-8258
VL - 79
SP - 147
EP - 153
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -