J H Edmonson

PURPOSE: This three-armed phase III study in adults with advanced soft tissue sarcomas was planned as a comparison of objective regression rates, toxicity, and survival of patients receiving doxorubicin alone, ifosfamide plus doxorubicin, and mitomycin plus doxorubicin plus cisplatin. PATIENTS AND METHODS: Between December 1987 and July 1990, 279 patients with histologically confirmed sarcomas were enrolled to receive treatment A (doxorubicin 80 mg/m2), treatment B (ifosfamide 7.5 g/m2 plus doxorubicin 60 mg/m2), or treatment C (mitomycin 8 mg/m2 plus doxorubicin 40 mg/m2 plus cisplatin 60 mg/m2). RESULTS: Of 262 assessable patients, 74 (29%) achieved objective tumor regression. Objective regression occurred in 20% of the 90 patients who received doxorubicin alone (complete remission [CR] rate, 2%), in 34% of the 88 who received ifosfamide plus doxorubicin (CR rate, 3%), and in 32% of the 84 who received mitomycin plus doxorubicin plus cisplatin (CR rate, 7%). With grade 3 or greater myelosuppression in 53% of group A, 80% of group B, and 55% of group C, regimen B was significantly more myelosuppressive than either regimen A or C (P = .01) with two, three, and one treatment-related deaths, respectively. Synovial sarcomas were responsive to ifosfamide plus doxorubicin, especially among patients younger than 40 years of age. CONCLUSION: Ifosfamide plus doxorubicin produced a significantly higher regression rate (P = .03) than did doxorubicin alone; however, this was achieved at a level of myelosuppression significantly more intense than that produced by the single agent or by the three-drug combination. Mitomycin, doxorubicin, and cisplatin also appeared to be more active than the single agent; however, at a myelosuppression level similar to that of doxorubicin alone, this trend (P = .07) did not attain the usual level for significance. No significant survival differences were observed.

PURPOSE: To evaluate the prognostic significance of p53 expression in epithelial ovarian cancer, including a subset of stage I patients, and to look for correlations between p53 expression and other disease parameters, including stage, grade, age, histologic subtype, second-look results, ploidy, and percent S phase. PATIENTS AND METHODS: We analyzed p53 expression in 284 patients with epithelial ovarian cancer using immunohistochemical techniques in paraffin-embedded specimens. There were 36 patients with stage I disease, 20 with stage II disease, 186 with stage III disease, and 42 with stage IV disease. RESULTS: p53 immunoreactivity was present in 177 cases (62%). p53 expression was associated with grade 3 to 4 disease (P = .003). The following factors were associated with a decrease in overall survival in a univarate analysis: stage III or IV disease (P = .0001), grade 3 or 4 disease (P = .0001), age above the median (P = .0002), and p53 reactivity (P = .04). In a multivariate analysis, stage, grade, and age retained independent prognostic significance. In the subset of 36 stage I patients, p53 positively approached statistical significance (P = .10) as a negative prognostic factor in a univariate analysis. CONCLUSION: Abnormalities of p53 expression occur commonly in epithelial ovarian cancer. Although associated with decreased survival in a univariate analysis, this biologic marker did not retain independent prognostic significance in a multivariate analysis. p53 expression should be studied in a larger cohort of early-stage patients, where accurate prognostic information is needed to direct therapy.