Objectives.The aim of the current study is to evaluate the results of therapy with induction with weekly cisplatin followed by the combination of cisplatin–doxorubicin–cyclophosphamide (PAC) or the combination paclitaxel–cisplatin (TP) as first-line chemotherapy in patients with primary peritoneal adenocarcinoma (PPA).Methods.Between October 1988 and July 1996, 46 patients with PPA were treated with PAC (n= 25) or TP (n= 21) following cytoreductive surgery in two sequential trials. In trial 1, patients received induction with weekly cisplatin (1 mg/kg) × 4 followed by monthly cisplatin (50 mg/m2), cyclophosphamide (750 mg/m2), and doxorubicin (50 mg/m2) for 10 cycles. In trial 2, patients received induction with weekly cisplatin (1 mg/kg) × 4 followed by monthly cisplatin (75 mg/m2) and paclitaxel (135 mg/m2) over 24 hr for 6 cycles. Surgical assessment of response was performed in 15 (60.0%) and 13 (61.9%) patients in the PAC and TP trials, respectively. Estimated survival and progression-free survival distributions were calculated by the method of Kaplan and Meier. Survival curves were compared using the log rank test.Results.There were no significant differences between patients in either treatment arm with respect to median age, substage, percentage of patients undergoing optimal cytoreductive surgery, median preoperative CA125 values, performance status, proportion of patients who had second-look procedures, or median cumulative doses of cisplatin. The incidence of nausea and vomiting as well as peripheral neuropathy was significantly higher among patients who received TP (P= 0.005 and 0.022, respectively). The overall response, surgical response, and complete surgical response were not statistically different among patients who received PAC and those who received TP (62.5% versus 70.0%,P= 0.75, 73.3% versus 76.9%,P= 0.1, and 13.3% versus 23.1%,P= 0.64, respectively). Patients who underwent optimal cytoreductive surgery demonstrated higher response than patients whose tumors could not be optimally cytoreduced (76.7% versus 42.9%,P= 0.04). There was no statistically significant difference in overall survival or time to progression/recurrence between the PAC and TP groups (median 21.5 versus 24.0 months,P= 0.68, and 17.3 versus 24.0 months,P= 0.59, respectively). In both treatment groups combined, 18 of 32 patients whose tumors were optimally cytoreduced and 3 of 14 patients whose tumors were suboptimally cytoreduced had surgically verified response. Patients who underwent optimal cytoreductive surgery exhibited longer survival than those who underwent suboptimal cytoreductive surgery (median 29.4 versus 18.6 months,P= 0.008).Conclusions.Both PAC and TP regimens are effective combinations in patients with PPA. The median survival was similar following PAC and TP but the responses and time to recurrence/progression were nonsignificantly better in the paclitaxel combination.