Phase II trial of intraperitoneal cisplatin with intravenous doxorubicin and cyclophosphamide in previously untreated patients with advanced ovarian cancer-long-term follow-up

Forty-three patients with ovarian cancer were entered on this trial and tre ated with intravenous (iv) cyclophosphamide (C) and doxorubicin (A), and in traperitoneal tip) cisplatin (DDP), every 21 days for eight cycles. Followi ng iv hydration, the cisplatin was administered through an intraperitoneal catheter in 2 L of 0.9% normal saline with a 4-h dwell. All patients are ev aluable for overall and progression-free survival with a median follow-up o f 70 months (range: 3-162 months); 39 patients are evaluable for response. All complete responses were surgically confirmed. The median age was 59 (ra nge 28-82 years); 3 patients were stage IC, 5 were IIC, 14 patients were st age III (optimally debulked), 14 patients were stage III (suboptimally debu lked), and 7 patients were stage IV. Two patients had received prior alkyla tor therapy. Six of 8 patients with Stage IC or II remain without evidence of disease at a mean of 12 years following chemotherapy. Of 14 optimally de bulked stage III patients, there were 7 complete responses, 3 partial respo nses, 1 patient with stable disease, and 3 inevaluable patients. Of 14 subo ptimally debulked stage III patients there were 4 complete responses, 4 par tial responses, 3 with stable disease, 2 progressions on treatment, and 1 i nevaluable patient. Five-year progression-free and overall survivals for st age III optimally debulked patients are 21 and 64%, respectively. At 10 yea rs, progression-free and overall survivals for this group are 21 and 299b, respectively. Toxicity included neutropenia (complicated by sepsis in 2 pat ients), infrequent thrombocytopenia, and mild anemia. Three patients develo ped transient serum creatinine elevations >2.0 mg/dl; however, decreased cr eatinine clearance was noted in 93/258 (36%) of evaluable courses which req uired a cisplatin dose reduction per protocol. Controllable hypomagnesemia, nausea, and emesis were also observed. We conclude that the combination of iv CA and ip DDP is an effective regimen with long-term progression-free a nd overall survivals that compare favorably with those of other published s tudies of intravenous or intraperitoneal chemotherapy. This report is unusu al in terms of the prolonged follow-up for all patients enrolled. These lon g-term results lend further support to recently published trials documentin g the efficacy of intraperitoneal chemotherapy for patients with this disea se. (C) 1999 Academic Press.