A randomized, prospective GOG study (Protocol 104) of intraperitoneal cisplatin versus intravenous cisplatin (100 mg/m2), each given with 750 mg/m2 cyclophosphamide, was performed jointly by the SWOG and the GOG in patients with minimal residual disease (212). The intraperitoneal cisplatin arm had a somewhat longer overall median survival than the intravenous arm, 49 versus 41 months (p = 0.03). In the patients with minimal residual disease (<0.5 cm maximal residual), paradoxically, there was no difference between the two treatments, 51 versus 46 months (p = 0.08).
In a follow-up GOG study (Protocol 114), the dose-intense arm was initiated by giving a moderately high dose of carboplatin (dose AUC = 9) for two induction cycles, followed by intraperitoneal cisplatin 100 mg/m2 and intravenous paclitaxel 135 mg/m2 over 24 hours, versus intravenous cisplatin 75 mg/m2 and intravenous paclitaxel 135 mg/m2 (213). The dose-intense arm results were slightly better—the disease progression-free median survival was 27.6 months compared with 22.5 months for the control arm (p = 0.02). There was no difference in overall survival (52.9 months versus 47.6 months, p = 0.056). Based on this study, it was unclear whether dose intensification with intraperitoneal cisplatin has a sustained long-term impact on the survival of these patients.
A third randomized prospective GOG study (Protocol 172) compared intraperitoneal cisplatin and paclitaxel versus intravenous cisplatin and paclitaxel (214). The combination of cisplatin 75 mg/m2 and paclitaxel 135 mg/m2 given intravenously every 3 weeks was compared with paclitaxel 135 mg/m2 intravenous day 1, followed by cisplatin 100 mg/m2 intraperitoneal day 2, and paclitaxel 60 mg/m2 intraperitoneal day 8 every 3 weeks, each given for six cycles.
Although 83% of the patients randomized to intravenous chemotherapy completed all six cycles of therapy, only 42% of those treated with intraperitoneal chemotherapy completed the six cycles, principally because of catheter-related complications. For patients in either group who could not complete the therapy because of cisplatin-related toxicity, the chemotherapy was switched to intravenous carboplatin. Comparing the intravenous and intraperitoneal arms, the median duration of progression-free survival was 18.3 and 23.8 months, respectively (p = 0.05). The median duration of overall survival in the intravenous-therapy and intraperitoneal-therapy groups was 49.7 and 65.6 months, respectively (p = 0.03) (214). Quality of life was significantly worse in the intraperitoneal-therapy group before cycle four and 3 to 6 weeks after treatment but not 1 year after treatment. A summary of the intraperitoneal catheter-related issues in this trial was presented (215).