A phase I trial of intraperitoneal carboplatin and etoposide with granulocyte macrophage colony stimulating factor support in patients with intraabdominal malignancies

Abstract

Background. Although somewhat controversial, there are data to suggest that patients with ovarian cancer may experience a survival advantage if the dose intensity of platinum‐containing regimens can be maximized. Administration of chemotherapeutic agents via the intraperitoneal route offers the opportunity to increase dose intensity of several chemotherapeutic agents. Methods. The authors conducted a Phase I trial of intraperitoneal carboplatin and etoposide in combination with granulocyte macrophage colony stimulating factor (GM‐CSF) in an attempt to determine the maximum tolerated dose of carboplatin. The starting dose for carboplatin was 300 mg/m2 and for etoposide 400 mg/m2. The dose of carboplatin was escalated while the etoposide was maintained at the initial dose. The total dose of each agent was calculated and given daily over 3 days in amounts equal to one‐third of the total dose. On day 1 of therapy, onethird of the dose was mixed in 2 liters of dextrose (D5 W) and administered intraperitoneally (IP) as rapidly as possible. On Days 2 and 3, one‐third of the dose was mixed in 1 liter of D5 W and administered similarly. GM‐CSF was begun on Day 4 as a subcutaneous injection at a dose of 500 mg/m2/d. Results Unacceptable hematologic toxicity was encountered at a carboplatin dose of 800 mg/m2; therefore, a carboplatin dose of 600 mg/m2 is recommended for Phase II studies. An overall response rate of 54% with a complete response rate of 17% was observed in patients with ovarian cancer. The overall response rate for all patients was 45%. Conclusion. Because of the significant toxicity encountered in this study, it is recommended that this regimen be used only in the context of a clinical study. The recommended Phase II study dose for this combination is carboplatin 600 mg/M2 and a total dose of etoposide 400 mg/M2 total dose given as three equal parts IP over 3 days. GM‐CSF should begin on Day 4 at a dose of 500 mg/m2/day subcutaneously and should continue until the absolute neutrophil count is greater than 1000 granulocytes on 3 successive days. Cancer 1994; 74: 664‐9

Principles and practice of intraperitoneal chemotherapy for ovarian cancer

“…Therefore, IP chemotherapy using platinum agents can be hypothesized as one route of systemic chemotherapy. Table 2 summarizes results of phase I trials with or without pharmacokinetic study (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) . Among those agents, this section will discuss the pharmacology of IP cisplatin, carboplatin, and paclitaxel including animal experiments.…”

“…Table 2 summarizes results of phase I trials with or without pharmacokinetic study (9–26) . Among those agents, this section will discuss the pharmacology of IP cisplatin, carboplatin, and paclitaxel including animal experiments.…”