A phase I trial of intraperitoneal recombinant gamma-interferon in advanced ovarian carcinoma.

Abstract

The interferons are a class of biological agents that have demonstrated antineoplastic activity in a variety of tumors both in vitro and in vivo. Previous reports have suggested that interferons can be safely administered by the intraperitoneal (IP) route with a pharmacokinetic advantage for peritoneal cavity exposure compared with the systemic circulation and with objective antitumor activity being demonstrated. On the basis of these reports and laboratory data suggesting activity for recombinant gamma-interferon (r-GIFN) against several malignant cell lines, we treated 27 refractory ovarian carcinoma patients, including six with very-small-volume residual disease, with this agent delivered by the IP route. While r-GIFN was found to be remarkably well tolerated, with a 150- to 200-fold pharmacokinetic advantage for peak levels achieved in the peritoneal cavity compared with the plasma, no objective responses were observed. Despite the lack of demonstrated activity for single-agent IP-administered r-GIFN in this clinical setting, there remains considerable interest in this agent when delivered by the IP route because of in vitro data suggesting concentration-dependent synergy between r-GIFN and other biological agents.

Suppression by interferon-? of tumor cell-induced increase in mesothelial permeability

“…Many investigations have been performed on the effects of IFN-y on tumor metastasis and invasion [9][10][11][12]. Moreover, clinical trials of intraperitoneal administration of IFN-), for malignant ascites have recently been reported by some investigators [13,14]. However, it remains unclear how IFN-y affects the interaction of tumor cells with peritoneal mesothelial cells, considered to be the initial step of peritoneal metastasis [1][2][3][4].…”

Activation of peritoneal macrophages in patients with gynecological malignancies by sizofiran and recombinant interferon-γ

“…It was effective in murine tumor systems when dosed locally for intraperitoneally implanted tumors [19]. Reportedly, rIFN-y did not show any antitumor effect in patients with ovarian cancer, but it was well tolerated with significant intraperitoneal levels being maintained beyond 24 hours [20]. Thus, in the present study to treat ovarian cancer we used the intraperitoneal route for rIFN-y administration.…”

“…Thus, in the present study to treat ovarian cancer we used the intraperitoneal route for rIFN-y administration. rIFN-7 has been reported to be highly safe at doses of 0.5 -2.0 x 106Iu/ma/weeks for as long as 24 weeks, although accompanied with varying degrees of some commonly reported side effects (overall incidence:54%) such as fever and flulike symptoms [20]. We selected a dose of 2 • 106IU rIFN-y/body, equivalent to 1.3 to 1.5 x 106IU/m 2, expecting good tolerance and sufficient efficacy.…”

Immunologische und innovative Therapieformen beim Ovarialkarzinom

“…In einer anderen Phase I-Studie wurde die intraperitonale Applikation von Interferon-g ohne antineoplastische Wirkung beschrieben [2].…”