Phase III Trial of Intraperitoneal Therapy With Yttrium-90–Labeled HMFG1 Murine Monoclonal Antibody in Patients With Epithelial Ovarian Cancer After a Surgically Defined Complete Remission

Abstract

After a median follow-up of 3.5 years (range, 1 to 6 years), 70 patients had died in the active treatment arm compared with 61 patients in the control arm. Cox proportional hazards analysis of survival demonstrated no difference between treatment arms. In the study drug arm, 104 patients experienced relapse compared with 98 patients in the standard treatment arm. No difference in time to relapse was observed between the two study arms. Active therapy was associated with occasional grade 3 or 4 thrombocytopenia and neutropenia and grade 1 or 2 GI symptoms, abdominal discomfort, arthralgia, and myalgia. CONCLUSION A single IP administration of 90Y-muHMFG1 to patients with EOC who had a negative SLL after primary therapy did not extend survival or time to relapse.

Pharmacokinetics and Imaging of212Pb-TCMC-Trastuzumab After Intraperitoneal Administration in Ovarian Cancer Patients

“…Intensification of treatment by intraperitoneal (IP) chemotherapy and/or radionuclides has shown therapeutic efficacy, and some Phase III studies have documented improved survival and/or decreased abdominal failure rate. 1,2 Much work remains to optimize the agents and their integration with other modalities to achieve improved outcome. Prior experience with IP radionuclide conjugate therapy suggests that a radionuclide with shorter half-life than the 2.7 days of 90 Y and less c emissions than 131 I or 177 Lu would allow dose escalation without excess toxicity.…”

The use of monoclonal antibodies for the treatment of epithelial ovarian cancer (review)

“…The first one by Nicholson et al (75) (78). Reported side-effects of ip HMFG1 were nausea, fatigue, arthralgia, myalgia, thrombocytopenia and neutropenia (78). Although there was no significant difference in time to relapse and overall survival in the SMART study, interestingly, there was a significant difference in pattern of disease recurrence (110).…”

“…Based on these promising results two phase III trials haven been undertaken. The first one by Nicholson et al (75) (78). Reported side-effects of ip HMFG1 were nausea, fatigue, arthralgia, myalgia, thrombocytopenia and neutropenia (78).…”

“…To date, 15 different antibodies have been used directed against 5 different tumor-associated antigens and one antiangiogenesis antigen (VEGF). Of the 44 clinical trials, 23 trials studied immunotherapy with unconjugated Mab (27,, five trials studied vaccination with Mabs (58-62), while 16 trials studied RIT (63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78). Two of the RIT trials used a combination of cytotoxic chemotherapy and RIT (64,71).…”

“…A combination of unconjugated Mabs combined with cytotoxic chemotherapy administration was assessed in four trials (43,47,53,57). Because of the high propensity to stay confined to the peritoneal cavity until very late in the course of the disease, many trials on radiolabeled Mab in ovarian cancer patients used the ip route for administration (19/44) (38,41,44,50,51,63,64,(66)(67)(68)(69)(70)(71)(73)(74)(75)(76)(77)(78). In 20 studies the Mab was administered iv (36,37,39,40,42,43,45-49,52-55,57,60,65,72,79), two studies injected im (59,61), while 2 other studies used both iv and ip routes of administration Table I.…”