Intraperitoneal radioimmunochemotherapy of ovarian cancer: a phase I study.
A phase I trial was designed to examine the feasibility of combining interferon and Taxol with intraperitoneal radioimmunotherapy (177Lu-CC49). Patients with recurrent or persistent ovarian cancer confined to the abdominal cavity after first line therapy, Karnofsky performance status > 60, adequate liver, renal and hematologic function, and tumor that reacted with CC49 antibody were enrolled. Human recombinant alpha interferon (IFN) was administered as 4 subcutaneous injections of 3 x 10(6) U on alternate days beginning 5 days before RIT to increase the expression of the tumor-associated antigen, TAG-72. The addition of IFN increased hematologic toxicity such that the maximum tolerated dose (MTD) of the combination was 40 mCi/m2 compared to 177Lu-CC49 alone (45 mCi/m2). Taxol, which has radiosensitizing effects as well as antitumor activity against ovarian cancer, was given intraperitoneally (i.p.) 48 hrs before RIT. It was initiated at 25 mg/m2 and escalated at 25 mg/m2 increments to 100 mg/m2. Subsequent groups of patients were treated with IFN + 100 mg/m2 Taxol + escalating doses of 177Lu-CC49. Three or more patients were treated in each dose group and 34 patients were treated with the 3-agent combination. Therapy was well tolerated with the expected reversible hematologic toxicity. The MTD for 177Lu-CC49 was 40 mCi/m2 when given with IFN + 100 mg/m2 Taxol. Interferon increased the effective whole body half-time of radioactivity and the whole body radiation dose. Taxol did not have a significant effect on pharmacokinetic or dosimetry parameters. Four of 17 patients with CT measurable disease had a partial response (PR) and 4 of 27 patients with non-measurable disease have progression-free intervals of 18+, 21+, 21+, and 37+ months. The combination of intraperitoneal Taxol chemotherapy (100 mg/m2) with RIT using 177Lu-CC49 and interferon was well tolerated, with bone marrow suppression as the dose-limiting toxicity.
Meredith
R F
RF
Department of Radiation Oncology, University of Alabama at Birmingham, Comprehensive Cancer Center, Wallace Tumor Institute-117, 1530 3rd Avenue South, Birmingham, AL 35294-6832, USA. rmeredith@uabmc.edu
Alvarez
R D
RD
Partridge
E E
EE
Khazaeli
M B
MB
Lin
C Y
CY
Macey
D J
DJ
Austin
J M
JM
Kilgore
L C
LC
Grizzle
W E
WE
Schlom
J
J
LoBuglio
A F
AF
D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007370:Interferon Type I / Q000008:administration & dosage / Q000493:pharmacokinetics; D008187:Lutetium / Q000627:therapeutic use; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000493:pharmacokinetics; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use; D011877:Radionuclide Imaging; D011994:Recombinant Proteins; D016896:Treatment Outcome
D000912:Antibodies, Neoplasm; C091202:B72.3 antibody; D007370:Interferon Type I; D011868:Radioisotopes; D011994:Recombinant Proteins; D008187:Lutetium; D017239:Paclitaxel