title: Variable low dose rate irradiation (131I-anti-CEA) and integrated low dose chemotherapy in the treatment of nonresectable primary intrahepatic cholangiocarcinoma.
abstract: Previous experience using 131I anti-CEA antibody, which irradiates at a variable low dose rate in combination with a multimodality treatment program, has demonstrated acceptable toxicity and response in primary intrahepatic cholangiocarcinoma. In attempting to improve therapy, Cis-platin was added to the prior regimen. Induction therapy was unchanged. One month later, chemotherapy was given (doxorubicin, 15 mg, 5-fluorouracil, 500 mg, plus Cis-platin, 20 mg/M2) followed the next day by outpatient administration of 20 mCi 131I anti-CEA by i.v. bolus. Five days later, 10 mCi was administered. The latter regimen (chemotherapy plus 20 + 10 mCi 131I anti-CEA) was repeated every 2 months using polyclonal antibodies derived from different species (rabbit, pig, baboon, and horse). Twenty-four patients (29% with prior chemotherapy and/or metastases) were prospectively treated according to this regimen. Toxicity was limited to hematologic toxicity and was manifested by thrombocytopenia and leukopenia (17% and 4% grade 4, respectively, according to RTOG toxicity criteria). Tumor remission was evaluated by CT volumetric analysis and demonstrated a 14% response rate for the induction portion of therapy, 24% for the radioimmunoglobulin portion of treatment, and 50% remission rate when all subsequent tumor volumes were compared to the pre-treatment volume (entire program). The median survival for the entire group of patients was 10.1 months. This result is superior to previously reported trials and, in comparison to our previous study (10.1 vs 6.5 months median survival), further advancement in protocol design appears to have been made. In view of the rarity of this disorder, a randomized trial is not possible and strict statistical analyses cannot be made. The mechanism of 131I-anti-CEA variable low dose irradiation and chemotherapy interaction is discussed as well as further potential modifications for treatment improvement.
authors.affiliation: Department of Radiation Oncology, Johns Hopkins Hospital, Baltimore, MD 21205.
authors.forename: G B
authors.initials: GB
authors.lastname: Stillwagon
authors.forename: S E
authors.initials: SE
authors.lastname: Order
authors.forename: T
authors.initials: T
authors.lastname: Haulk
authors.forename: J
authors.initials: J
authors.lastname: Herpst
authors.forename: D S
authors.initials: DS
authors.lastname: Ettinger
authors.forename: E K
authors.initials: EK
authors.lastname: Fishman
authors.forename: J L
authors.initials: JL
authors.lastname: Klein
authors.forename: P K
authors.initials: PK
authors.lastname: Leichner
mesh_terms: D002759:Adenoma, Bile Duct / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy; D016019:Survival Analysis
chemical_list: D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes; D002945:Cisplatin