title: Safety and Outcome Measures of First-in-Human Intraperitoneal α Radioimmunotherapy With 212Pb-TCMC-Trastuzumab.
abstract: One-year monitoring of patients receiving intraperitoneal (IP) Pb-TCMC-trastuzumab to provide long-term safety and outcome data. A secondary objective was to study 7 tumor markers for correlation with outcome.
  
  
  
  Eighteen patients with relapsed intra-abdominal human epidermal growth factor receptor-2 expressing peritoneal metastases were treated with a single IP infusion of Pb-TCMC-trastuzumab, delivered <4 h after 4 mg/kg IV trastuzumab. Seven tumor markers were studied for correlation with outcome.
  
  
  
  Six dose levels (7.4, 9.6, 12.6, 16.3, 21.1, 27.4 MBq/m) were well tolerated with early possibly agent-related adverse events being mild, transient, and not dose dependent. These included asymptomatic, abnormal laboratory values. No late renal, liver, cardiac, or other toxicity was noted up to 1 year. There were no clinical signs or symptoms of an immune response to Pb-TCMC-trastuzumab, and assays to detect an immune response to this conjugate were negative for all tested. Tumor marker studies in ovarian cancer patients showed a trend of decreasing Cancer antigen 72-4 (CA 72-4) aka tumor-associated glycoprotein 72 (TAG-72) and tumor growth with increasing administered radioactivity. Other tumor markers, including carbohydrate antigen (CA125), human epididymis protein 4 (HE-4), serum amyloid A (SAA), mesothelin, interleukin-6 (IL-6), and carcinoembryonic antigen (CEA) did not correlate with imaging outcome.
  
  
  
  IP Pb-TCMC-trastuzumab up to 27 MBq/m seems safe for patients with peritoneal carcinomatosis who have failed standard therapies. Serum TAG-72 levels better correlated to imaging changes in ovarian cancer patients than the more common tumor marker, CA125.
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Ruby F
authors.initials: RF
authors.lastname: Meredith
authors.affiliation: AREVA Med, Plano, TX.
authors.forename: Julien J
authors.initials: JJ
authors.lastname: Torgue
authors.affiliation: AREVA Med, Plano, TX.
authors.forename: Tania A
authors.initials: TA
authors.lastname: Rozgaja
authors.affiliation: AREVA Med, Plano, TX.
authors.forename: Eileen P
authors.initials: EP
authors.lastname: Banaga
authors.affiliation: Gynecology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Patty W
authors.initials: PW
authors.lastname: Bunch
authors.affiliation: Gynecology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Alvarez
authors.affiliation: Gynecology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Straughn
authors.affiliation: Departments of Radiation Oncology.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Dobelbower
authors.affiliation: Department of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California, San Diego, CA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lowy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000074322:Antineoplastic Agents, Immunological / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017879:Isothiocyanates / Q000737:chemistry*; D007856:Lead Radioisotopes / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D017063:Outcome Assessment, Health Care; D010051:Ovarian Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D010534:Peritoneal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D016499:Radioimmunotherapy / Q000401:mortality*; D015996:Survival Rate; D000068878:Trastuzumab / Q000627:therapeutic use*
chemical_list: D000074322:Antineoplastic Agents, Immunological; D017879:Isothiocyanates; D007856:Lead Radioisotopes; C000615125:Lead-212; D000068878:Trastuzumab