Phase I study of 90Y-CC49 monoclonal antibody therapy in patients with advanced non-small cell lung cancer: effect of chelating agents and paclitaxel co-administration.

Academic Article

Abstract

  • PURPOSE: This trial was designed to evaluate strategies to improve the efficacy of a radiolabeled monoclonal antibody (mCC49) against tumor-associated glycoprotein-72 (TAG-72) in patients with non-small cell lung cancer (NSCLC). The aims of this study were to determine: safety and maximum tolerated dose (MTD) of (90)Y-mCC49 in combination with interferon alpha2beta (IFN); whether calcium disodium versonate (EDTA) or diethylenetriamine penta-acetic acid (DTPA) could reduce myelosuppression; and safety and MTD of paclitaxel (Taxol) in combination with (90)Y-mCC49. EXPERIMENTAL DESIGN: Patients with advanced (TAG-72 positive) non-small cell lung cancer were entered in three phases; the first was the dose escalation of a single agent (90)Y-mCC49. In the second phase, the dose escalation of (90)Y-mCC49 was attempted with concurrent EDTA or DTPA chelator therapy. In the third phase, radiosensitization with a continuous infusion of paclitaxel (96-hour) was administered with (90)Y-mCC49. All patients received IFN for TAG-72 up-regulation. RESULTS: Thirty-four patients were evaluable. Reversible Grade 4 neutropenia and thrombocytopenia were the dose-limiting toxicities (DLTs). The MTD of (90)Y-mCC49/IFN was 14 mCi/m(2). EDTA did not alter toxicity, while there was a modest reduction of myelosuppression with DTPA. The MTD of continuous infusion paclitaxel in combination with 14 mCi/m(2) of (90)Y-CC49 was 60 mg/m(2). There were no objective tumor responses. CONCLUSIONS: (90)Y-mCC49/IFN was well tolerated at a dose of 14 mCi/m(2). The clinical effect of adjunctive chelating therapy with DTPA was modest. The MTD of coadministered continuous infusion (96-hour) paclitaxel was 60 mg/m(2). Because of the immunogenicity of the murine compound, future studies are planned using a humanized version of CC49.
  • Keywords

  • Adult, Aged, Antibodies, Monoclonal, Antibodies, Neoplasm, Antigens, Neoplasm, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Chelating Agents, Clinical Trials as Topic, Disease Progression, Edetic Acid, Female, Glycoproteins, Humans, Lung Neoplasms, Male, Maximum Tolerated Dose, Middle Aged, Neutropenia, Paclitaxel, Pentetic Acid, Radioimmunotherapy, Radiometry, Thrombocytopenia, Treatment Outcome, Up-Regulation, Yttrium Radioisotopes
  • Digital Object Identifier (doi)

    Author List

  • Forero A; Meredith RF; Khazaeli MB; Shen S; Grizzle WE; Carey D; Busby E; LoBuglio AF; Robert F
  • Start Page

  • 467
  • End Page

  • 478
  • Volume

  • 20
  • Issue

  • 5