Radioimmunotherapy with rhenium-186-labeled chimeric monoclonal antibody U36 in patients with head and neck squamous cell carcinoma

D. R. Colnot, J. J. Quak, R. De Bree, J. C. Roos, A. J. Wilhelm, G. B. Snow, G. A M S Van Dongen

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Despite improvements in locoregional treatment of stages III/IV squamous cell carcinoma of the head and neck (HNSCC), the local failure rate and the incidence of distant metastases in these advanced stages is high. This might be due to remaining small tumor lesions or micrometastases at the time of primary treatment, i.e. minimal residual disease. Therefore, an effective adjuvant systemic therapy is urgently needed for this group of patients. The use of radiolabeled monoclonal antibodies (MAbs) seems to be an attractive option due to the intrinsic radiosensitivity of HNSCC and the selectivity of MAbs. At our department several MAbs directed against antigens selectively expressed by HNSCC have been developed. One of these, cMAb U36, targets 99% of primary tumors as well as metastatic HNSCC and shows a homogeneous reactivity pattern. By coupling the radionuclides 99mTc and 186Re in a similar way to cMAb U36, conjugates were developed for diagnostic and therapeutic application, respectively. To evaluate its safety and to establish a maximum tolerated dose, a phase I dose escalation study was performed with 186Re-cMAb U36 in HNSCC patients for whom no curative options were available. A total of 13 patients were treated with doses of 11, 27 and 41 mCi/m2. One week prior to therapy, a diagnostic study with 99mTc-cMAb U36 was done. Imaging during therapy showed excellent targeting of tumor recurrences and distant metastases in all patients. A grade IV myelotoxicity was seen in 2 patients treated at the highest dose level. In these 2 patients anti-tumor effects were observed in bulky tumor masses. No other toxicities were observed. These observations justify further development of radioimmunotheMpy with 186Re-cMAb U36 as an adjuvant treatment for eradication of minimal residual HNSCC.

Original languageEnglish
Number of pages1
JournalActa oto-rhino-laryngologica belgica
Issue number4
Publication statusPublished - 1 Dec 1999

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