ANDROGEN DEPRIVATION AND RADIATION-THERAPY - SEQUENCING STUDIES USINGTHE SHIONOGI IN-VIVO TUMOR SYSTEM

Purpose: To test the relative effect of neoadjuvant and adjuvant andro gen deprivation on the radiation response of an androgen dependent tum or, Methods and Materials: The transplantable, androgen dependent, Shi onogi adenocarcinoma was grown as allografts in the hind limbs of NCr/ Sed (nu/nu) athymic nude mice, Bilateral orchiectomy was the chosen fo rm of androgen deprivation, Groups of tumors were irradiated to graded tumor doses and then studied for durable tumor control. The radiation response was expressed as the radiation dose required to control 50% of the tumors (TCD50). The sequence of radiation and orchiectomy was s tudied, Results: When radiation was combined with orchiectomy the Shio nogi tumor was significantly more likely to be controlled than when ra diation was used alone, Orchiectomy 12 days prior to radiation (neoadj uvant therapy) produced a significantly greater decline in the TCD50 t han when orchiectomy was used 1 day or 12 days after radiation (adjuva nt therapy). If, before radiation, tumors were allowed to regrow after orchiectomy to their original size in an androgen independent fashion then the advantage was largely lost, Those tumors responding well to neoadjuvant orchiectomy (> 50% volume decrease) were significantly mor e likely to be eradicated by radiation than those with a lesser respon se, Conclusion: When using combinations of androgen deprivation and ra diation in the treatment of the Shionogi tumor, sequence and timing of the therapies are crucial to maximize the erect. (C) 1997 Elsevier Sc ience Inc.