Impact of monitoring plasma 1,1-dichlorodiphenildichloroethane (o,p ' DDD)levels on the treatment of patients with adrenocortical carcinoma

BACKGROUND. It has been suggested recently that 1,1-dichlorodiphenildichlor oethane (o,p'DDD) elicits a dose effect relation in the treatment of patien ts with adrenocortical carcinoma (ACC). The authors performed a single-cent er, prospective study with two major objectives: 1) to confirm the interest of plasma o,p'DDD level measurement as a prognostic factor of response to o,p'DDD therapy; and 2) to look for parameters associated with a therapeuti c plasma o,p'DDD level, especially the daily o,p'DDD dose. METHODS. Since 1995, patients with ACC who were referred to the Gustave-Rou ssy Institute have been enrolled prospectively in the study, Therapy with o ,p'DDD was given as first-line therapy in 13 patients with metastatic disea se or as adjuvant therapy in 11 patients. Oral o,p'DDD was given in three s eparate doses up to at least 6-12 g per day together with substitutive adre nal therapy. Plasma o,p'DDD levels were measured using high-performance liq uid chromatography every 2 months. The o,p'DDD therapy was monitored to ach ieve plasma o,p'DDD levels within 14-20 mg/L. World Health Organization cri teria were used to evaluate tumor response and toxicity. RESULTS. Twenty-four patients with ACC were studied, and a plasma o,p'DDD l evel > 14 mg/L was achieved in 14 patients (58%). An objective tumor respon se was observed in four patients with metastatic lesions (31%): One was res ponse was complete, and three were objective hormonal responses. These tumo r responses were observed among the six patients who achieved therapeutic p lasma o,p'DDD levels. In contrast, no response was observed among the seven patients with plasma o,p'DDD levels that remained consistently low. Eight of 11 patients who received o,p'DDD as adjuvant therapy had disease recurre nce, although the plasma o,p'DDD level was > 14 mg/L in 6 patients. Grade 3 or 4 neurologic toxicity was observed in three patients (12%), all with an o,p'DDD level > 20 mg/L. The daily o,p'DDD dose was the only parameter ass ociated with the highest plasma c,p'DDD trough levels: It explained 35% of the variability in the plasma o,p'DDD level. A median interval of 3.7 month s was found necessary to achieve the highest o,p'DDD trough levels. CONCLUSIONS. The results confirm the prognostic impact of the plasma o,p'DD D level in patients with metastatic ACC and its interest in avoiding toxici ty. Cancer (C) 2001 American Cancer Society.