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369In summary, the findings of this investigation support the concurrent validity of many of the MMPI scales for DSM-I11 personality disorders. The failure of some MMPI scales to show adequate convergent validity is probably due to inappropriate criterion measures. Of course, the results of this study are based on a relatively small sample of psychiatric patients and need to be replicated on other populations that have higher representations of outpatients. Also, because patients were referred for psychological testing, they may constitute a sample of more "difficult" or "interesting" patients. This limitation should be kept in mind when conclusions are drawn from these results. In addition, other external criterion measures should be utilized in order to advance the validity of both the MMPI and MCMI personality disorder scales.

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3048 Background: E7820 is a first-in-class oral antiangiogenic sulfonamide that inhibits alpha-2 integrin expression, endothelial cell proliferation and is active against human breast and pancreatic cancer xenografts. Methods: The objectives of the study were to evaluate the safety, tolerability, to determine the maximum tolerated dose (MTD) to characterize the PK behavior, to assess PD markers and to explore the antitumor activity. Results: Thirty pts (18 male/12 female; age range 40–83) received E7820 at doses ranging from 10 to 200 mg daily continuously, in a 28 day cycle. A total of 93 cycles were administered (range 1–15); 4 pts underwent intrapatient dose escalation. Dose-limiting toxicities (DLT) at 100 mg/day included grade (gr) 3 elevated liver enzymes and gr 3 hemoptysis. At the 200 mg dose level, 2 pts experienced hematological toxicity, including gr 4 thrombocytopenia and neutropenia. One of these patients with cervical cancer and a vaginal fistula had gr 4 thrombocytopenia, neutropenia and gr 3 anemia with a fatal bleed from her pelvic tumor. Other gr 3/4 adverse events included: nausea, vomiting, fatigue, hypoxia, chest pain, abdominal pain, ileus, anemia, neutropenia, hypoalbuminemia, elevated transaminases and alkaline phosphatases. Disease stabilization beyond cycle 4 was observed in 6 pts, with 3 lasting for 6+ months. Tmax ranged from 1.3–5.3 hr and the t1/2 is 5.7 to 11.9 hr. Cmax and AUC increased dose proportionaly up to 70 mg, however accumulation was seen at 200 mg. At higher doses (70–200 mg) plasma concentrations exceed levels active in preclinical models in vivo. Preliminary analysis of alpha-2 integrin expression showed marked (∼50%) and sustained decreases beyond day 28 in 3 of 4 pts at 200 mg, while moderate (<30%) and less consistent decreases were observed in 2/3 and 3/6 pts at 70 mg and 100 mg dose levels, respectively. No changes in integrin levels were observed at E7820 doses < 40 mg. Conclusions: Up to 100 mg/day E7820 has a good safety profile in pts with solid malignancies. MTD was established at 100 mg/day. Patient treatment and PD analyses are ongoing. [Table: see text]

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