>BEC Abstracts from www.rationaltherapeutics.com. Dr. Nagourneys
>page
>#1070 BEC, A Mixture Of Solasodine Glycosides Reveals Cytotoxic
>Activity In Human Tumor Primary Culture Specimens: Pre-Clinical And
>Early Clinical Observations: YZ Su, DG Spall, MA Traill, C Kollin, C
>Chow, B. Sommers, S. Harper, D Horlick, SS Evans and RA Nagourney.
>Rational Theraputics, Inc. Long Beach, CA 90806 and OncoCare Cancer
>and Prostcare Clinic, Melbourne Australia.
>
>BEC, a mixture of glycoalkaloids extracted from Solanum Sodomaeum
>has shown activity in human tumor cell lines (Cham, BE. Canc. Lett.
>55:1990). To characterize the cytotoxicity of BEC for human tumors
>we applied an ex vivo cell death assay (EVA) in 23 fresh human tumor
>specimens. These included 8 Gynecologic (Gyn); 6 GI; 2 NSCLC; 2
>Breast (Bre) & 2 Sarcomas (Sar). In addition BEC activity was
>compared with other cytotoxic agents, including Cisplatin (CDDP);
>Doxorubicin (Dox), Paclitaxel (P); Nitrogen Mustard (NM);
>Vinorelbine (V); Topotecan (T); Etoposide (E); Gemcitabine (Gem) and
>Arsenic Trioxide (ARS). IC50 results for all 23 studies revealed a
>Median of 8.8 ug/ml and a Mean of 8.6 +/- 1 ug/ml (SEM). Mean IC50
>(ug/ml) by tumor type revealed Sar = 3.1; GI = 6.3; Bre = 7.8; Gyn =
>9.6; NSCLC = 14.5. A comparison of Mean IC50 values for BEC against
>other drugs revealed correlation coefficients (R values) for NM of
>0.76 (p<0.001) and for Gem of 0.45 (p<0.05) but no correlation with
>T, E, CDDP, P, V or ARS. Under Australian Special Access
>Experimental Drug Use Guidelines, 8 patients have received IV
>infusions of BEC at doses of 50 mg/m2 to 125 mg/m2, daily X 5 for 2
>weeks/month, for a total of 10 cycles to date. Toxicities have
>included rigors, fever, chemical phlebitis and reversible elevations
>of the transaminases. No hematologic, renal, cardiac or neurological
>toxicities were observed. Dose escalations and assessments of
>response continue. Conclusions: BEC reveals cytotoxic activity in
>human tumors. The ex vivo activity profile of BEC correlates with NM
>& Gem. Preliminary results indicate that BEC can be administered IV
>at up to 125 mg/m2. Cell death assays provide drug and disease
>specific information that can streamline novel agent development.
>Supported by The Vanguard Cancer Foundation and the Tina Robinson
>Cancer Research Fund.
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