BioOncology Watch Timely Information for Practicing Physicians
JULY 1999 Highlights from the Annual Meeting of the American Society of Clinical Oncology NON-HODGKIN'S LYMPHOMA (NHL) BCL-2 antisense molecule. Justin Waters and colleagues conducted a phase I trial in which the BCL-2 antisense agent G3139 (Genta Inc.) was well tolerated as a 14 day subcutaneous infusion in 21 previously treated NHL patients. BCL-2 protein was reduced in 5 of 12 patients and 1 complete, 1 minor, and 9 stable disease responses were achieved, indicating that BCL-2 antisense has potential anti-tumor activity. (Waters JS, et al. Proc Am Soc Clin Onc 1999; 18: 4a, abstract 11) Combination Rituxan® and fludarabine. Myron Czuczman et al. presented preliminary results from a pilot study of Rituxan combined with fludarabine in 10 NHL patients (6 naïve, 4 previously treated). While there is no reported preclinical or clinical supportive data, the sample size is small, and the results are early, 9 patients responded after 3 cycles (1CR and 8 PRs). Significant cytopenias were observed. (Czuczman MS, et al. Proc Am Soc Clin Onc 1999; 18: 17a, abstract 61) Radioiodinated anti-Cd 20 antibody. A. Gopal and coworkers reported durable remissions in 5 patients with an aggressive poor prognostic variant of NHL (mantle cell lymphoma) after treatment with high dose I-131-anti-Cd20 antibody (anti-B1, Coulter Pharmaceutical, Inc.) combined with cyclophosphamide, etoposide, and autologous stem cell transplantation. A larger sample size is needed, but all 5 patients remain free of progression after a median follow-up of 23 months (range 4-29 months). (Gopal A, et al. Proc Am Soc Clin Onc 1999; 18: 16a, abstract 54) CHRONIC MYELOGENOUS LEUKEMIA (CML) ABL tyrosine kinase inhibitor. B.J. Druker and associates presented phase I data that indicate chronic phase CML patients who have previously failed interferon therapy may benefit from treatment with a specific inhibitor of BCR-ABL tyrosine kinase activity (CGP 57148, Novartis Pharmaceuticals). A daily oral administration achieved adequate plasma concentrations and was well tolerated. Decreases in white blood cell counts, including 2 complete hematologic responses, were seen. (Druker BJ, et al. Proc Am Soc Clin Onc 1999, 18: 7a, abstract 24) ACUTE MYELOGENOUS LEUKEMIA (AML) Humanized monoclonal anti-CD33 antibody. E. Feldman and colleagues reported that treatment of 35 relapsed/refractory AML patients at two dose levels of a monoclonal anti-CD33 antibody (HuM195, Protein Design Labs, Inc.) has biological activity and appears to be safe. Few adverse events were reported in this 35 patient study and 2 CRs were observed at the lower dose level. Grade 3 and 4 hematological toxicity was seen, but it was unclear if it was related to therapy and 1 patient had an anaphylactic event. (Feldman E, et al. Proc Am Soc Clin Onc 1999; 18: 4a, abstract 12) Antigen-targeted chemotherapy. Eric Sievers et al. showed preliminary results of the treatment of AML patients in first relapse (n=45) with an agent consisting of a humanized anti-CD33 antibody linked to calicheamicin (a potent cytotoxic chemotherapy). The intravenous administration of this agent (CMA-676, Wyeth-Ayerst Research) demonstrated an acceptable safety profile and a 38% (N=17) remission rate. (Sievers E, et al. Proc Am Soc Clin Onc 1999; 18: 7a, abstract 21) MONOCLONAL ANTIBODY (MAb) THERAPY Anti-tumor activity. X-D Yang and coworkers reported that ABX-EGF (Abgenix, Inc.), a humanized IgG2 MAb specific to the epidermal growth factor receptor (EGFr), demonstrated significant inhibition of tumor growth in human tumor xenograft models of pancreatic and renal cell carcinomas expressing EGFr. The anti-tumor activity did not require concomitant chemotherapy. (Yang X-D, et al. Proc Am Soc Clin Onc 1999; 18: 457a, abstract 1766) Anti-GVHD activity. R. Rifkin and colleagues demonstrated in a phase II trial that ABX-CBL (Abgenix, Inc.), a murine IgM MAb to CD147 (an antigen present on activated T, B, and NK cells), has activity in steroid-resistant acute GVHD (6 CRs in 23 evaluable patients). The dose limiting toxicity of this agent was severe myalgias. (Riflin R, et al. Proc Am Soc Clin Onc 1999; 18: 54a, abstract 200) Breast cancer and Herceptin®. Larry Norton et al. announced that further follow-up of a large multicenter controlled trial of HER2+ metastatic breast cancer patients (n=469) shows that patients who initially received chemotherapy plus Herceptin ( a humanized anti-HER 2 MAb) have a survival advantage compared to the group receiving chemotherapy alone (25.4 months vs. 20.9 moths, P=0.045). Herceptin was well tolerated except for cardiac dysfunction which was observed most commonly (19%) with doxorubicin regimens. (Norton L, et al. Proc Am Soc Clin Onc 1999; 18: 127a, abstract 483)
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