|S. Swisher, MD, The University of Texas M.D. Anderson Cancer Center, Houston, Tex, presented Phase I results after injecting tumors with normal p53 genes carried by a noncommon cold adenovirus. Normal p53 genes replaced the mutated form judged responsible for the unchecked cell division in the advanced nonsmall cell lung cancer (NSCLC) patients. Encouraging results followed 6 months' treatment with GPR alone and premedication with cisplatin (CDDP).|
|Rationale for GPR||Normally, tumor suppressor genes such as p53 regulate cell
growth and division. The most commonly found mutated gene in
human cancer is p53, according to J.A. Roth, MD, a colleague
of Swisher's. Abnormal p53 genes no longer stop cell division
or hasten cell death and lead to cancer.
Replacing the abnormal p53 gene needs a carrier to enter the cancer cell. The transport mechanism in this study consists of noninfectious adenovirus. It brings normal p53 genes directly into cancer cells to replace abnormal p53 genes.
|Procedure in NSCLC||Eleven NSCLC patients received escalating doses of adenoviral p53 as monthly intratumor injections for 6 months. Ten others, pretreated 3 days prior with intravenous CDDP at 80 mg/m sq also received adenoviral p53. Standard Phase I safety monitoring ensued with monthly abdominal and chest CT scans. Immunochemistry testing of lung biopsy samples preceded and followed injection of adenoviral p53.|
|Results on 20 patients||
Anti-adenoviral antibodies developed in all patients after
6 injections. Some patients showed a transient fever but none
experienced anaphylaxis. Side effects did not worsen with
At 5.5 months follow-up, the 11 patients treated with adenoviral p53 alone showed partial response, 1/11, stable disease, 5/11, and progressive disease, 5/11. Addition of CDDP in 10 others proved more promising in 9 evaluable patients: partial response, 1/9, stable disease, 8/9, and progressive disease, 0/9. Also, combined treatment with adenoviral p53 and CDDP decreased the median time to progression of the injected lesion by 37% compared with adenoviral p53 alone.
Injected adenoviral p53 monotherapy produced a dose-related tumor response. Six patients treated with 108 or 109 plaque forming units (pfu) showed partial response, 1/6, stable disease, 4/6, and progressive disease, 1/6. Lower doses such as 106 or 107 pfu in 5 other patients led to stable disease in 1/5 and progressive disease in 4/5.
|Comments||The results of this study are encouraging but require cautious interpretation in view of the small number of patients and short observation period. The investigators plan to start a Phase II study to further evaluate the safety and efficacy of adenoviral p53 in NSCLC patients.|
For professional correspondence, please contact Dr. Swisher at: firstname.lastname@example.org
Presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) on May 17-20, 1997
CONRAD NOTES, © 1997 All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078 / June 1997