In a phase III study of women with metastatic or recurrent breast cancer, combining doxorubicin with DPPE — an analog of tamoxifen significantly — prolonged survival compared with doxorubicin treatment alone. This occurred despite no improvement in disease progression.
“Doxorubicin remains one of the most active single agents for metastatic breast cancer, [but] improving its therapeutic index has proven difficult,” investigators point out. “Therefore, the results of this study are particularly provocative.” DPPE (N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine; tesmilifene) posses novel antihistaminic properties and has been shown to augment the cytotoxicity of a variety of chemotherapy agents, according to a paper in the January 15th Journal of Clinical Oncology. In a phase II study, DPPE plus doxorubicin led to greater response rates than doxorubicin alone, and was the impetus for the phase III trial, in which 305 women with metastatic disease were randomly assigned to IV doxorubicin every 21 days alone or with IV DPPE (5.3 mg/kg). The cumulative dose of doxorubicin in both groups was 450 mg/m?. Because DPPE has gastrointestinal and neurologic side effects, women receiving it were “aggressively premedicated to ameliorate toxicity.” Most were sedated for at least 6 hours on the day of treatment. In contrast to phase II results, the phase III study failed to show a statistically significant difference in response rates between DPPE/doxorubicin and doxorubicin alone, Dr. Lesley Seymour from Queens University in Kingston, Ontario, Canada and colleagues report. There was also no significant between-group difference in progression-free survival, although there was a trend toward a positive hazard ratio (0.85). Despite this, DPPE plus doxorubicin was “statistically superior” to doxorubicin alone in overall survival, with a hazard ratio of 0.66. The researchers admit they are at a loss to explain this survival advantage at present. “This novel compound clearly warrants additional clinical and laboratory evaluation to elucidate further its apparent effect on prolongation of survival in the absence of any significant effect on response or progression,” they write. These studies are planned. (Source: J Clin Oncol 2004;22:269-276: Reuters Health: February 19, 2004: Oncolink)