Effect of treatment sequence with radiotherapy and the antiestrogen EM 800 on the growth of ZR 75 1 human mammary carcinoma in nude mice.
We demonstrated previously that continuous administration of EM-800, a SERM having pure antiestrogenic activity in the mammary gland and endometrium in combination with monthly radiotherapy caused a greater inhibition of human ZR 75 1 tumor growth in nude mice than either therapy used alone. To further optimize therapy, we have now examined the effect of various treatment sequences to determine the optimal treatment regimen in the same model. EM 800 was given at the maximally effective oral dose of 300 microg daily. External beam radiation therapy (RTX) was carried out (2 Gy/tumor/day, 5 days per week for 3 weeks) for a total of 30 Gy/tumor delivered directly to the tumor while shielding the rest of the animal body. There was no evidence of RTX-related morbidity. Continuous treatment with EM 800 was initiated either 3 weeks before or at the same time as RTX, immediately after RTX, or 3 weeks before and immediately after RTX. After 156 days of treatment, EM 800 alone caused a 75% decrease in average tumor area, an effect equivalent to that achieved by ovariectomy. RTX alone, on the other hand, caused a transient 30% decrease in tumor area regardless of treatment sequence, whereas combined treatment with EM 800 and RTX was superior to either treatment alone. Combined treatment with EM 800 and RTX both started on Day 1 caused the greatest (88%), most rapid (50% in 2 weeks) and sustained decrease in tumor size. The present data indicate that optimal reduction in breast tumor size is achieved by continuous administration of EM 800 and RTX started simultaneously on Day 1.
Gutman
Mathieu
M
Oncology and Molecular Endocrinology Research Center, CHUL and Laval University, Quebec, Canada.
Couillard
Steeve
S
Labrie
Fernand
F
Candas
Bernard
B
Labrie
Claude
C
D000818:Animals; D001578:Benzopyrans / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D011422:Propionates / Q000627:therapeutic use*; D011878:Radiotherapy / Q000295:instrumentation / Q000379:methods; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D001578:Benzopyrans; D004965:Estrogen Antagonists; D011422:Propionates; C106945:EM 800