Treatment of head and neck and esophageal xenografts employing Alimta and concurrent ionizing radiation.
We examined the interaction between Alimta and ionizing radiation (IR) as a potential strategy to enhance the therapeutic ratio of combined-modality cancer treatment. Mice bearing human esophageal adenocarcinoma xenografts (Seg-1) or squamous cell carcinoma xenografts (SQ-20B) were treated with Alimta and IR employing a fractionated treatment schedule. Treatment with Alimta alone slowed the growth of Seg-1 but not SQ-20B tumors compared with control tumors. In Seg-1 xenografts combined treatment with Alimta and IR produced significant tumor growth inhibition compared with Alimta alone or IR alone. In SQ-20B xenografts, treatment with Alimta did not enhance IR-mediated tumor growth inhibition suggesting that sensitivity to Alimta is necessary for an interactive cytotoxic effect with IR. The present data suggest the potential clinical efficacy of combining Alimta administration with radiotherapy for Alimta-sensitive cells and indicate that further testing needs to be conducted to optimize the dosing schedule to enhance the interaction between the therapeutic agents.
Mauceri
H J
HJ
Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA.
Seetharam
S
S
Salloum
R M
RM
Vokes
E E
EE
Weichselbaum
R R
RR
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D005260:Female; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000068437:Pemetrexed; D011839:Radiation, Ionizing; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine