title: Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft.
abstract: The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation.
authors.affiliation: Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, Melbourne, VIC, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Joschko
authors.forename: L K
authors.initials: LK
authors.lastname: Webster
authors.forename: J F
authors.initials: JF
authors.lastname: Bishop
authors.forename: J
authors.initials: J
authors.lastname: Groves
authors.forename: K
authors.initials: K
authors.lastname: Yuen
authors.forename: I N
authors.initials: IN
authors.lastname: Olver
authors.forename: K N
authors.initials: KN
authors.lastname: Narayan
authors.forename: D L
authors.initials: DL
authors.lastname: Ball
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy*; D002945:Cisplatin / Q000097:blood / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000627:therapeutic use*; D011878:Radiotherapy; D014407:Tumor Cells, Cultured
chemical_list: D011838:Radiation-Sensitizing Agents; D002945:Cisplatin