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.

Response of Rat Prostate and Lung Tumors to Ionizing Radiation Combined with the Angiogenesis Inhibitor AMCA

“…The ER of 1.4-1.7 due to AMCA treatment in the L44 tumor indicates that the efficacy of radiation therapy is indeed potentiated by exposure of the tumor to AMCA. The ER observed for the L44 tumor is comparable with those found for several cytostatics such as gemcitabine [35,38,42], cisplatin [24], the camptothecin analogue RFS-2000 [2], 5-fluorouracil [33] and two taxane analogues [31]. Interestingly, in our study with the L44 tumor with AMCA no weight loss was observed in contrast to the studies with the cytostatics mentioned.…”

Modelling of tumour repopulation after chemotherapy

“…Such an increase in cycling cells is expected to overcome the cell kill by chemotherapy, leading, therefore, to tumour repopulation. The poor tumour response to cisplatin administered alone agrees with the results obtained by Joschko et al [18] from human tumour xenografts. Tumour response after cisplatin was comparable to that seen in controls (untreated tumours).…”

Metabolic Imaging of Head and Neck Cancer Organoids

“…Mice with FaDu tumors were treated 3 times a week for 2 weeks with cetuximab (33mg/kg) [23][24], cisplatin (6mg/kg) [25], or their combination via intraperitoneal injection (6 tumors per group). Tumor volumes were measured once a day using calipers, and tumor volumes were calculated by (l*w 2 )/2, where l is the tumor length and w is the tumor width.…”