Scheduling cisplatin and radiotherapy in the treatment of squamous cell carcinomas of the head and neck: a modelling approach

Phys Med Biol. 2006 Aug 7;51(15):3625-37. doi: 10.1088/0031-9155/51/15/002. Epub 2006 Jul 12.

Abstract

The aim of the present work was to implement the kinetics of cisplatin into a previously developed tumour growth model and to simulate the combined cisplatin-radiotherapy treatment with the emphasis on time sequencing and scheduling of drug and radiation. An investigation into whether the effect of cisplatin-radiation is determined by independent cell kill or by cisplatin-produced radiosensitization was also undertaken. It was shown that cisplatin administered before radiation conferred similar tumour control to the post-radiation sequencing of the drug. The killing effect of the combined modality treatment on tumour increased with the increase in cell recruitment. Furthermore, the individual cell kill produced by the two cytotoxins led to an additive only tumour response when the treatments were given concurrently, suggesting that for a synergistic effect, cisplatin must potentiate the effect of radiation, through the radiosensitizing mechanisms addressed in the literature. It was concluded that the optimal timing of cisplatin should be close to radiation. The model showed that daily administration of cisplatin led to a 35% improvement of tumour control as compared to radiation alone, while weekly cisplatin has improved radiotherapy by only 6%.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use*
  • Combined Modality Therapy / methods*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Kinetics
  • Models, Theoretical
  • Radiotherapy Planning, Computer-Assisted / methods*
  • Time Factors

Substances

  • Antineoplastic Agents
  • Cisplatin