Variations in tumor levels of cis-platinum through a course of fractionated radiotherapy in patients with non-small cell lung cancer

Tumori. 1997 Nov-Dec;83(6):904-6. doi: 10.1177/030089169708300606.

Abstract

Aims and background: Radiation has been shown to affect the uptake of micromolecules by the tissues within the radiation fields. We measured tumor drug uptake throughout a course of radiotherapy for stage III non-operable non-small-cell lung cancer (NSCLC).

Patients and methods: Thirty patients were treated with radiotherapy consisting of 15 fractions of 300 cGy given over 3 weeks. They were divided into groups of 2. At 1.5 hr before a given fraction of radiotherapy, one group was given i.v. a bolus of 6 mg/m2 CDDP (cis-diamminedichloroplatinum). Between 1.5 and 2 hr after radiotherapy, the patients underwent bronchoscopy, during which a biopsy was taken from the tumor mass. A similar procedure was carried out on a different group of 2 patients at each of the 15 radiotherapy fractions. The amount of platinum in the biopsy sample was measured by atomic absorption spectroscopy and expressed as ng platinum/mg tissue. In another 13 patients, a biopsy was taken before beginning the radiotherapy, and they served as controls.

Results: The quantity of platinum/g of tissue in the patients was 11 +/- 4.4 ng/mg tissue. During the course of fractionated radiotherapy, the quantity of platinum/g of tumor varied considerably between radiotherapy fractions. Maximum uptake was at fractions 8 and 9 (92 ng platinum/mg tissue) with the minima during the first few fractions and at fractions 10, 11 and 12 (an average 20 ng platinum/mg tissue).

Conclusions: The cyclical variations in the uptake of CDDP by the tumor tissue during the protracted course of fractionated radiotherapy are probably due to the well-known effects of radiation on vascular function and capillary permeability. The results may have implications for future clinical protocols involving chemo- and radiotherapy for the treatment of the disease.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / radiotherapy*
  • Cisplatin / pharmacokinetics*
  • Cisplatin / therapeutic use
  • Dose Fractionation, Radiation
  • Female
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / radiotherapy*
  • Male
  • Middle Aged
  • Pilot Projects
  • Radiation-Sensitizing Agents / pharmacokinetics*
  • Radiation-Sensitizing Agents / therapeutic use
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Radiation-Sensitizing Agents
  • Cisplatin