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


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.
Minatel
E
E
Centro di Riferimento Oncologico, Divisione di Oncologia Radioterapica, Aviano, Italy.
Trovo
M G
MG
Ward
R
R
Gobitti
C
C
Mazza
F
F
Franchin
G
G
Bujor
L
L
Zanelli
G D
GD
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000532:radiotherapy*; D002945:Cisplatin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin