Temporal interactions in the Lewis lung tumour between cytotoxic drugs and acute or fractionated radiotherapy.
The suggestion was examined, that acute irradiation might be combined with some cytotoxic drugs to produce a supra-additive antitumour effect by timing the second treatment to coincide with the period of repopulation by tumour cells that survived the first treatment. The possible interaction of fractionated irradiation with drugs was also studied. Lewis lung tumours were treated in vivo with acute radiation (20 Gy) and 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU, 10 mg X kg-1), cyclophosphamide (CY, 120 mg X kg-1) or cis-dichlorodiammine platinum (cis-Pt, 10 mg X kg-1) with time intervals ranging from simultaneous to 9 days in either sequence. Tumour response was measured by regrowth delay and combination responses were evaluated relative to calculated "additivity envelopes". With CY and cis-Pt, tumour volume response was approximately additive, whether the drugs were administered simultaneously, or up to 7 days before or after radiation. However, with simultaneous administration, MeCCNU and radiation were supra-additive in terms of volume response, although only additive using a clonogenic cell survival assay. A transplantation experiment suggested that the supra-additive volume response may be due to retarded growth rate in regrowing tumours. In the fractionation studies, drugs were given either at the beginning or at the end of a regime of 5 daily 6 Gy doses. With CY and MeCCNU the drugs were more effective when given with the first radiation dose, but with cis-Pt either regime was equally effective. There was no evidence that repopulation could be exploited to improve therapeutic effect with any of the combination treatments used in this study.
Stephens
T C
TC
Adams
K
K
Peacock
J H
JH
Steel
G G
GG
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000008:administration & dosage; D003037:Cobalt Radioisotopes / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D011867:Radioisotope Teletherapy; D012673:Semustine / Q000008:administration & dosage; D013997:Time Factors
D003037:Cobalt Radioisotopes; D012673:Semustine; D003520:Cyclophosphamide; D002945:Cisplatin