Effectiveness in inhibition of recovery of cell survival by cisplatin and carboplatin: influence of treatment sequence

Journal Article · Sat Jun 01 04:00:00 EDT 1991 · International Journal of Radiation Oncology, Biology and Physics; (United States)

DOI:https://doi.org/10.1016/0360-3016(91)90233-T· OSTI ID:5265348

Schwachoefer, J H.C.; Crooijmans, R P; Hoogenhout, J; Kal, H B; Theeuwes, A G ^[1]

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1. Univ. Hospital Nijmegen (Netherlands)

Clinical protocols have been designed to combine platinum-based drugs and radiation in the treatment of cancer. The rationale for this approach has been developed from preclinical studies demonstrating that platinum compounds can potentiate the cytotoxic effects of radiation toward cells. In the present study multicellular spheroids derived from squamous cell carcinoma cell line HN-1 have been used to study the effects of both cisplatin and carboplatin when administered prior to, concurrently, and after irradiation treatment. To study the influence of platinum compounds on sublethal damage repair, single and split doses of radiation were applied. Growth delay and proportion cured spheroids served as endpoints. Both cisplatin and carboplatin had no potentiating effect when administered 24 hr prior to irradiation. When administered 3 hr after completion of irradiation procedures, growth delay after single and split doses were enhanced to the same extent. The drug enhancement ratio for cisplatin was larger (1.5) than for carboplatin (1.2). Both single and split doses were enhanced by the same factor, which was interpreted as no effect on sublethal damage repair. When platinum compounds were present in the target cells at the time of irradiation, especially the split dose radiation response was strongly enhanced: the drug enhancement ratio was 3.9 for cisplatin and 3.2 for carboplatin. Recovery from sublethal damage was totally repressed. This study shows that platinum compounds can potentiate radiation and that for maximum effect the sequence of the two treatment modalities is of utmost importance. Moreover, these results may in part explain the heterogeneous outcomes of trials combining platinum compounds and radiation.

• OSTI ID: 5265348
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (United States), Journal Name: International Journal of Radiation Oncology, Biology and Physics; (United States) Vol. 20:6; ISSN IOBPD; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

550600 -- Medicine
550603* -- Medicine-- External Radiation in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANTINEOPLASTIC DRUGS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARCINOMAS
COMBINED THERAPY
DISEASES
DOSES
DRUGS
ELEMENTS
FRACTIONATED IRRADIATION
IN VITRO
INHIBITION
IRRADIATION
METALS
NEOPLASMS
PLATINUM
PLATINUM METALS
RADIATION DOSES
RECOVERY
REPAIR
SUBLETHAL IRRADIATION
SURVIVAL TIME
THERAPY
TRANSITION ELEMENTS
TUMOR CELLS