SELECTIVE INTRAARTERIAL INFUSION OF HIGH-DOSE CISPLATIN IN PATIENTS WITH ADVANCED HEAD AND NECK-CANCER RESULTS IN HIGH TUMOR PLATINUM CONCENTRATIONS AND CISPLATIN-DNA ADDUCT FORMATION
G. Los et al., SELECTIVE INTRAARTERIAL INFUSION OF HIGH-DOSE CISPLATIN IN PATIENTS WITH ADVANCED HEAD AND NECK-CANCER RESULTS IN HIGH TUMOR PLATINUM CONCENTRATIONS AND CISPLATIN-DNA ADDUCT FORMATION, Cancer chemotherapy and pharmacology, 37(1-2), 1995, pp. 150-154
A group of 23 patients with advanced head and neck cancer were treated
with highly selective intra-arterial (IA) cisplatin 150 mg/m(2) deliv
ered rapidly through microcatheters. The systemic effects of cisplatin
were neutralized by concurrent administration of sodium thiosulfate.
Two-to-threefold higher tumor platinum contents were detected in tumor
biopsies after selective IA cisplatin administration compared to hist
oricol controls (treated with 100 mg/m(2) IA), Cisplatin-induced DNA m
odification in human tumor biopsies was quantitated using the antiseru
m NKI-A59. High levels of cisplatin DNA adducts were detected which co
rrelated linearly with the tumor platinum content (12 = 0.62). The add
ition of radiotherapy to this high dose intensity cisplatin treatment
resulted in a 92% complete response (CR) rate (12 of 13 patients achie
ved a CR). Since no difference in tumor platinum content was detected
between patients receiving or not receiving radiotherapy (13 and 10 pa
tients, respectively), but the response rate was substantially differe
nt (12 CR and 1 partial response with radiotherapy versus 6 partial an
d 4 non-responders without radiotherapy), these data suggest that the
high platinum levels achieved by selective IA infusion were sufficient
to produce enough interaction with radiotherapy to cause a 92% CR rat
e. Whether this interaction is additive or synergistic is as yet uncle
ar.