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document
Use of high-dose cytarabine to enhance cisplatin cytotoxicity-effects on the response and overall survival rates of advanced head and neck cancer patients . UNLABELLED It has been reported that cytarabine , acting by at least two different mechanisms , enhances the cytotoxic effect of cisplatin in in vitro systems . The aim of this open , prospective , randomised study was to estimate the eventual benefits from the inclusion of high-dose cytarabine in the cisplatin-5-fluorouracil ( 5-FU ) regimen as first-line treatment of patients with advanced head and neck cancer . The study recruited successive patients with unresectable grade I/II head and neck cancer who were not suitable for irradiation treatment ( T any N3 or T4 N2C ) , metastatic or previously irradiated . All patients gave their informed consent . A joint ear , nose and throat ( ENT ) oncological committee performed the selection . A total of 170 patients were included in the study . Patients randomised to arm A were given 1000 mg/m ( 2 ) cytarabine on day 1 preceding for 6 h cisplatin infusion , 30 mg/m ( 2 ) /24 h cisplatin intravenous ( i.v . ) bolus days 1-4 and 1000 mg/m ( 2 ) /24 h 5-FU in a 4-h infusion on days 1-4 . Patients in arm B were given cisplatin and 5-FU in the same dosage and schedule as in arm A . Additional irradiation+/-surgery was performed if and when feasible . Patients in both arms were well balanced with regard to clinical variables . The following results were obtained : Arm A : 84 patients were included , 74 were evaluable for activity ; RESPONSE complete response ( CR ) 8 ( 11 % ) , partial response ( PR ) 40 ( 54 % ) , stable disease ( SD ) 11 ( 15 % ) , progressive disease ( PD ) 15 ( 20 % ) . The overall response rate ( RR ) based on the evaluable patients was 48/74 ( 65 % , 95 % confidence interval ( CI ) 54-75 % ) ; The RR based on an intent-to-treat analysis was 57 % , 95 % CI 47-67 % ; Median survival was 13 months ; There were 50 episodes of granulocytopenia grade IV and 15 of febrile neutropenia per 316 cycles . Arm B : 86 patients were included , 80 were evaluable for activity ; RESPONSE CR 7 ( 9 % ) , PR 29 ( 36 % ) , SD 10 ( 12.5 % ) , PD 34 ( 42.5 % ) ; The overall RR based on the evaluable patients was 36/80 ( 45 % , 95 % CI 35-56 % ) ; The RR based on an intent-to-treat analysis was 42 % , 95 % CI 32-52 % ; Median survival was 8 months ; There were 14 episodes of granulocytopenia grade IV and 7 febrile neutropenias per 324 cycles . The RR was significantly higher in arm A ( P=0.013 ) , power ( one-sided ) 80 % . The proportion of patients from the appropriate subset who achieved a clinical response making additional treatment feasible was higher in arm A ( P=0.00015 ) , as well as the proportion of patients with a performance status 2+3 achieving a response ( P < 0.0001 ) . Using the Log-rank test , patients from arm A achieved a significantly longer survival ( P=0.009 ) , with the probability of survival at 12 months of 0.58 for patients in arm A and 0.28 for patients in arm B. Grade IV granulocytopenia and thrombocytopenia were more frequent in arm A . Due to its haematological side-effects , cytarabine might not be the ideal drug to modulate the cytotoxicity of cisplatin . However , other modulators of its activity could be of interest for further studies in head and neck cancer patients .
9817
Intervention_Pharmacological
cytarabine
9818
Intervention_Pharmacological
cisplatin
9819
Intervention_Pharmacological
cytarabine
9820
Intervention_Pharmacological
cisplatin
9821
Intervention_Pharmacological
cytarabine
9822
Intervention_Pharmacological
cisplatin-5-fluorouracil ( 5-FU )
9823
Intervention_Physical
irradiation treatment
9824
Intervention_Pharmacological
1000 mg/m ( 2 ) cytarabine
9825
Intervention_Physical
cisplatin infusion
9826
Intervention_Pharmacological
cisplatin
9827
Intervention_Pharmacological
cisplatin and 5-FU
9828
Intervention_Surgical
irradiation+/-surgery
9829
Intervention_Pharmacological
cytarabine
9830
Intervention_Pharmacological
cisplatin
9831
Outcome_Adverse-effects
cytotoxicity-effects
9832
Outcome_Mortality
survival rates
9833
Outcome_Physical
complete response ( CR )
9834
Outcome_Physical
partial response ( PR )
9835
Outcome_Physical
stable disease ( SD )
9836
Outcome_Physical
progressive disease
9837
Outcome_Physical
overall response rate ( RR )
9838
Outcome_Physical
RR based on an intent-to-treat analysis
9839
Outcome_Mortality
Median survival
9840
Outcome_Physical
granulocytopenia grade IV
9841
Outcome_Physical
febrile neutropenia
9842
Outcome_Physical
CR
9843
Outcome_Physical
PR
9844
Outcome_Physical
SD
9845
Outcome_Physical
PD
9846
Outcome_Physical
overall RR
9847
Outcome_Physical
RR was significantly higher
9848
Outcome_Other
proportion of patients with a performance status 2+3 achieving a response
9849
Outcome_Mortality
survival
9850
Outcome_Mortality
survival at 12 months
9851
Outcome_Physical
Grade IV granulocytopenia and thrombocytopenia
9852
Outcome_Adverse-effects
haematological side-effects
9853
Outcome_Adverse-effects
cytotoxicity