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document
Temozolomide and cisplatin versus temozolomide in patients with advanced melanoma : a randomized phase II study of the Hellenic Cooperative Oncology Group . PURPOSE Temozolomide ( TMZ ) is an oral alkylating agent that produces methyl adducts at the 0.6 position of guanine . The methyl adducts are removed by the DNA repair enzyme AGAT . As demonstrated by in vitro studies , cisplatin ( CDDP ) is able to down-regulate the AGAT activity , suggesting that CDDP could enhance the antitumor activity of TMZ . We designed a randomized phase II study to evaluate and compare the activity and safety profile of the combination versus single-agent TMZ in patients with advanced melanoma . PATIENTS AND METHODS From January 2000 to April 2002 , 132 patients were enrolled on the study . Patient and tumor characteristics were well balanced between the two arms . Patients with cerebral metastases were included . Patients received TMZ 200 mg/m ( 2 ) /day orally for five consecutive days every 4 weeks or TMZ + CDDP 200 mg/m ( 2 ) daily on days 1-5 and 75 mg/m ( 2 ) of CDDP on day 1 . RESULTS Tumor responses ( complete and partial responses ) were seen in 16 patients ( 26 % ) in arm A and 19 patients ( 29 % ) in arm B . The median time to progression ( TTP ) was 3.8 months in arm A and 5.8 months in arm B . The median overall survival ( OS ) was 11.5 months in arm A and 12 months in arm B . The difference between treatment arms regarding objective response rates , TTP and OS were not statistically significant . Toxicity was comparable between the two arms for anemia , leukopenia , neutropenia , thrombocytopenia , fatigue , constipation and arthralgias/myalgias . There was significantly more grade 3 and 4 emesis in the combination arm . CONCLUSIONS No clear benefit in terms of response rates , median TTP or OS was shown with the combination of TMZ + CDDP . Additionally , the combination was associated with higher incidence of grade 3 and 4 emesis .
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Intervention_Pharmacological
Temozolomide and cisplatin
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Intervention_Pharmacological
temozolomide
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Intervention_Pharmacological
Temozolomide ( TMZ )
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Intervention_Pharmacological
cisplatin ( CDDP )
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Intervention_Pharmacological
CDDP
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Intervention_Pharmacological
TMZ .
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Intervention_Pharmacological
combination versus single-agent TMZ
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Intervention_Pharmacological
TMZ 200 mg/m ( 2 ) /day orally
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Intervention_Pharmacological
TMZ + CDDP
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Intervention_Pharmacological
CDDP
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Intervention_Pharmacological
TMZ + CDDP .
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Outcome_Physical
antitumor activity of TMZ
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Outcome_Physical
Tumor responses
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Outcome_Physical
median time to progression ( TTP )
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Outcome_Mortality
median overall survival ( OS )
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Outcome_Physical
objective response rates
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Outcome_Adverse-effects
anemia , leukopenia , neutropenia , thrombocytopenia , fatigue , constipation and arthralgias/myalgias
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Outcome_Adverse-effects
grade 3 and 4 emesis
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Outcome_Other
No clear benefit
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Outcome_Physical
response rates
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Outcome_Physical
median TTP
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Outcome_Adverse-effects
grade 3 and 4 emesis
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Participant_Condition
advanced melanoma
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Participant_Condition
advanced melanoma
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Participant_Sample-size
132
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Participant_Condition
cerebral metastases