Prediction from creatinine clearance of thrombocytopenia and recommended dose in patients receiving (glycolato-O,O')-diammine platinum (II) (NSC 375101D).
Thrombocytopenia is the most serious dose-limiting toxicity of (glycolato-O,O')-diammine platinum (II) (254-S; NSC 375101D), one of the new platinum analogues. A total of 38 patients treated with 100 mg of 254-S per m2 in a clinical phase II study were retrospectively analyzed to determine the factors influencing thrombocytopenia. Performance status, sex, age and prior chemotherapy did not affect either the percent reduction of platelets or the nadir platelet count. However, creatinine clearance (Ccr.: ml/min) was found to be a predictive variable for thrombocytopenia. There was a significant relationship between nadir platelet count and Ccr. (R2 = 0.637) or relative dose [RD = (dose of 254-S: mg/m2)/Ccr.] (R2 = 0.707). From these observations, the following equations for predicting nadir platelet count associated with administration of 254-S were proposed. [Nadir platelet count] = -64,264.7 + 2,783.4 x [Ccr.] (A) log [Nadir platelet count] = -1.6743 log [RD] + 5.32 = -1.6743 log [Dose/Ccr.] + 5.32 (B) If we administer 100 mg of 254-S per m2 to a patient with Ccr. of less than 40.3 ml/min, thrombocytopenia of grade 3 or more according to the Eastern Cooperative Oncology Group (ECOG) criteria (less than 50,000/mm3) can be predicted from equation (A). In these patients, dose modification using equation (B) is recommended.
Sasaki
Y
Y
Department of Medical Oncology, National Cancer Center Hospital, Tokyo.
Fukuda
M
M
Morita
M
M
Shinkai
T
T
Eguchi
K
K
Tamura
T
T
Ohe
Y
Y
Yamada
K
K
Kojima
A
A
Nakagawa
K
K
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D003404:Creatinine / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D010976:Platelet Count; D013921:Thrombocytopenia / Q000139:chemically induced*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C053989:nedaplatin; D003404:Creatinine