A dose-finding and pharmacokinetic study of nedaplatin in elderly patients with advanced non-small cell lung cancer.
OBJECTIVE
Nedaplatin is a second-generation platinum showing favorable activity against non-small cell lung cancer (NSCLC). Dose-limiting toxicity (DLT) is thrombocytopenia, predicted by creatinine clearance (Ccr). This study was conducted to determine the recommended dose, and evaluate the toxicities, pharmacokinetics and efficacy for elderly NSCLC patients.


METHODS
Patients > or =70 years were stratified into two groups based on renal functions: Group A, Ccr > or = 60 and Group B, 40 < or = Ccr < 60. The initial doses were 80 and 60 mg/m(2) in Groups A and B, respectively. The doses were escalated in 20-mg/m(2) increments to 100 mg/m(2) until DLT.


RESULTS
Chemotherapy-naïve 39 elderly patients (Group A/Group B: 22/17) received a total of 83 cycles. Major toxicities were hematological. In Group A, one of the 15 patients at 100 mg/m(2) experienced DLT (neutropenia) and the recommended dose was determined at 100 mg/m(2). In Group B, three of the five patients had DLTs (leukopenia, neutropenia, thrombocytopenia and febrile neutropenia) at 100 mg/m(2), and the recommended dose was determined at 80 mg/m(2). The percentage decreases of neutrophil were well correlated with total and free-Pt AUCs. Partial responses were observed in 13 (33%) of the 39 patients, and 12 of the 13 patients who responded had a squamous cell carcinoma.


CONCLUSIONS
Nedaplatin was administered simply and feasibly by stratifying renal function and exerted favorable antitumor activity for elderly patients with NSCLC, especially on squamous cell carcinoma.
Yamamoto
Noboru
N
Division of Internal Medicine, National Cancer Center Hospital, 5-1-1, Tsukiji Chuo-ku, Tokyo 104-0045, Japan. nbryamam@ncc.go.jp
Tamura
Tomohide
T
Kurata
Takayasu
T
Yamamoto
Nobuyuki
N
Sekine
Ikuo
I
Kunitoh
Hideo
H
Ohe
Yuichiro
Y
Saijo
Nagahiro
N
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D003404:Creatinine / Q000097:blood / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C053989:nedaplatin; D003404:Creatinine