A phase II trial of high-dose cytarabine and cisplatin in previously untreated non-small cell carcinoma of the lung. A Piedmont Oncology Association Study.
Thirty-seven chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) were treated with cytarabine (3 g/m2 intravenously [IV] during 3 hours) after IV bolus cisplatin (100 mg/m2 repeated every 3 weeks). Aside from nausea and vomiting, the principal toxicity was hematologic, with Grade IV myelosuppression in 32% and Grade III in 14%. Four patients died while on study. One complete and four partial responses were observed for an overall response rate of 14%. Responses were limited to lymph node and lung metastases and occurred in two of 17 adenocarcinomas, two of 12 squamous cell carcinomas, and one of eight large cell carcinomas. At this dose, the plasma level of cisplatin is only 3 micrograms/ml and the plasma level of cytarabine is 10 to 50 micrograms/ml, compared with the levels of 10 micrograms/ml and 1000 micrograms/ml, respectively, required for in vitro synergy. The severity of myelotoxicity observed indicates that, even at these levels, cisplatin enhances cytarabine activity. The combination may prove useful in malignancies that are sensitive to cytarabine, but is not of benefit in cytarabine-resistant malignancies such as NSCLC.
White
D R
DR
Cancer Center of Wake Forest University, Bowman Gray School of Medicine, Winston-Salem, NC 27103.
Powell
B L
BL
Craig
J B
JB
Stuart
R K
RK
Schnell
F M
FM
Goldklang
G A
GA
Atkins
J N
JN
Jackson
D V
DV
Richards
F
F
Muss
H B
HB
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects; D004341:Drug Evaluation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D012074:Remission Induction; D014839:Vomiting / Q000139:chemically induced
D003561:Cytarabine; D002945:Cisplatin