Increasing-dose gemcitabine plus low-dose cisplatin in metastatic non-small cell lung cancer.
Gemcitabine, a pyrimidine analog active in non-small cell lung cancer (NSCLC), is widely used with cisplatin. The potential activity of the combination has not been fully assessed: gemcitabine is not used at its maximum tolerated dose (MTD) and cisplatin shows a clearly dose-related toxicity. This trial was designed to assess the MTD and dose-limiting toxicity (DLT) of low-dose cisplatin and increasing gemcitabine dose.


METHODS
cisplatin 50 mg/m2 on day 1, gemcitabine starting at 1400 mg/m on days 1 and 8 every 21 days. Subsequent levels were increased by 200 mg/m2. Forty-two patients with metastatic NSCLC were enrolled (37 males; median age 61 years; squamous cell carcinoma 19 patients; performance status 2, in 13 patients; 18 patients had significant weight loss). MTD was found to be 2600 mg/m2 because of DLT in three of six patients: two neutropenic fever and one massive bleeding. Overall toxicity was generally mild consisting mainly of neutropenia. Asthenia was the most common non-hematological effect. Overall response rate was 19 out of 41 patients (46.3%) and median survival was 31 weeks. We conclude that the recommended dose for a phase II dose is gemcitabine 2400 mg/m2 days 1 and 8 as a 30-min infusion when given with cisplatin 50 mg/m2.
Artal-Cortés
Angel
A
Department of Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza, Spain. aartal@hmservet.insalud.es
Martínez-Trufero
Javier
J
Herrero
Ana
A
Puértolas
Teresa
T
Alonso
Vicente
V
Corral
Mónica
M
Ceballos
Concepción
C
Maurel
Joan
J
Antón
Antonio
A
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D000093542:Gemcitabine
D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine