Phase I study of gemcitabine and carboplatin in advanced non-small cell lung carcinoma.
BACKGROUND
This phase I study was designed to determine the maximum tolerated dose of carboplatin with a fixed dose of gemcitabine without growth factor or hematopoietic precursor support.


METHODS
Nineteen patients with previously untreated non-small cell lung cancer (NSCLC) were treated at three dose levels. Initially, the gemcitabine dose was 1000 mg/m(2) given on days 1 and 8. Of the first five patients treated with carboplatin AUC 4, three experienced dose limiting toxicity (DLT). The study was, therefore, amended to decrease the dose of gemcitabine to 800 mg/m(2) given on days 1 and 8 in a 21-day cycle.


RESULTS
Dose limiting toxicity (neutropenia and thrombocytopenia) were seen at dose level 2A (carboplatin AUC=5). Thus, no further dose escalation was performed. Grade 3 and 4 toxicities were seen as follows: leukopenia in five of 18 (28%); neutropenia, four of 18 (22%); and thrombocytopenia, four of 18 (22%) evaluable patients. Grade 3 or 4 anemia occurred in one of 18 (6%) patients and no neutropenic fever or treatment related mortality was observed. Partial responses were seen in six patients and one patient with evaluable disease had an objective response. The overall response rate was 37% (seven of 19). Six other patients had stable disease. A total of 89 courses were administered with a median of five courses per patient (range: two to six courses). The median time to progression for all patients was 3.7 months. The median overall survival was 7.4 months with four patients still alive (median follow up 13.5 months). The survival at 6 months and 1 year is 64 and 23%, respectively.


CONCLUSIONS
The maximum tolerated dose (MTD) in this group of patients was defined as carboplatin AUC 4 when administered with gemcitabine 800 mg/m(2) on days 1 and 8 of a 21-day schedule.
Gajra
A
A
State University of New York, Upstate Medical University, 750 E Adams Street, Syracuse, NY 13210, USA.
Mehdi
S A
SA
Kirshner
J
J
Newman
N
N
Graziano
S L
SL
D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced; D015993:Life Tables; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D009422:Nervous System Diseases / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D012074:Remission Induction; D016019:Survival Analysis; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine