Combination of gemcitabine and cisplatin for advanced non-small cell lung cancer: a phase II study with emphasis on scheduling.
BACKGROUND
Many regimens of gemcitabine-cisplatin chemotherapy have proven activity in patients with advanced non-small cell lung cancer (NSCLC). However, the optimal dose and schedule still have to be established.


METHODS
We conducted a phase II study with administration of cisplatin 50 mg/m(2) on days 1 and 8 and gemcitabine 800 mg/m(2) on days 2, 9 and 15. This schedule was selected to optimise the synergism between the two drugs and reduce toxicity due to high dose cisplatin.


RESULTS
Thirty-six chemo-naive patients with stage IIIA, IIIB or IV NSCLC entered the study (26 men, 10 women; median age 58 years, range 29-74). Twenty patients achieved a partial response: 7 out of 10 stage IIIA patients, 7 out of 13 stage IIIB patients and 6 out of 13 stage IV patients. On intent-to-treat basis, the overall response rate (RR) was 58% (95% confidence interval, 42-74%). Ninety percent of stage IIIA patients and 46% of stage IIIB patients received adjuvant surgery or radiotherapy. Overall median duration of response was 28 weeks (range 6-147 weeks). For stage IIIA, IIIB and IV patients, these numbers were 91, 13 and 23 weeks, respectively. One-year survival was 49% with 90%, 23% and 42% for stage IIIA, IIIB and IV patients, respectively. The main toxicity was myelosuppression. WHO grades 3 and 4 leukopenia occurred in 67% of patients, whereas 61% experienced grade 3 or 4 thrombocytopenia. Although hematological toxicity was clinically tolerable, it frequently led to omission of gemcitabine administration on day 15. The incidence of non-hematological toxicity was very low.


CONCLUSIONS
This regimen of cisplatin on days 1 and 8 and gemcitabine on days 2, 9 and 15 induced a high RR in patients with advanced NCSLC. Frequent omission of gemcitabine day 15 is a limitation of this schedule. This should be an important factor in a practical approach to decide on the most optimal schedule of the cisplatin plus gemcitabine combination.
Huisman
C
C
Department of Pulmonary Diseases, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Giaccone
G
G
van Groeningen
C J
CJ
Sutedja
G
G
Postmus
P E
PE
Smit
E F
EF
D000293:Adolescent; 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; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D000093542:Gemcitabine
D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine