A pilot trial of gemcitabine and vinorelbine plus capecitabine in locally advanced or metastatic nonsmall cell lung cancer.
OBJECTIVE
We conducted a pilot study of gemcitabine, vinorelbine and capecitabine combination to evaluate its toxicity and efficacy in chemo-naive patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) after a short phase IB trial.


METHODS
Eligible chemo-naive patients with stage IIIB or IV NSCLC received outpatient administration of gemcitabine 900 mg/m2 and vinorelbine 25 mg/m2 intravenously on days 1 and 8, every 3 weeks, concurrently with capecitabine 1000 mg/m2 given orally twice a day on days 1 to 5 and 8 to 12 (dose level I), or days 1 to 6 and 8 to 13 (dose level II).


RESULTS
Between November 2002 and December 2003, 19 patients participated in the study at either dose level I (7 patients) or dose level II (12 patients). The maximum tolerated dose, defined as the dose at which no more than 1 of 6 patients in a cohort experienced a dose-limiting toxicity (DLT) in the first cycle, was not established. However, 1 of 7 patients at dose level I, and 2 of 12 at dose level II experienced DLTs (ie, grade 3 hepatotoxicity in 2 patients, and grade 3 febrile neutropenia in 1 patient). In addition, 2 patients experienced treatment-related pneumonitis requiring mechanical ventilator support after the second course of therapy. Objective tumor response was observed in 5 (26.3%) of 19 patients. Further patient accrual was stopped according to the study design.


CONCLUSIONS
This 3-drug combination showed disappointing antitumor activity against NSCLC with unexpected life-threatening pulmonary toxicity. No further investigation of this regimen is recommended for patients with NSCLC.
Lee
Dae Ho
DH
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea.
Han
Ji-Youn
JY
Yoon
Seong Min
SM
Lee
Jae Jin
JJ
Lee
Hong Gi
HG
Kim
Hyae Young
HY
Yoon
Sung Jin
SJ
Hong
Eun Kyung
EK
Lee
Jin Soo
JS
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011014:Pneumonia / Q000139:chemically induced; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
D003841:Deoxycytidine; D014747:Vinblastine; D000069287:Capecitabine; D000077235:Vinorelbine; D005472:Fluorouracil; D000093542:Gemcitabine