Phase I study of twice-weekly gemcitabine and concurrent thoracic radiation for patients with locally advanced non-small-cell lung cancer.
OBJECTIVE
To determine the maximum tolerated dose (MTD) and dose-limiting toxicity of twice-weekly gemcitabine and concurrent thoracic radiation in patients with Stage IIIa/IIIb non-small-cell lung cancer (NSCLC).


METHODS
Seventeen patients with histologically confirmed Stage IIIa and IIIb NSCLC were studied. Gemcitabine was administered via a 30-min i.v. infusion twice weekly for 6 weeks concurrent with 60 Gy of thoracic radiation. Gemcitabine, starting at a twice-weekly dose of 10 mg/m2 (20 mg/m2/week), was escalated in 10-15 mg/m2 increments in successive cohorts of 3 to 6 patients until dose-limiting toxicity was observed.


RESULTS
Of the 17 patients entered, 16 were evaluable for toxicity. The dose-limiting toxicity at 50 mg/m2 given twice weekly (100 mg/m2/week) was Grade 3 pneumonitis observed in 1 patient, Grade 3 pulmonary fibrosis in a second patient, and Grade 4 esophagitis observed in two additional patients. Twice-weekly gemcitabine at a dose of 35 mg/m2 was determined to be the MTD. The overall response rate for the 16 evaluable patients was 88%. The median survival for the entire group is 16.0 months.


CONCLUSIONS
The MTD of twice-weekly gemcitabine is 35 mg/m2 (70 mg/m2/week) given with thoracic radiation. A Phase II study within the Cancer and Leukemia Group B to ascertain the potential efficacy of this treatment regimen is in development.
Blackstock
A W
AW
Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA. ablackst@wfubmc.edu
Lesser
G J
GJ
Fletcher-Steede
J
J
Case
L D
LD
Tucker
R W
RW
Russo
S M
SM
White
D R
DR
Miller
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D013909:Thorax / Q000528:radiation effects*; D000093542:Gemcitabine
D003841:Deoxycytidine; D000093542:Gemcitabine