Phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with inoperable non-small-cell lung cancer.
OBJECTIVE
To report the evidence of a phase I trial planned to determine the maximum-tolerated dose (MTD) and related toxicity of weekly gemcitabine (GEM) and concurrent radiotherapy in patients with non--small-cell lung cancer (NSCLC). In addition, the response to treatment was evaluated and reported.


METHODS
Thirty-six patients with histologically confirmed NSCLC deemed unresectable because of advanced stage were observed and treated according to a combined chemoradiation protocol with GEM as chemotherapeutic agent. GEM was given weekly for 5 consecutive weeks as a 30-minute intravenous infusion concurrent with radiotherapy (1.8 Gy/d; total dose, 50.4 Gy). The initial dose was 100 mg/m(2). Pulmonary, esophageal, cardiac, hematologic, and skin toxicities were assessed. The dose of GEM was increased by 50 mg/m(2) up to a dose of 250 mg/m(2); an additional increase by 25 mg/m(2) up to the MTD was planned and realized. Three patients were enrolled for each dose level.


RESULTS
Dose-limiting toxicity was identified for the 375-mg/m(2) level with two episodes of grade 2 esophagitis and two of grade 3 pulmonary actinic interstitial disease. The weekly dose of GEM 350 mg/m(2) was well tolerated.


CONCLUSIONS
A weekly GEM dose of 350 mg/m(2) concurrent with radiotherapy was well tolerated. Promising results regarding response to treatment were observed and reported.
Trodella
Lucio
L
Department of Radiation Oncology, Università Cattolica del Sacro Cuore, Rome, Italy. ltrodella@rm.unicatt.it
Granone
Pierluigi
P
Valente
Salvatore
S
Turriziani
Adriana
A
Macis
Giuseppe
G
Corbo
Giuseppe M
GM
Margaritora
Stefano
S
Cesario
Alfredo
A
D'Angelillo
Rolando M
RM
Gualano
Gina
G
Ramella
Sara
S
Galetta
Domenico
D
Cellini
Numa
N
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine