Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer: a randomized phase II clinical trial.

Background: The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid.

Patients And Methods: Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m(2) in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m(2) in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m(2) on day 2 was administered. All patients continued treatment with radiation therapy with 60-66 Gy concurrent with cisplatin 50 mg/m(2) on days 1, 8, 29 and 36 and etoposid 50 mg/m(2) on days 1-5 and 29-33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).

Results: From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively.

Conclusions: Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance.