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

Abstract

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.

Clinical outcomes in stage III non-small cell lung cancer patients treated with durvalumab after sequential or concurrent platinum-based chemoradiotherapy – single institute experience

“…The results of PFS and OS in our series of patients with stage III NSCLC treated with durvalumab after ChT-RT confirmed improved survival compared to our historical data of treatment before durvalumab introduction. [10][11][12] After the median follow-up time of 23 months, 12-and 24-month PFS (71% and 45.8%, respectively) and OS (86.7% and 68.6%, respectively) in our series were comparable with those in the PACIFIC trial (PFS 55.3% and 44.8% and OS 83.1% and 66.3%). [1][2][3][4] In addition, data from other real-world reports have confirmed the advantage of maintenance treatment with durvalumab over ChT-RT only.…”

Phase III Non-inferiority Study Evaluating Efficacy and Safety of Low Dose Gemcitabine Compared to Standard Dose Gemcitabine With Platinum in Advanced Squamous Lung Cancer

“…Multiple small underpowered studies prior to ours have tried to address this question and a recent meta analysis of these studies suggested that low dose gemcitabine with prolonged infusion leads to a similar 1 year OS and has a lower rate of leukopenia and thrombocytopenia [12], [13], [14], [20], [21], [22], [23]. However, the authors had cautioned that the evidence was of low quality and a high quality large trial was required to answer this question and to test the validity of their results.…”

Meta-analysis of gemcitabine in brief versus prolonged low-dose infusion for advanced non-small cell lung cancer

“…A total of 1137 articles were identified by the initial search strategy. After examining the titles and full-text, six identified RCTs [ 7 – 9 , 13 – 15 ] were selected for the meta-analysis ( Fig 1 ). Nine trials were excluded because they were not randomized [ 6 , 10 , 16 – 21 ] or because the data was unavailable[ 22 ].…”

“…Another type of infusion is P-LDI, and several clinical trials [ 7 – 9 ] were established to evaluate the efficacy and safety of GEM at 30 min-SDI compared with P-LDI in patients with advanced NSCLC. In a phase I–II trial, GEM with a 6 h infusion in combination with cisplatin was used to the treat advanced NSCLC [ 10 ].…”

“…Another dose schedule is prolonged infusion of GEM at a fixed dose rate of 10 mg/m 2 /minute, and both of these dose schedules have been demonstrated to be effective and tolerable. However, several phase I and phase II clinical trials [ 7 – 10 ] have shown that GEM with P-LDI has significant antitumor activity and fewer side effects for patients with advanced NSCLC.…”