Phase II study of a novel taxane (Cabazitaxel-XRP 6258) in previously treated advanced non-small cell lung cancer (NSCLC) patients.

PURPOSE: Given the success of cabazitaxel in patients with prostate cancer who progressed after receiving prior chemotherapy, its preclinical efficacy in various cell lines and possible ability to cross blood-brain barrier, cabazitaxel was hypothesized to increase objective response rate (ORR) in second-line setting in non-small cell lung cancer (NSCLC). METHODS: This was a phase II 2-stage trial in 28 patients using two different treatment schedules (A: 20 mg/m(2) every 3 weeks intravenously and B: 8.4 mg/m(2) intravenously weekly) to determine the ORR of cabazitaxel with secondary end points including progression-free survival (PFS), safety, and overall survival (OS). RESULTS: There was one objective response in schedule B. PFS and OS of schedule A was 3 and 6 months, respectively. PFS and OS of schedule B was 3 and 13 months, respectively. The stable disease rate was higher in schedule A (SD = 69.23 %; 95 % CL 38.57, 90.90) as compared to schedule B (SD = 38.46 %; 95 % CL 13.86, 68.42), but this difference was not statistically significant (P value = 0.1156). There were two grade 5 toxicities from sepsis. Hematuria of any grade developed in greater percentage of patients (35%) as compared to previous cabazitaxel phase 3 trial and led to change in our protocol. CONCLUSIONS: Response to cabazitaxel in NSCLC was not as robust as seen in prostate cancer and not superior to currently used agents such as docetaxel, pemetrexed, and erlotinib. In absence of significant objective responses, the second stage of the study was not undertaken.

Phase I/IIa study of sequential chemotherapy regimen of bendamustine/irinotecan followed by etoposide/carboplatin in untreated patients with extensive disease small cell lung cancer (EDSCLC).

PURPOSE: The sequence bendamustine (B) + Irinotecan (I) followed by etoposide (E) + carboplatin (C) was hypothesized to increase progression-free survival (PFS) and overall survival (OS) in untreated extensive-disease small cell lung cancer (EDSCLC) patients compared to historical controls by exploiting mitotic catastrophe. Absent expression of ERCC-1 and expression of topoisomerases were hypothesized to be predictive for PFS and OS. METHODS: This was a phase I/IIa trial in 30 patients to determine the maximum tolerated dose (MTD) of B + I and the PFS of B + I E + C with secondary end points including overall response rate (ORR) and OS. Biomarkers measured by immunohistochemistry (IHC) obtained from diagnostic specimens were correlated with outcome. RESULTS: The MTD of B + I was not reached. During treatment with B + I, there were two grade 5 toxicities from neutropenic sepsis and metabolic encephalopathy. Other toxicities included fatigue, nausea/vomiting, diarrhea, and weight loss. For the sequence, the PFS and OS were 6.0 months and 10 months, respectively. The ORR for B + I and the sequence were 82% and 83%, respectively. Topoisomerase-2 expression was predictive for TTP and OS, but absent ERCC-1 expression was not, contrary to our hypothesis. CONCLUSIONS: B + I is an active regimen in EDSCLC. Toxicities included two grade 5 events but were otherwise manageable. The novel sequence B + I E + C increased PFS and OS compared to historical controls. Correlative studies are conflicting regarding the mechanism of action of this novel sequence.