Weekly Vinorelbine and Docetaxel as Second-Line Chemotherapy for Pretreated Non-Small Cell Lung Cancer Patients: a Phase I-II Trial

Abstract

Docetaxel was proven to be effective as second-line therapy for patients with advanced NSCLC after failure of platinum-based front-line chemotherapy. We designed this phase I/II study to define the Maximum Tolerated Dose of weekly docetaxel combined with weekly vinorelbine, and subsequently evaluate tolerability and activity of this schedule in NSCLC patients who were progressive after treatment with either cisplatin and gemcitabine or carboplatin and paclitaxel regimens. To be eligible for the study, patients were required to have a WHO performance status < or =2, failure after at least two cycles of first platinum-based chemotherapy, and no prior treatment with docetaxel and vinorelbine. A total of 27 patients were enrolled in this phase I/II study. A weekly docetaxel dose of 25 mg/m2 was recommended in combination with fixed vinorelbine dose of 20 mg/m2, and 24 patients were treated at this dose level. Severe neutropenia (62%) and febrile neutropenia (29%) were the most frequent toxicities, with 83% of patients requiring dose modification or delay. In the phase II study, 5 (21%) patients obtained a partial response, 8 (33%) patients had stable disease, whereas 10 (42%) patients progressed. After a median follow-up of 18.7 months, median survival was 8 months, with 30% surviving at 1 year. Regardless of the use of weekly docetaxel schedule, this regimen was highly myelosuppressive, and did not seem to improve response rate and survival compared to single-agent docetaxel. No further developments of this schedule are warranted.

Efficacy and safety of combination chemotherapy with mitomycin and vinorelbine for the treatment of advanced non-small cell lung cancer

“…However, the overall survival is only 7-8 months with overall response rates reported lower than 10% and 1-year survival rate of 30% [20,22,23,25]. Several trials have been published investigating combination therapies based on docetaxel, gemcitabine or vinorelbine [26][27][28] but the median overall survival remains in the range of 6-8 months and therapyassociated toxicity seems to be relatively high in most of these studies.…”

Phase II study of S-1 and docetaxel for previously treated patients with locally advanced or metastatic non-small cell lung cancer

“…Many reports have been published investigating combination chemotherapy using two non-platinum agents for recurrent NSCLC in randomized clinical trials, with the objective of improving outcomes further. However, none of these studies have demonstrated improved survival with combination chemotherapy, whereas there have been relatively higher or intolerable toxicities [13][14][15][16]. Therefore, more active regimens for the second-line chemotherapy are much needed.…”

Phase I/II trial of a biweekly combination of S-1 plus docetaxel in patients with previously treated non-small cell lung cancer (KRSG-0601)

“…However, there have been relatively higher or intolerable toxicities observed in this context (Pectasides et al , 2001; Spiridonidis et al , 2001; Nelli et al , 2004; Takeda et al , 2009). In the present study, we evaluated the efficacy and safety of a new scheduled combination of S-1 and docetaxel, each of which have shown promising efficacy in the treatment of advanced or metastatic NSCLC.…”