Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Br J Cancer ; 117(1): 8-14, 2017 Jun 27.
Article in English | MEDLINE | ID: mdl-28510571

ABSTRACT

BACKGROUND: Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated. PATIENTS AND METHODS: Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival rate (PFS-R) at week 8 in each cohort. Pazopanib (800 mg per day per os) was administered until progressive disease (PD). Circulating tumour cells (CTCs) were enumerated using the Cellsearch assay. RESULTS: All patients were evaluable for response and toxicity. In the intention-to-treat analysis, eight (13.8%) patients achieved partial response (PR) (95% confidence interval (CI): 5.0-22.7), 20 (34.5%) stable disease (SD) and 30 (51.7%) PD. Accrual in cohort B was halted because the hard-stop rule was met; in cohort A, the PFS-R was 59% (95% CI: 43.5-74.4; PR=7, SD=16). Nine (23.1%) patients received pazopanib for >6 months and 3 of them for >12 months. One pazopanib cycle resulted to a significant decrease to the number of patients with ⩾5 CTCs/7.5 ml of blood (20%) compared with baseline (50%). The median PFS and OS for all patients was 2.5 months (95% CI: 1.9-3.1 months) and 6.0 months (95% CI: 3.8-8.2 months), respectively (cohort A: PFS=3.7 months and OS=8.0 months). No unexpected toxicity was observed. CONCLUSIONS: Second-line treatment with pazopanib in platinum-sensitive SCLC is well tolerated and resulted in promising objective responses and disease control; CTC enumeration might serve as a reliable surrogate biomarker of response.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Neoplastic Cells, Circulating , Pyrimidines/therapeutic use , Small Cell Lung Carcinoma/drug therapy , Sulfonamides/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents , Carboplatin , Cisplatin , Disease-Free Survival , Drug Resistance, Neoplasm , Female , Humans , Indazoles , Male , Middle Aged , Treatment Outcome
2.
Br J Cancer ; 115(7): 784-8, 2016 09 27.
Article in English | MEDLINE | ID: mdl-27607471

ABSTRACT

BACKGROUND: Cabazitaxel, a semisynthetic microtubule inhibitor, has shown antitumour activity in models resistant to paclitaxel and docetaxel, and it has been approved for the treatment of docetaxel-resistant prostate cancer. We investigated its activity in patients with advanced non-small-cell lung cancer (NSCLC) progressing under or after docetaxel-based regimens. METHODS: Patients with locally advanced unresectable or metastatic NSCLC, with an Eastern Cooperative Oncology Group performance status of 0-2, were enrolled; patients had to have received up to two prior chemotherapy regimens for the treatment of advanced disease, including one docetaxel-containing regimen. Treatment consisted of cabazitaxel (25 mg m(-2) intravenously, every 21 days) until disease progression. The primary end point was the overall response rate. RESULTS: Among the 46 evaluable patients, 28.3% had squamous cell carcinoma and 54.3% had adenocarcinoma. Eight (17.4%) patients had received one and 38 (82.6%) two prior chemotherapy regimens. Treatment compliance was 95%; 26 (16%) cycles were delayed because of toxicity, (n=13) and dose reduction was required in 6 (13%) patients because of haematologic toxicity. Six (13%) patients achieved a partial response and 17 (37.0%) stable disease. The median progression-free survival and overall survival were 2.1 (95% confidence interval (CI): 1.0-3.2) and 7.4 (95% CI: 5.2-9.6) months, respectively. Grade 4 adverse events included neutropenia (n=8; 17%), febrile neutropenia (n=6; 13%) and thrombocytopenia (n=3; 6.5%). There was one treatment-related death. CONCLUSIONS: Cabazitaxel exhibits activity in NSCLC patients pre-treated with docetaxel-based chemotherapy with a substantial but manageable toxicity profile. The drug merits further evaluation in this indication.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Taxoids/therapeutic use , Adenocarcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Large Cell/drug therapy , Carcinoma, Squamous Cell/drug therapy , Disease-Free Survival , Docetaxel , Drug Resistance, Neoplasm , Drug Substitution , Dyspnea/chemically induced , Fatigue/chemically induced , Female , Gastrointestinal Diseases/chemically induced , Greece , Hematologic Diseases/chemically induced , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Taxoids/administration & dosage , Taxoids/adverse effects , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...