Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours.
Br J Cancer
; 107(8): 1277-85, 2012 Oct 09.
Article
in En
| MEDLINE
| ID: mdl-22990652
ABSTRACT
BACKGROUND:
This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours.METHODS:
In all, 49 patients received axitinib 5 mg twice daily (b.i.d.) with paclitaxel/carboplatin or gemcitabine/cisplatin in 3-week cycles. Following determination of the maximum tolerated dose, a squamous cell NSCLC expansion cohort was enroled and received axitinib 5 mg b.i.d. with paclitaxel/carboplatin.RESULTS:
Two patients experienced dose-limiting toxicities febrile neutropenia (n=1) in the paclitaxel/carboplatin cohort and fatigue (n=1) in the gemcitabine/cisplatin cohort. Common nonhaematologic treatment-related adverse events were hypertension (36.7%), diarrhoea (34.7%) and fatigue (28.6%). No grade ≥3 haemoptysis occurred among 12 patients with squamous cell NSCLC. The objective response rate was 37.0% for patients receiving axitinib/paclitaxel/carboplatin (n=27) and 23.8% for patients receiving axitinib/gemcitabine/cisplatin (n=21). Pharmacokinetics of axitinib and chemotherapeutic agents were similar when administered alone or in combination.CONCLUSION:
Axitinib 5 mg b.i.d. may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug-drug interactions. Both combinations demonstrated clinical efficacy and were well tolerated.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antineoplastic Combined Chemotherapy Protocols
/
Carcinoma, Non-Small-Cell Lung
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Imidazoles
/
Indazoles
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Lung Neoplasms
Type of study:
Clinical_trials
Limits:
Adult
/
Aged
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Br J Cancer
Year:
2012
Document type:
Article
Affiliation country:
Estados Unidos