Phase II study of axitinib with doublet chemotherapy in patients with advanced squamous non-small-cell lung cancer.
BACKGROUND
Axitinib is an orally active and potent tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. This phase II study assessed the efficacy and safety of axitinib combined with cisplatin/gemcitabine in chemotherapy-naïve patients with advanced/metastatic (stage IIIB/IV) squamous non-small-cell lung cancer (NSCLC).


METHODS
Axitinib (starting dose 5 mg twice daily [bid]; titrated up or down to 2-10 mg bid) was administered orally on a continuous schedule with cisplatin (80 mg/m(2) intravenously [i.v.] every 3 weeks) and gemcitabine (1,250 mg/m(2) i.v. on days 1 and 8 of each 3-week cycle), and was continued as monotherapy after completion of six cycles (maximum) of chemotherapy. The primary study endpoint was objective response rate, as defined by Response Evaluation Criteria in Solid Tumours.


RESULTS
Of the 38 patients treated, one (2.6%) patient achieved a complete response and 14 (36.8%) patients had a partial response; nine (23.7%) patients showed stable disease and three (7.9%) patients had disease progression. Median progression-free survival was 6.2 months, and median overall survival was 14.2 months. The estimated probability of survival at 12 months and 24 months was 63.2% and 30.8%, respectively. The most frequent grade ≥3 toxicities were neutropaenia and hypertension (13.2% each). Three (7.9%) patients experienced haemoptysis, of which one case (2.6%) was fatal.


CONCLUSIONS
Treatment with the combination of axitinib and cisplatin/gemcitabine demonstrated anti-tumour activity in patients with advanced/metastatic squamous NSCLC and the fatal haemoptysis rate was low. However, without a reference arm (cisplatin/gemcitabine alone), it is not conclusive whether the combination is better than chemotherapy alone. This study was registered at ClinicalTrials.gov, registration # NCT00735904, on August 13, 2008.
Oncology Department, Dnepropetrovsk Medical Academy, City Multiple-Discipline Clinical Hospital, No. 4 31 Blizhnaya Street, Dnepropetrovsk, 49102, Ukraine. oncology@dsma.dp.ua.
Igor M
IM
Bondarenko
Pfizer, Milan, Italy. antonella.ingrosso@pfizer.com.
Antonella
A
Ingrosso
Pfizer Inc, San Diego, CA, USA. paul.bycott@pfizer.com.
Paul
P
Bycott
Pfizer Inc, San Diego, CA, USA. skim@mirnarx.com.
Sinil
S
Kim
Prof. Dr. Ion Chiricută' Institute of Oncology, Cluj-Napoca, Romania. cristinacebotaru@yahoo.com.
Cristina L
CL
Cebotaru
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000077784:Axitinib; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D007191:Indazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D000093542:Gemcitabine
D007093:Imidazoles; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D003841:Deoxycytidine; D000077784:Axitinib; D002945:Cisplatin; D000093542:Gemcitabine