Abstract | INTRODUCTION: METHODS: RESULTS: Eighty-four patients were randomized. Disease progression events were experienced by 28 (70%) and 26 (59%) patients in the AZD6244 and pemetrexed groups, respectively. Median progression-free survival was not statistically significantly different between the AZD6244 and pemetrexed groups (67 versus 90 days, respectively; hazard ratio 1.08, two-sided 80% confidence interval = 0.75-1.54; p = 0.79). Two patients in the AZD6244 group had a best response to treatment of partial response. In the pemetrexed group, one patient achieved a complete response and one patient a partial response. Dermatitis acneiform, diarrhea, nausea, and vomiting were the most frequently reported adverse events with AZD6244, compared with fatigue, anemia, nausea, anorexia, and dermatitis acneiform with pemetrexed. CONCLUSIONS: Oral AZD6244 showed clinical activity as second- or third-line therapy for patients with advanced NSCLC. In an unselected NSCLC population, there is no suggestion that AZD6244 monotherapy offers any advantage over standard treatment with pemetrexed. Based on preclinical data and recent clinical observations, further development of AZD6244 in NSCLC should focus on BRAF or RAS mutation-positive patients and/or AZD6244-based combination regimens.
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Authors | John D Hainsworth, Cristina L Cebotaru, Vladimir Kanarev, Tudor E Ciuleanu, Danail Damyanov, Phillip Stella, Hristo Ganchev, Gillian Pover, Clive Morris, Valentina Tzekova |
Journal | Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
(J Thorac Oncol)
Vol. 5
Issue 10
Pg. 1630-6
(Oct 2010)
ISSN: 1556-1380 [Electronic] United States |
PMID | 20802351
(Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)
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Chemical References |
- AZD 6244
- Antimetabolites, Antineoplastic
- Benzimidazoles
- Glutamates
- Pemetrexed
- Guanine
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Topics |
- Adenocarcinoma
(drug therapy, pathology)
- Adult
- Aged
- Aged, 80 and over
- Antimetabolites, Antineoplastic
(therapeutic use)
- Benzimidazoles
(therapeutic use)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, pathology)
- Cohort Studies
- Female
- Glutamates
(therapeutic use)
- Guanine
(analogs & derivatives, therapeutic use)
- Humans
- Lung Neoplasms
(drug therapy, pathology)
- Male
- Middle Aged
- Neoplasm Staging
- Pemetrexed
- Safety
- Salvage Therapy
- Survival Rate
- Treatment Outcome
- Young Adult
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