Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: A phase II study Journal Article
| Authors: | Rixe, O.; Bukowski, R. M.; Michaelson, M. D.; Wilding, G.; Hudes, G. R.; Bolte, O.; Motzer, R. J.; Bycott, P.; Liau, K. F.; Freddo, J.; Trask, P. C.; Kim, S.; Rini, B. I. |
| Article Title: | Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: A phase II study |
| Abstract: | Background: Axitinib (AG-013736) is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We aimed to assess the activity and safety of axitinib in patients with metastatic renal-cell cancer who had failed on previous cytokine-based treatment. Methods: Between Oct 3, 2003, and April 7, 2004, 52 patients were enrolled. All patients who had at least one measurable target lesion received axitinib orally (starting dose 5 mg twice daily). The primary endpoint was objective response (ie, percentage of patients with confirmed complete response or partial response by use of Response Evaluation Criteria In Solid Tumors [RECIST] criteria. Secondary endpoints were duration of response, time to progression, overall survival, safety, pharmacokinetics, and patient-reported health-related quality of life. This trial is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/NCT00076011. Findings: In an intention-to-treat analysis, two complete and 21 partial responses were noted, for an objective response rate of 44·2% (95% CI 30·5-58·7). Median response duration was 23·0 months (20·9-not estimable; range 4·2-29·8). However, 12 of 23 initial responders progressed with response duration ranging from 4·2 months to 26·5 months. Additionally, 22 patients showed stable disease for longer than 8 weeks, including 13 patients with stable disease for 24 weeks or longer. Four patients had early disease progression. Three patients had missing response data. Median time to progression was 15·7 months (8·4-23·4, range 0·03-31·5) and median overall survival was 29·9 months (20·3-not estimable; range 2·4-35·8). Treatment-related adverse events included diarrhoea, hypertension, fatigue, nausea, and hoarseness. Treatment-related hypertension occurred in 30 patients and resolved with antihypertensive treatment in all but eight patients, of whom seven patients had a history of hypertension at baseline. Interpretation: Axitinib shows clinical activity in patients with cytokine-refractory metastatic renal-cell cancer. Although 28 patients had grade 3 or grade 4 treatment-related adverse events, these adverse events were generally manageable and controlled by dose modification or supportive care, or both. Further studies are needed to confirm these findings. © 2007 Elsevier Ltd. All rights reserved. |
| Keywords: | adult; cancer survival; treatment outcome; aged; aged, 80 and over; bone neoplasms; disease-free survival; middle aged; major clinical study; overall survival; clinical trial; constipation; fatigue; cisplatin; cytotoxic agent; fluorouracil; interferon; cancer growth; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; gastrointestinal hemorrhage; hypertension; monotherapy; side effect; unspecified side effect; antineoplastic agents; liver neoplasms; alpha interferon; capecitabine; drug megadose; outcome assessment; lymphatic metastasis; anorexia; cancer palliative therapy; interleukin 2; quality of life; drug eruption; phase 2 clinical trial; bone marrow suppression; bleeding; gastrointestinal symptom; nausea; stomatitis; lung neoplasms; dehydration; myalgia; weight reduction; combination chemotherapy; bone pain; antineoplastic activity; hematuria; kidney neoplasms; nephrectomy; abdominal pain; arthralgia; coughing; hyperglycemia; nail disease; chemotherapy induced emesis; drug induced headache; survival time; liver metastasis; lung metastasis; cytokine; carcinoma, renal cell; enzyme inhibitors; heart infarction; thromboembolism; drug response; gout; muscle weakness; xerostomia; limb pain; antihypertensive agent; weakness; kidney cancer; axitinib; navelbine; drug treatment failure; dyspepsia; hand foot syndrome; administration, oral; dry skin; floxuridine; epistaxis; proteinuria; imidazoles; interleukin-2; cardiomyopathy; dysgeusia; interferon-alpha; rectum hemorrhage; hematocrit; hoarseness; disease activity; blister; indazoles; amenorrhea; heart ejection fraction; callus; perianal abscess; acute abdomen; erythrocytosis; spleen hematoma |
| Journal Title: | Lancet Oncology |
| Volume: | 8 |
| Issue: | 11 |
| ISSN: | 1470-2045 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2007-11-01 |
| Start Page: | 975 |
| End Page: | 984 |
| Language: | English |
| DOI: | 10.1016/s1470-2045(07)70285-1 |
| PUBMED: | 17959415 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 157" - "Export Date: 17 November 2011" - "CODEN: LOANB" - "Source: Scopus" |
