Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042 Journal Article
| Authors: | Koon, H. B.; Krown, S. E.; Lee, J. Y.; Honda, K.; Rapisuwon, S.; Wang, Z.; Aboulafia, D.; Reid, E. G.; Rudek, M. A.; Dezube, B. J.; Noy, A. |
| Article Title: | Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042 |
| Abstract: | Kaposi's sarcoma (KS) is a disease of multifocal vascular proliferation that requires infection with KS herpes virus (KSHV/HHV-8). Activation of the c-kit and platelet-derived growth factor (PDGF) receptors by autocrine/paracrine mechanisms follows endothelial cell KSHV infection. In a pilot study, imatinib, a c-kit/PDGF-receptor inhibitor, induced partial regression of AIDS-associated KS (AIDS-KS) in five of 10 patients. This multicenter phase II study was designed to estimate the response rate to imatinib in AIDS-KS. Secondary objectives included investigation of predictors of response and imatinib pharmacokinetics in patients on antiretrovirals. Patients received imatinib 400 mg/day by mouth for up to 12 months with dose escalation up to 600 mg/day at 3 months if their disease was stable. Thirty patients were treated at 12 AIDS Malignancy Consortium sites. Ten patients (33.3%) achieved partial response, six (20%) had stable disease, and seven (23.3%) exhibited KS progression. Nine patients completed 52 weeks of imatinib therapy. The median treatment duration was 22.5 weeks. Only five patients (16.7%) discontinued therapy owing to adverse events. Antiretroviral regimens did not significantly alter imatinib metabolism. Activating mutations in PDGF-R and c-kit were not found at baseline or at disease progression. We found no correlation with response with changes in any of the candidate cytokines. Imatinib has activity in AIDS-KS. Pharmacokinetic interactions with antiretroviral drugs did not correlate with toxicity. Thirty percent of patients showed long-term clinical benefit and remained on imatinib for the entire year. These results suggest imatinib is well tolerated and may be an alternative therapy for some patients with AIDS-KS. |
| Keywords: | adult; treatment outcome; aged; middle aged; genetics; mutation; disease course; antineoplastic agents; united states; antineoplastic agent; metabolism; imatinib; stem cell factor receptor; proto-oncogene proteins c-kit; phase 2 clinical trial; protein kinase inhibitor; enzymology; pathology; pyrimidines; time; time factors; protein kinase inhibitors; cytokine; blood; cytokines; drug antagonism; pilot study; pilot projects; disease progression; multicenter study; kaposi sarcoma; sarcoma, kaposi; piperazines; piperazine derivative; pyrimidine derivative; anti-hiv agents; platelet derived growth factor beta receptor; receptor, platelet-derived growth factor beta; molecularly targeted therapy; benzamide derivative; benzamides; molecular targeted therapy; aids-related opportunistic infections; anti human immunodeficiency virus agent; aids related complex; humans; human; male; female; article |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 32 |
| Issue: | 5 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2014-02-10 |
| Start Page: | 402 |
| End Page: | 408 |
| Language: | English |
| DOI: | 10.1200/jco.2012.48.6365 |
| PUBMED: | 24378417 |
| PROVIDER: | scopus |
| PMCID: | PMC3912327 |
| DOI/URL: | |
| Notes: | Export Date: 1 May 2014 -- Source: Scopus |
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