Angiogenesis inhibitor IM862 is ineffective against AIDS-Kaposi's sarcoma in a phase III trial, but demonstrates sustained, potent effect of highly active antiretroviral therapy: From the AIDS malignancy consortium and IM862 study team Journal Article
| Authors: | Noy, A.; Scadden, D. T.; Lee, J.; Dezube, B. J.; Aboulafia, D.; Tulpule, A.; Walmsley, S.; Gill, P. |
| Article Title: | Angiogenesis inhibitor IM862 is ineffective against AIDS-Kaposi's sarcoma in a phase III trial, but demonstrates sustained, potent effect of highly active antiretroviral therapy: From the AIDS malignancy consortium and IM862 study team |
| Abstract: | Purpose: IM862 is a synthetic dipeptide (L-glutamine L-tryptophan) with in vitro and in vivo antiangiogenic properties. Phase I/II studies showed minimal toxicity and a response rate of 36% in AIDS-Kaposi's sarcoma. We report a 24-week, randomized, double-blinded, placebo-controlled phase III trial with the phase II dose, 5 mg intranasally every other day. Patients and Methods: Two hundred two HIV-positive patients were enrolled, 104 on IM862 and 98 on placebo. Results: Baseline characteristics were comparable except current antiretroviral therapy: 88% versus 96% (IM862 v placebo group; P = .042). The median treatment durations were 19.5 versus 24 weeks (IM862 v placebo). No significant difference was detected in response rate (IM862, 23%; 95% CI, 15% to 32% v placebo, 21%; 95% CI, 14% to 31%; P = .46), time to response (8.5 weeks v 14 weeks; P = .024), or duration of response. However, IM862 was associated with both a shorter time to response (8.5 weeks v 14 weeks; P = .024) and shorter median time to progression (16 weeks, 95% CI, 13 to 27 weeks v 35 weeks, 95% CI, 26 to 114 weeks; P = .012). Conclusion: Despite promising phase I and phase II studies, IM862 5 mg every other day was not superior to placebo and may accelerate time to progression. Highly active antiretroviral therapy alone was associated with a substantial rate of sustained tumor response and may have contributed to prior estimates of IM862 response. Therapeutic trials for AIDS-Kaposi's sarcoma must account for ongoing immune reconstitution in the setting of concurrent highly active antiretroviral therapy that may confound estimates of therapeutic activity. © 2005 by American Society of Clinical Oncology. |
| Keywords: | vasculotropin; adult; controlled study; treatment outcome; aged; middle aged; major clinical study; clinical trial; disease course; angiogenesis inhibitor; placebo; drug withdrawal; treatment duration; comparative study; human immunodeficiency virus infection; follow up; follow-up studies; controlled clinical trial; infection; skin defect; randomized controlled trial; angiogenesis; drug mechanism; drug response; remission; remission induction; human immunodeficiency virus; acquired immune deficiency syndrome; acquired immunodeficiency syndrome; phase 3 clinical trial; antiretrovirus agent; cd4 lymphocyte count; highly active antiretroviral therapy; kaposi sarcoma; virus load; sarcoma, kaposi; double blind procedure; double-blind method; angiogenesis inhibitors; anti-hiv agents; placebos; opportunistic infection; dipeptides; viral load; administration, intranasal; aids-related opportunistic infections; anti human immunodeficiency virus agent; aids related complex; im 862; dipeptide; self administration; thymogen; drug self administration; intranasal drug administration |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 23 |
| Issue: | 5 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2005-02-10 |
| Start Page: | 990 |
| End Page: | 998 |
| Language: | English |
| DOI: | 10.1200/jco.2005.11.043 |
| PUBMED: | 15598977 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - Presented in part at the 6th International Conference on Malignancies in AIDS and Other Immune Deficiencies, April 22-24, 2002, in Bethesda, MD - "Cited By (since 1996): 25" - "Export Date: 24 October 2012" - "CODEN: JCOND" - "Source: Scopus" |
