caa a22 4500 397562764 CHVBK 20180308164820.0 cr unu---uuuuu 161202e19960103xx s 000 0 eng 10.1093/jnci/88.1.44 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.1.44 Phase II Trial of Interleukin 1α and Indomethacin in Treatment of Metastatic Melanoma [Elektronische Daten] [John E. Janik, Langdon L. Miller, Dan L. Longo, Geraldine C. Powers, Walter J. Urba, William C. Kopp, Barry L. Gause, Brendan D. Curti, Robert G. Fenton, Joost J. Oppenheim, Kevin C. Conlon, Jon T. Holmlund, Mario Sznol, William H. Sharfman, Ronald G. Steis, Stephen P. Creekmore, W. Gregory Alvord, Ann E. Beauchamp, John W. Smith] Background: The rising incidence of malignant melanoma and the lack of curative therapies for metastatic disease represent a therapeutic challenge. New agents effective in treating this disease are needed. Purpose: Because of the additive antitumor effects of interleukin 1α (IL-1α) and indomethacin in vivo, we conducted a phase II trial of this combination in patients with melanoma. We used the recommended dose determined from our phase I trial to ascertain the antitumor activity of the combination. Methods: From August 1, 1990, through July 28, 1992, 49 patients entered the study. They were stratified into two groups based on the presence of visceral (n = 14) and nonvisceral (n = 35) metastases. The patients received 7 days of both IL-1α (0.1μg/kg per day by intravenous bolus infusion) and indomethacin (50 mg orally every 8 hours). At least two cycles of therapy, repeated at 21-day intervals, were planned. Additional treatment was given to those patients who had stable or responding lesions. A chi-squared test for homogeneity of proportions was used to compare groups on several measures. All P values resulted from two-sided tests. Results: Fever, chills, and hypotension were among the most common side effects. None of the 14 patients with visceral metastases responded to the treatment. Of the 35 patients with nonvisceral metastases, three showed a partial response for 6 months each and one showed a complete response for more than 34 months; the response rate was 11% (95% confidence interval [CI] = 5%-26%). All responding patients required phenylephrine for treatment of IL-1α-induced hypotension, whereas six (19%) of 31 of the nonresponding patients with nonvisceral metastases required phenylephrine (P =.0008). The response rate in women was higher; three of 10 women (30%; 95% CI =11%-60%) responded, whereas one of 25 men (4%; 95% CI = 0%-20%) responded (P =.029). All three women were positive for human leukocyte antigen (HLA) B7 expression (P =.011). Conclusions: The combination of IL-1α and indomethacin has minimal antitumor activity in melanoma patients. All responses were confined to patients with nonvisceral metastases. IL-1α-induced hypotension, gender, and HLA B7 expression were positively associated with response. Implications: Administration of higher doses of IL-1α alone has been shown to produce hypotension in a large proportion of patients but can be given safely with phenylephrine support. Because of the association of hypotension with antitumor activity, treatment with higher IL-1α doses alone may be a strategy for attaining better response rates. [J Natl Cancer Inst 1996;88:44-9] © Oxford University Press REPORTS nationallicence Janik John E. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Miller Langdon L. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Longo Dan L. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Powers Geraldine C. Program Resources, Inc/DynCorp, NCI-FCRDC Portland, OR aut Urba Walter J. Earle Chiles Research Institute, Providence Medical Center Portland, OR aut Kopp William C. Program Resources, Inc/DynCorp, NCI-FCRDC Portland, OR aut Gause Barry L. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Curti Brendan D. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Fenton Robert G. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Oppenheim Joost J. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Conlon Kevin C. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Holmlund Jon T. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Sznol Mario Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Sharfman William H. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Steis Ronald G. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Creekmore Stephen P. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut Alvord W. Gregory Data Management Services, Inc., Program Resources, Inc/DynCorp, NCI-FCRDC MD aut Beauchamp Ann E. Frederick Memorial Hospital MD aut Smith John W. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/1(1996-01-03), 44-49 0027-8874 88:1<44 1996 88 jnci https://doi.org/10.1093/jnci/88.1.44 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.1.44 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Janik John E. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Miller Langdon L. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Longo Dan L. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Powers Geraldine C. Program Resources, Inc/DynCorp, NCI-FCRDC Portland, OR aut NATIONALLICENCE 700 1- Urba Walter J. Earle Chiles Research Institute, Providence Medical Center Portland, OR aut NATIONALLICENCE 700 1- Kopp William C. Program Resources, Inc/DynCorp, NCI-FCRDC Portland, OR aut NATIONALLICENCE 700 1- Gause Barry L. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Curti Brendan D. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Fenton Robert G. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Oppenheim Joost J. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Conlon Kevin C. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Holmlund Jon T. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Sznol Mario Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Sharfman William H. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Steis Ronald G. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Creekmore Stephen P. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 700 1- Alvord W. Gregory Data Management Services, Inc., Program Resources, Inc/DynCorp, NCI-FCRDC MD aut NATIONALLICENCE 700 1- Beauchamp Ann E. Frederick Memorial Hospital MD aut NATIONALLICENCE 700 1- Smith John W. Biological Response Modifiers Program, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC) Frederick, MD aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/1(1996-01-03), 44-49 0027-8874 88:1<44 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford