{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T20:56:26Z","timestamp":1778705786897,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,6,28]],"date-time":"2002-06-28T00:00:00Z","timestamp":1025222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Interleukin\u20102 (IL\u20102) has activity in metastatic melanoma when given in high doses by the intravenous (IV) route, but its side effects and effectiveness when given in intermediate to high doses by the subcutaneous (SC) route have not been studied adequately. This study sought to determine the maximum tolerated dose (MTD) of IL\u20102 administered once daily by the SC route.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Outpatients with progressive metastatic melanoma after chemotherapy were enrolled in a Phase I trial of IL\u20102 administered SC daily for 5 days per week for 4 consecutive weeks, repeated at 6\u2010week intervals. Patients were instructed to drink at least 2 L of fluid daily. IL\u20102 pharmacokinetic studies were performed at the two highest dose levels. Toxicity was recorded weekly using the National Cancer Institute Common Toxicity Criteria. Response was assessed at 6\u2010week intervals.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Three patients, 6 patients, 6 patients, and 4 patients received a median of 2 courses of SC IL\u20102 at dose levels of 6 MIU\/m<jats:sup>2<\/jats:sup>, 9 MIU\/m<jats:sup>2<\/jats:sup>, 12 MIU\/m<jats:sup>2<\/jats:sup>, and 15 MIU\/m<jats:sup>2<\/jats:sup>, respectively. Failure to maintain adequate fluid intake was responsible for 2 episodes of syncope at the 9 MIU\/m<jats:sup>2<\/jats:sup> dose level and for 2 incidents of reversible prerenal azotemia at the 15 MIU\/m<jats:sup>2<\/jats:sup> dose level. IL\u20102 treatment was resumed in these patients without incident. At the 15 MIU\/m<jats:sup>2<\/jats:sup> dose level, 2 patients had severe headaches, depression, and visual hallucinations requiring discontinuation of treatment. Cough and fluid retention at the end of the third and fourth weeks at the 15 MIU\/m<jats:sup>2<\/jats:sup> dose level approximated the symptoms reported by inpatients treated by continuous IV infusion at 9 MIU\/m<jats:sup>2<\/jats:sup> on the same schedule. There was a partial response and a complete response in subcutaneous disease at the 12 MIU\/m<jats:sup>2<\/jats:sup> and 15 MIU\/m<jats:sup>2<\/jats:sup> dose levels, respectively, each lasting &lt; 2 months. Plasma IL\u20102 levels after SC injection of 1000\u20135000 pg\/mL reached maximum by 3 hours and were detectable for up to 48 hours after administration. The half\u2010lives for SC IL\u20102 absorbance and clearance were 1.6 hours and 5.2 hours, respectively, and the calculated area under the curve was 30,584 pg\/mL \u00d7 hour.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>SC IL\u20102 was well tolerated and had high sustained bioavailability at the higher doses studied. The MTD for a daily SC regimen was 12 MIU\/m<jats:sup>2<\/jats:sup> and is recommended for future studies. Cancer 2002;95:127\u201334. \u00a9 2002 American Cancer Society.<\/jats:p><jats:p>DOI 10.1002\/cncr.10631<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.10631","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T19:33:49Z","timestamp":1030304029000},"page":"127-134","source":"Crossref","is-referenced-by-count":44,"title":["Phase I trial of subcutaneous recombinant human interleukin\u20102 in patients with metastatic melanoma"],"prefix":"10.1002","volume":"95","author":[{"given":"Omar","family":"Eton","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael G.","family":"Rosenblum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sewa S.","family":"Legha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wehei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Jo East","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agop","family":"Bedikian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Papadopoulos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Buzaid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert S.","family":"Benjamin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,6,28]]},"reference":[{"key":"e_1_2_5_2_2","volume-title":"FDA medical reviewers report BLA supplement 97\u20100501 proleukin indication: treatment of metastatic melanoma","author":"Litwin SD","year":"1998"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1999.17.7.2105"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01518453"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01741084"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0142(19960101)77:1<89::AID-CNCR15>3.0.CO;2-4"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1998.16.9.2921"},{"key":"e_1_2_5_8_2","first-page":"168","article-title":"Efficacy of interleukin\u20102 in the treatment of metastatic melanoma. 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