Arellano and Lonial Verra et al 2003 Lissoni et al 2003 Smith et al 2003 Table 1 Recent trials using GM-CSF in patients with renal cell carcinoma Author Population Immune therapy Dose of GM-CSF Outcomes Correale et al 2005 19 Metastatic RCC 150 μg /day SQ D 1–5 IL-2 0.5 MIU BID SQ D 6–15 59 Progressive RCC IL-2: 4 MIU/m2 SQ INF-α :5MIU SQ × 12 days every 3 wks 25 Metastatic RCC IL-2: 6 MIU/day SQ 6 D/wk × 4 wks 2 cycles (21-day intervals) Maintenance: 6 days/ month until progres- sion 21 (13 with metastatic IL-2: 72,000 IU/kg RCC) TID × on D 2–6 and D16–20 ± GM-CSF Schmidinger et al 2001 55 Metastatic RCC Westermann et al 2001 Tate et al 2001 De Gast et al 2000 Ryan et al 2000 10 Stage IV RCC Pilot study 13 Metastatic RCC, Phase I 18 11 RCC 7 melanoma Phase I 20 Metastatic RCC Hotton et al 2000 16 pts with RCC and pulmonary metastases IL-2: 4.5 MU day 1–4 wks. 3 and 6 INF-γ: 100 μg TIW wks 1 and 4 IL-2: 4 MU/m2 SQ and INF-α: 5 MIU/m2 SQ multiple dosing schedules IL-6 1, 5, or 10 μg/kg/ day D 1–14 IL-2: 1, 4, or 8 MIU/m2, and INF-α: 5 MIU SQ × 12 days every 3 wks IL-2: 11 MIU SQ D1–4 weekly INF-α: 10 MIU SQ 2 days/week c-RA 1 mg/kg daily orally for 4 weeks IL-2: 1.5, 2.25, or 4.5 MIU/m2/day 96 h CIV D 1–4, 8–11, and 15–18 2.5 μg/kg SQ D 1–12 13 patients also received GM-CSF 0.3 μg /kg D 1–3 each week of Il-2 125 or 250 μg /m2/day SQ D 1–7 and D 15–21 400 μg SQ D 1–5 weeks 2 and 5 5 μg /kg SQ D 1 + 4 week 1 D 1, 3, 5 week 2 D 1, 3, 5 weeks 3–5 D 1, 3, 5 weeks 7–9 3 μg /kg/day D1–14 2.5 or 5 μg /kg/day SQ 1.25 μg /day SQ D 1–14 1.25, 2.25, or 2.5 g/kg/day SQ D 8–19 No PR or CR SD: 4/13 with RCC Grade 3 confusion in 4 pts (3 on IL-2 alone) PR: 4/19 SD: 11/19 mTTP = 9 months 2 year OS 42% 3 year OS 26% CR: 5/59 PR: 6/59 mOS: 9.5 mos. IL-2 alone PR: 3/13 SD: 8/13 IL-2 + GM PR: 3/12 SD: 6/12 CR: 1/53,. PR: 4/53 SD: 14/53 mOS: 12 mos PR 2/10 1/10 mixed response No responses CR: 3/11 SD: 5/11 PR: 1 SD: 3 1-year survival rate: 48% 14 evaluable 0/14 had 50% shrinkage of total tumor burden nor reduction in pulmo- nary metastases Toxicities (most common) Bone pain, asthenia, and fever Flu-like symptoms, transient LFT eleva- tions More asthenia occurred in the IL-2 + GM group No toxicities greater than grade 2 One grade 3 fever No other grade 3–4 toxicities DLT: thrombocytosis and hyperbilirubinemia DLT: fever with chills, hypotension, ﬂuid retention Grade 3 fever, fatigue, anorexia mucositis, and dermatitis One on-study death Grade 3–4 toxicities: lymphopenia, throm- bocytopenia, elevated PT, thrombosis, hypo- tension, hypocalcemia, hyperglycemia, pain, constipation Grade 5: neurologic Abbreviations: c-RA, cis-retinoic acid; CR, complete response; D, days; INF-α, interferon alpha; INF-γ, interferon gamma; OR, overall response; PR, partial response; pt, patient; SQ, subcutaneous; IL-2, interleukin 2; PR, partial response; mOS, median overall survival; LFT, liver function test; wks, weeks; mTTP, median time to progression; CIV, continu- ous intra-venous infusion; PT, prothrombin time. 20 Biologics:Targets & Therapy 2008:2(1)