Table 2 GM-CSF-containing regimens in patients with malignant melanoma Population Arellano and Lonial Author Lutzky et al 2003 Weber et al 2005 De Gast et al 2003 Groenewegen and de Gast 1999; Groenewe- gen et al 2002 Janik et al 2001 Ravaud et al 2001 Gajewski and Flickinger 2000 Gibbs et al 2000 Vaughan et al 2000 11 31 74 32 28 32 7 72 19 Schachter et al 1998 40 Toxicities (most common) Most common: fatigue, dizziness, somnolence, constipation SAEs in 7 patients Most common toxic- ity: ﬂu-like symptoms DLT: thrombocyto- penia Grade 3–4 lymphope- nia was observed All patients developed ﬂu-like syndrome Treatment was well tolerated Treatment was well tolerated Dose alteration due to toxicity in 20% A and 4.7% B Grade 3 or 4 toxicity occurred in 40% A and 76.5% B Treatment was well tolerated Signiﬁcant toxicity with grade 2 and 4 thrombocytopenia and renal impairment Grade 3–4 toxicities: bone marrow sup- pression, hypoten- sion, pulmonary edema, confusion, and increased serum creatinine Treatment was well tolerated Concurrent therapy Thalidomide: intra- patient dose escalation 50–400 μg PO daily Temozolamide: days 1–5 INFα-2b: days 6–17 IL-2: days 6–17 Temozolamide: days 1–5 INFα-2b: days 6–17 IL-2: days 6–17 Repeated every 22 days in stable/ responding pts DTIC: day 1 IL-2: days 6–17 INFα-2b: days 6–17 Topotecan: 1.5 mg/m2 daily x 5 days Cycle repeated every 21 days A: None B: DTIC 800 mg/m2 D 1 21-day cycles Cross-over from A to B allowed for non- response/progression Cisplatin, DTIC: D1 IL-2: D 8–14 INF-α: D 8,10,12,14 28 day cycles Temozolamide: D1–5 Cisplatin: D 1–3 IL-2: D 1–4 INF-α: D 1–5 28-day cycles Cisplatin: D 1–3 DTIC: D 1–3 Tamoxifen: daily IL-2: D 6–10, 17–21 INFα-2b: days 6–10 and 17–21 28-day cycles INF-α: days 1,3,5 Carmustine: day 8 Cisplatin: days 8–10 DTIC: days 8–10 Tamoxifen: daily 21-day cycles Abbreviations: bid, twice daily;TIW, 3 times weekly; DTIC, dacarbazine; INF-α, interferon alpha; IL-2, interleukin 2; PD, progressive disease; PO, orally; PR, partial response; pt, patient; OR, overall response; mOS, median overall survival; SQ, subcutaneously; LFT, liver function test; wks, weeks; CHT, chemotherapy; D, days; DLT, dose-limiting toxicity; SAEs, serious adverse events. 22 Biologics:Targets & Therapy 2008:2(1) Dose of GM-CSF Outcomes 125 μg/m2 SQ daily × 14 days 3 alive without recur- rent disease 125 μg/m2 SQ days 6–17 2.5 μg/kg SQ days 6–17 2.5 μg/kg SQ days 2–12 250 μg/m2 SQ QD post CHT 250 μg/m2 SQ BID × 5 D prior to CHT; or none A: 5 μg/kg BID SQ × 14 D B: 5 μg/kg BID SQ D2-19, 21-day cycles 5 μg/kg SQ D 2–7 250 μg SQ days 6–25 450 μg/m2 SQ D 4,5,15,16 or 450 μg /m2 SQ D 4,5,15,16 and 225 μg/m2 SQ D 6–10, 17–21 or 450 μg /m2 SQ D 4–10, 15–21 20 μg/m2/day SQ × 7 days following chemotherapy CR: 4 PR: 4 SD: 7 mOS: 15.9 mos CR: 4 s PR: 19 SD: 13 mOS: 252 day CR: 4 PR: 6 mOS: 8 mos CR: 0 PR: 1 Best response was SD: A: 0 B: 3 OS A: 6.3 months B: 7.3 months CR: 1 PR: 1 MR: 2 CR: 1 PR: 11 mOS: 11 mos OR: 6 CR: 2 mOS: 6.2 mos. CR: 9 PR: 11 Survival beneﬁt in responders: 22 mos. vs 8 mos.(p = 0.0001)