Phase I study of interleukin-6 in children with solid tumours in relapse.
The aim of this study was to evaluate the feasibility, toxicity and efficacy of escalating doses of subcutaneous recombinant interleukin-6 (IL-6) in children with solid tumours in relapse. Recombinant IL-6 was administered subcutaneously once daily for 14 consecutive days, with a 14 day follow-up period. The starting dose for IL-6 was 1 microgram/kg/day and was escalated in subsequent patients groups until 10 micrograms/kg. Doses were escalated every 3 patients, provided that grade III or IV organ toxicity did not occur at the preceding dose level. Twelve patients were treated, three at each dose level. No grade 3-4 major organ toxicity was observed. Flu-like symptoms and fatigue were the most common side effects. All these symptoms resolved after the end of IL-6 administration. Significant increases in acute-phase proteins (CRP [C reactive protein], fibrinogen) and ESR (Erthrocyte sedimentation rate) were observed in all patients. Stimulatory effects on thrombocytopoiesis were observed at every dose level, and were maximal at 5 micrograms/kg and 10 microgram/kg. There was no tumour response observed during IL-6 administration. Pharmacokinetic profiles performed in 3 patients are consistent with previous reports in adults. IL-6 is a promising new cytokine for paediatric oncology, in particular to increase thrombocyte counts. We recommend that further studies in children proceed at a dose of 5-10 micrograms/kg/day in a once or, better, twice daily administration.
Bouffet
E
E
Service de Pédiatrie, Centre Léon Bérard, Lyon, France.
Philip
T
T
Negrier
C
C
Ffrench
M
M
Frappaz
D
D
Gentilhomme
O
O
Gianella-Borradori
A
A
Brunat-Mentigny
M
M
Blay
J Y
JY
D000209:Acute-Phase Proteins / Q000378:metabolism; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004306:Dose-Response Relationship, Immunologic; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000628:therapy*; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D011994:Recombinant Proteins