OBVIOUS DIFFERENCES Other medical conditions in adults - effects of [subclinical] organ dysfunction on drug disposition Better tolerance in children.

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Presentation transcript:

OBVIOUS DIFFERENCES Other medical conditions in adults - effects of [subclinical] organ dysfunction on drug disposition Better tolerance in children with ability to deliver repetitive courses more easily (eg. l- aspariginase) Need for more of a focus on long term toxicities in children

“BIOLOGIC” ISSUES Cytogenetics - differing incidence of tel/AML, hyperdiploidy, t(9;22) - similar impact of t(4;11), t(8;14) and variants - unknown effect of hypodiploidy, t(1;19) in adults but probably similar (favorable - rare in adults) (unfavorable - much more common in adults)

“Nobody does it better” (attributed to James Bond) How about pediatric vs adult oncologists??

Outcome of adolescents and young adults with ALL: A comparison of Children’s Cancer Group (CCG) and Cancer and Leukemia Group B regimens [2009]. Stock, Sather, Dodge, Bloomfield, Larson, Nachman for CALGB and CCG.

Results in patients aged years CCGCALGB # pts Years CR96%93% 3 yrs64%38% Median Surv.NR5.2 yrs

POSSIBLE EXPLANATIONS Risk factors - groups were very similar except for slightly more pts (10 vs 5%) with t(9;22) or t(4;11) in the CALGB group Regimens Doses delivered Physicians and sites of treatment Differences in:

Highly Specific Agents Targeted inhibitors - STI571, antisense Antibodies - anti CD33 Cytotoxics Maybe a bit specific - 506U Plain old new drugs Supportive Care Cytokines Cardioprotectants “Broad” Biologic Activity Antiangiogenesis

In some ways this is also a discussion about how to develop therapeutic agents for uncommon (ie economically uninteresting for pharmaceutical companies) disorders. Currently, this is a major issue re the discovery and development of molecularly targeted therapies for hematologic manignancies.

PROGNOSTIC FACTORS Age (or stage??) “Leukemia” vs “lymphoma” LDH (or stage??) CNS involvement at diagnosis BUT…… many older patients with ALL and CNS disease are cured

RECENT TRIALS IN ADULTS WITH SNCL AND L3 LEUKEMIA nAge (med) OS Comments NCI % 85% earlier stage French6526 yrs 74% 56% earlier stage German % all L3 CALGB % 21% earlier stage MDA % all L3

STI 571 DOSING Should Shaquille O’Neal and Mugsy Bogues receive the same dose simply because they are both old enough to vote?

Pediatrics - “Short vs Long” Patte et al JCO 9:123, 1991

CALGB 9251