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OBVIOUS DIFFERENCES

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.

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OBVIOUS DIFFERENCES

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  1. 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

  2. “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)

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

  4. 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.

  5. Results in patients aged 16-21 years CCG CALGB # pts 196 103 Years 1989-95 1988-98 CR 96% 93% EFS @ 3 yrs 64% 38% Median Surv. NR 5.2 yrs

  6. POSSIBLE EXPLANATIONS Differences in: • 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

  7. 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

  8. 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.

  9. 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

  10. RECENT TRIALS IN ADULTS WITH SNCL AND L3 LEUKEMIA n Age (med) OS Comments NCI 20 25 85% 85% earlier stage French 65 26 yrs 74% 56% earlier stage German 59 35 50% all L3 CALGB 54 44 52% 21% earlier stage MDA 26 58 49% all L3

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

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

  13. CALGB 9251

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