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Biologic Comparisons in Oncology: Pediatrics Versus Adults

Explore the differences in biologic issues between pediatric and adult oncology, focusing on various medical conditions, effects of organ dysfunction, and long-term toxicities. Compare cytogenetics impact, treatment outcomes, and prognostic factors like age and stage. Discuss recent trials in adult patients with subclinical and L3 leukemia. Highlight the importance of tailored dosing in different age groups for effective treatment.

william-kennedy
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Biologic Comparisons in Oncology: Pediatrics Versus Adults

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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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