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

“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 16-21 years

CCGCALGB

# pts 196 103

Years 1989-95 1988-98

CR 96% 93%

EFS @ 3 yrs 64% 38%

Median Surv. NR 5.2 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

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

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

Years from Study Entry

Pro

po

rtio

n

0 2 4 6

0.0

0.2

0.4

0.6

0.8

1.0

Survival By Disease

SNCL3 ALL

N= 49N= 33

Events= 22Events= 17

Median= 4.61Median= 1.23

Chi-square=p-value

0.140.708

CALGB 9251