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40 Years of Progress
1. 40 Years of Progress
Clifford Hudis, MD, FACP, FASCO
2. Hormone Therapy Was The First
Targeted Therapy
1896 GT Beatson - Oophorectomy in premenopausal women
1944 A Haddow - Synthetic estrogen (stilbestrol) as treatment
of breast cancer
1952 C Huggins - Adrenalectomy
(1966 Wins Nobel Prize for development of
endocrine therapy in prostate cancer)
1958 E Jensen - Characterization of the estrogen receptor (ER)
4. Edgewater Hotel, Chicago, Illinois
Fred J.
Ansfield, MD
Harry F.
Bisel, MD
Robert
Talley, MD
William
Wilson, MD
Herman H.
Freckman, MD
Jane C.
Wright, MD
Arnoldus
Goudsmit, MD,
PhD
Founders
http://www.asco.org/about-asco/founders
8. 1st ASCO Meeting in Chicago
November 5, 1964
• Development of an annual meeting
• Building educational material
• Publication of a specialty journal
• Collaboration with other organizations
• Research initiatives, and
• Development of an organizational framework to support our
efforts
9. A brief history of platinums
1845 – Peyrone described cis-PtCL2(NH3) “Peyrone’s Salt”
Ann Chemie Pharm 1845, 51: 129
1893 – Werner deduced structure
1960s – Rosenberg and van Camp discover that electrolysis of a
platinum electrode produces CDDP. This inhibits E. coli.
(They grow very large but don’t divide.)
Nature 1965, 205 (4972): 698–699.
10. A brief history of platinums
1971 – Clinical trials begin
1978 – FDA approval: ovary and testes
1989 – FDA approval: for CBDCA in ovary (similarly forms
preferential cross-links with guanine in DNA, cross-
resistant w/ CDDP)
“Class” now includes alkylating-like agents:
Nedaplatin, Oxaliplatin, Triplatin tetranitrate, & Satraplatin
13. 1977
• FLASCO was formed and committed to
facilitating and promoting multidisciplinary efforts
to improve patient care in Florida.
• Chemotherapy was established as potentially
curative therapy:
o HD
o NHL
o Early Stage Breast Cancer
o Testes Cancer
14. Systemic RX: Historical Perspective
1985 NIH Consensus Conference:
Premenopausal, node (+) : Chemotherapy
Premenopausal, node (-) : treatment not recommended,
consider chemotherapy if "high risk"
Postmenopausal, node (+), ER (+) : tamoxifen
Postmenopausal, node (+), ER (-) : consider chemotherapy,
but cannot be recommended as standard practice
Postmenopausal, node (-) : no routine adjuvant therapy,
may be considered for certain "high-risk" patients
15. EBCTCG - 2000
•Almost all women on (194) randomized trials
Randomized < 1995 w/ 5+ years f/u
and survival main endpoint
•Tamoxifen:
•50,000: tamoxifen (15,000: 5 yrs vs none)
•Ovarian Ablation: 4900 + 4200 for Goserelin
•Chemotherapy:
28,000 (polychemo)
Lancet 2005; 365:1687-1717
19. http:wikipedia/imatnib Druker BJ et al. N Engl J Med
2001;344:1038-1042.
Time to Relapse in Patients with Myeloid or Lymphoid Blast Crisis
Who Had a Response to STI571.
22. Olaparib in Ovarian Cancer
Ledermann J et al. N Engl J Med 2012;366:1382-1392.
Interim survival analysis (ASCO 2013)
•HR 0.18 (95% CI 0.11-0.31) in gBRCAm
•PFS 11.2 v 4.3 mo
•No difference in OS (?xover)
23. Fan C et al. N Engl J Med 2006;355:560-569.
Relapse-free Survival and Overall Survival
among the 225 Patients with ER+ Disease
Relapse-free Survival and Overall
Survival among all 295 Patients
Intrinsic Subtype
(Panels A and B)
Recurrence Score
(Panels C and D)
70-Gene Profile
(Panels E and F)
Wound Response
(Panels G and H)
Two-Gene Ratio
(Panels I and J).
Prognostic Performance:
