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`PROPERTY OF THE
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`
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`APOTEX V. OSI
`IPR2016-01284
`
`

`

`Thirty-Fifth
`Annual Meeting of the
`American Society of Clinical Oncology
`May15-18, 1999
`Atlanta, Georgia
`Program/Proceedings
`
`
`
`2
`2
`
`Copyright 1999 American Society of Clinical Oncology
`This material was copied
`atthe NLMband may be
`Daoist ECroraeriobe b seene
`
`

`

`Editor: Michael C. Perry, MD
`Associate Editor: Clay Anderson, MD
`
`ASCOScience and Education Program:
`Director: Michele K. Dinkel
`Assistant Director: Laura K. Ulepic
`Coordinator: Nicole Johnson
`ASCO Publications:
`Managing Editor and Director: Deborah Whippen
`Editorial Assistant: Nathan Grace
`
`The American Society of Clinical Oncology Program /Proceedings (ISBN 0-9664495-4-1) is
`published by the American Society of Clinical Oncology, Alexandria, VA 22314. The 1999 issue
`is produced and printed by Lippincott Williams & Wilkins, 351 West Camden Street,
`Baltimore, MD 21201-2436.
`
`Editorial correspondence and production questions should be addressed to American
`Society of Clinical Oncology Program/Proceedings, American Society of Clinical Oncology
`Publications Department, 850 Boylston Street, Chestnut Hill, MA 02467. Telephone:
`(617)739-8909. Fax: (617)739-8541. Email: ascopubs@asco.org.
`
`Single issue rate, $50.00. For all areas outside the United States and possessions,thereis
`an additional charge for surface delivery of $10.00. For airmail delivery, add $15.00.
`
`Prices are subject to change. Back volumesexist and are available at previous published
`prices. For further information,call (617)739-8909.
`
`Copyright © 1999, American Society of Clinical Oncology. All rights reserved. No part of this
`publication may be reproducedor transmitted in any form or by any means,electronic or
`mechanical, including photocopy, recording, or any information storage andretrieval system,
`without written permission by the Society.
`
`The American Society of Clinical Oncology assumesno responsibility for errors or omissions
`in this document. The reader is advised to check the appropriate medicalliterature and the
`product information currently provided by the manufacturer of each drug to be administered
`to verify the dosage, the method and duration of administration, or contraindications. It is
`the responsibility of the treating physician or other health care professional, relying on
`independentexperience and knowledgeof the patient, to determine drug, disease, and the
`best treatmentfor the patent.
`
`Abstract management and indexing provided by Marathon Multimedia Inc, Northfield,
`MN. Electronic page composition and print production provided by Lippincott Williams &
`Wilkins, Baltimore, MD, and the Mack Printing Group, Easton, MD.
`
`Copyright 1999 American Society of Clinical Oncology.
`3
`3
`This material was copied
`atthe NLM and maybe
`Subject US Copyright Laws
`
`

`

`Contents
`
`iv
`v
`vi
`vii
`
`Program and Proceedings Information
`ASCO OnLine (www.asco.org) Information ......0.0.0 00006 ce eee eee nee een eens
`ASCO Officers and Directors... 1... tee eee ee eee een nes
`Committee Rosters 2.0... ee ee eee eee eet ene ene beens
`Calendar of Events 2... 0.ce eee eee eee een nee een nes
`Highlight Sessions
`xv
`Opening Ceremony... 1... ee ee ee eee eee ne ee eens
`xvi
`Plenary Session . 0...ee eee eee ene eee ees
`Integrated Symposia...ee eee ee ee eee xvii
`Special Sessions 2...ee ee ee ee eee eee
`xix
`Annual Business Meeting... 0... 2.0... cc eee eee eee nee been eae
`XXlil
`Award Recipients 2.00.ee ee eee eee eee nee XXIV
`1999 ASCO Merit Awards .. 2...ee eee eee ee enn nee nes
`XXV
`GeneralInformation. .. 0.0... 0... ee tee ee ee eee ene een bbe bees
`XXV1
`ASCO Shuttle Service 2.0...ee eee ee nee eee XXIX
`Georgia World Congress Center Map .. 0.0.0.2...0. XXX1
`1999 ASCO Exhibitor List 2... eee ee eee eee en nee ene ne XxXxill
`1999 Annual Meeting Support ......ee eee ees XXXV
`Program/Proceedings . 2... 6.en ee eee tee ene es XXxvi
`ASCO ProceedingS «0...ee nn eee eee eee en ees
`la
`Plenary Session.©...ee eee eee eee la
`Adult Leukemia and Lymphoma ........ 0.00.0 eee eee eee ee eens
`2a
`Bone Marrow Transplantation/Cytokines ... 10... 0... eee ee eee eee eee ees 42a
`Breast Cancer...ee eee ee ee eee es
`66a
`Central Nervous System. 2... een ee ee eens 139a
`Clinical Pharmacology... 66 ce eee ee ee ee 155a
`Gastrointestinal Cancer... 0...ee eee ee eee eee ee eee nee 233a
`Genitourinary Cancer . 0.0. eee eee ee te ee 308a
`Gynecological Cancer... 06 ene eee ee eee 356a
`Head and Neck Cancer...0c eee eee ee ee ens
`387a
`Health Services... 0. ceen eee eee ee en eee nee ee eee
`410a
`Immunobiology and Biologic Therapy... 6.66 eee eee eas 430a
`Lung Cancer... en ee eee ee eee ees 458a
`Melanoma and Sarcoma... eee ee ee eee eens 529a
`Pediatric Oncology. 0.066ee eee tee eee 554a
`Symptom Management 0... 6.6 eee eee eens 573a
`Tumor Biology/Human Genetics. 0.0... tees 609a
`Indexes
`Disclosure Index... ee eee ee eee ee eee ene 645a
`Author Index . 0. ccc nen e eee ee eee ete eee enna 669a
`Subject Index...Ee eee 715a
`
`4
`
`

`

`
`Foes = =
`
`-
`~ ——.
`aiesseen
` Se Th temSe oesesemer
`
`HEAD AND NECK CANCER
`
`Proc
`
`eedings of ASCO Volume 18 1999
`
`
`
`388a
`
`*1498
`
`the Epidermal Growth Factor
`Dose and Schedule-Duration Escalation of
`Receptor (EGFR) Tyrosine Kinase (TK) Inhibitor CP-358, 774: A Phase | and
`
`Pharmacokinetic (PK) Study. L.£. Siu, M. Hidalgo, J. Nemunaitis, J. Rizzo,
`J. Mocezygemba, S.G. Eckhardt, A. Toicher, L. Smith, L. Hammond, A.
`Blackburn, T. Tensfeldt, S. Silberman, D.D. Von Hoff, E.K. Rowinsky. Pfizer
`Inc., Groton, CT.
`CP-358, 774 is an oral quinazolin compound which disrupts cellular signal
`transduction and triggers apoptosis via direct inhibition of EGFR TK. At
`nanomolar concentrations, CP-358, 774 inhibits purified EGFR TK and
`reduces EGFR autophosphorylation in intact tumorcells, with a selectivity
`of >1000-fold over other human TKs. Based on continuous oral dosing
`studies using xenograft models,
`the projected target average plasma
`concentration (Cavg) for clinical efficacy is 500 ng/ml. This phase | study
`was designed to assess the feasibility of administering CP-358, 774 on
`prolonged oral dosing schedules and to determine if biologically relevant
`concentrations are sustainable. Pts on Leg 1 receive CP-358, 774 on 3
`consecutive d per wk for 3 wksfollowed by 1 wk of rest. Pts on Leg 2 receive
`CP-358, 774 on d 1,
`then after a 2-d washout period, drug is given
`continuously for 3 wks followed by 1 wk ofrest. To date, 27 pts with solid
`cancers (M/F 12:15, median age 56, median KPS 90%) have completed
`61 courses on these schedules: 9 pts/23 courses on 3 doselevels in Leg 1
`(25 mg/d, 50 mg/d and 100 mg/d), 18 pts/38 courses on 5 doselevels in
`Leg 2 (50 mg/d, 100 mg/d, 150 mg/d, 200 mg/d and 100 mg bid).
`Dose-limiting gr 4 diarrhea was encountered at the 200 mg/d level in Leg 2,
`and subsequentcohort expansion to 6 pts resulted in 2 pts with gr 4 and 4
`pts with gr 1-2 diarrhea. An intermediate dose level of 150 mg/d was added
`with implementation of intensive loperamide therapy upon thefirst sign of
`diarrhea, and 2/3 pts had only gr 1 diarrhea. Accrual is ongoing at 200
`mg/d or 100 mg bid with loperamide support for diarrhea. Gr 1-2 acneiform
`rasheslimited to the upper body have been observedin 9 pts thusfar in Leg
`2, with histopathology of skin biopsies showing subepidermal neutrophilic
`infiltration and epidermal hyperproliferation. Other toxicities have been
`mild and include headache, nausea, fatigue, and transient rises in serum
`bilirubin and transaminases. Preliminary PK analysis reveals an approxi-
`mate 2-fold range in inter-subject variability in exposure. Dose-related
`increases in exposure were observed; mean Cavg values following continu-
`ous daily dosing at the 50, 100 and 200 mg/d levels in Leg 2 were 432
`(n=3), 973 (n=3) and 2120 (n=5) ng/ml,
`respectively. Dose-related
`accumulation in exposure was observed (AUCo.2, ratio d 24/d 1=1.2-4.8).
`The target Cavg of 500 ng/ml was achievable at doses=100 mg/d on a
`well-tolerated schedule.
`
`*4499
`
`;
`
`.
`
`i
`Growth Factor Receptor (EGFR)
`ion
`Study
`of Epidermal
`ft
`0
`TyrosineMoseaK)Inhibitor£P-258.774inPatentth AavancedSolid
`p,
`S.L. Silberman,
`,
`Fe
`1
`3
`_M.
`Meare BSBibIo,H Koon, Beenestne,catnch
`CT.
`Dea
`Medi
`‘on
`Israel Deaconess Medical Center,
`oston,
`:
`ton,
`(
`CP-358,774 is a novel oral anti-tumor agent that directlyinhibitsEGFR
`TK,
`sceptor that is over-expressed in many solid um S re inical
`MK arecephat CP-358,774 inhibits EGFR ale e ation and
`cell proliferation in human cell
`lines and mouse nent itmodels,The
`objectivesof this trial were to define the MTD, toxic yanthe macokinet-
`ics (PK) of weekly administration Oreo a + atingdoses were
`administered orally once every week oSyrs, OMe. tocohortsof3ts
`_
`Eighteen
`pts (median agi
`5
`Perooecincestatus 80%) with advanced solid tumors (7 june. 3prostate, 3
`lon,
`3 head
`and neck,
`1 breast, 1 renal, 1 liposarcoma
`ceive
`coeedian
`of2 (r
`t regimens were treated at 5 doses
`i
`-
`i
`atmen
`t
`a0,220, sano OESme) for a maximum period of a weeks. No
`significanttoxicities were observed at 100 and 200 mg,Toxicitiesobserved
`in subsequent cohorts included fatigue, whichwasvir 3 ys
`,
`‘
`mild, Grade (Gr) 2 headache, Gr
`1 mucositis, or
`me culopau ar
`(acneiform) rash, Gr 2 nausea, and Gr 2 diarrhea. 00 ) mg
`developed Gr 3 diarrhea, thus 3 additiona! pts receive h D0. and 13
`developed Gr2 diarrhea. Pts continue to be accrued at t ‘i
`; me dose.
`Preliminary PK analysis reveals large intra- and inter- su re varia ility,
`although relatively dose proportional increases are seen W en oses are
`escalated from 100 to 1000 mg weekly. AUCo-24 ranged
`trom 21.3
`;
`0.9 pg/ml to 4.8 ug/ml; and Cmax
`ug.hr/ml to 116.0pg.hr/ml; Cavg from
`r
`it values measured at Day 1). The ratio of Day
`from 1.5yg/ml to 7.1 pe/m! (a
`Seae Op-358,774 is a well
`8 to Day
`1 AUCp-24
`ranged from 0.66 to 1.
`tolerated oral agent when administered weekly in dosesup to 1,000me.
`The MTD has not been reached, and further dose escalation is continuing.
`
`*1500
`201839, an Oral Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase
`Inhibitor: First Phase 1, Pharmacokinetic (PK) Results in Patients. Lisa
`Hammond, M. Ranson, D. Ferry, M. Kris, H. Kelly, J. Ochs, S. Averbuch, E.
`Rowinsky. Zeneca Pharmaceuticals, Wilmington, DE.
`ZD1839 is a potent and selective inhibitor of the EGFR-associated tyrosine
`kinase involved in signal transduction and mitogenic stimulation. The IC50
`for ZD1839 enzymeinhibition of EGFR isolated from A431 vulval squa-
`mous carcinoma was 10.3-35.Ong/ml. In preclinical studies that served as
`the impetus for this study, prolonged daily oral dosing resulted in tumor
`growth inhibition and regression. This present study was designed to assess
`the feasibility of administering oral ZD1839 daily for 14 consecutive days
`to cancer patients with tumors that are known to commonly overexpress
`EGER. At thefirst dose level (for PK data purposes only), patients received
`one dose of ZD1839 followed by a seven-day washoutprior to consecutive
`ZD1839 daily dosing. To date, 27 patients (median age 51.5 years, range
`28-68 years, median KPS 1) have received 38 coursesat the following dose
`levels: 50, 100 150 and 225me/day. Drug-related toxicities (all Grade 1)
`have included anemia, leukopenia, uveitis (n=1 patient), nausea, emesis,
`HA, dry mouth and skin (n=1 patient). PK parameters (mean) for single
`and multiple dosing iterations are:
`AUC
`Tie
`Trax
`Dose
`Crax
` Level (mg) N (ng/ml) (hr) (hr) (ng*h/ml)
`
`
`
`
`
`50 single D1
`8
`45
`3.5
`34
`1301
`50 multiple D14
`6
`113
`3.7
`39
`4519
`100 single D1
`7
`46
`4.7
`-
`-
`100 multiple D14
`7
`190
`4.1
`53
`12784
`150 single D1
`7
`128
`3.6
`-
`_
`
`4 273 3.5 _150 multiple D14 -
`
`
`
`
`These results indicate that potentially biological relevant concentrations of
`7D1839 are achievable and feasible and that oral daily ZD1839 is
`well-tolerated at doses up to 225me/dayfor 14 days.
`
`*1501
`Phase I Trial of Chimerized Anti-Epidermal Growth Factor Receptor (Anti-EGFr)
`Antibody in Combination with Either Once-Daily or Twice-Daily Itradiation for
`Locally Advanced Head and Neck Malignancies. Mark P. Ezekiel, James A.
`Bonner, Francisco Robert, Ruby F. Meredith, Sharon A. Spencer, Albert F.
`LoBuglio, Harlan W. Waksal. ImClone Systems Incorporated, Somerville,
`NJ.
`Preclinical studies have revealed that combined treatment of anti-EGFr
`(C225) and irradiation results in radiosensitization in squamous cell
`carcinomas that overexpress epidermal growth factor receptor (Saleh et al,
`Proceedings Am Assoc Can Res, 37:612, 1996). Therefore, a phase| trial
`has undertaken to determine the tolerability of combined C225 and
`irradiation for patients with locally advanced (unresectable) head and neck
`malignancies. A standard dose escalation procedure was utilized with 3
`patients entered at each increment of C225 given with 70 Gy (2.0 Gy given
`once-daily: 2 Gy q d) of radiation therapy with the final 3 patients receiving
`76.8 Gy (given twice-daily: 1.2 Gy BID) with no'increment in C225 dose.
`C225 was delivered as a loading dose of 100-500 mg/m?I.V. followed by
`weekly infusions of 100-250 mg/m? x 7. Sixteen patients were entered on
`the trial with the following primary sites: oropharynx (7), oral cavity (5),
`larynx (1), hypopharynx (3). Thirteen patients had stage 1V disease and 3
`had stage II disease. One patient was not evaluable for toxicity or response
`due to recent completion of
`treatment and another patient was not
`evaluable for response due to an anaphylactic reaction (grade 4) during the
`initia! C225 treatment. The latter patient subsequently discontinued
`protocol
`therapy. Nine (56%) patients experienced irradiation-related
`grade =3 mucositis (one was grade 4) andfive (31%) patients experienced
`C225 and/orirradiation related grade 3 skin toxicity (primarily related to a
`follicular rash). No C225 dose delays were required and in general, the skin
`toxicities recovered completely or to grade 1 or 2 during treatmentor shortly
`thereafter. The irradiation-related toxicities were not exacerbated by adding
`C225 to radiation therapy. There was no increase in frequency or severity,
`nor wasthere any need for unexpected treatment medication or procedures,
`demonstrating that this combined therapy is both safe and well-tolerated.
`Of the 15 evaluable patients, 14 (93%) achieved complete responses
`based on physical and endoscopic examination. These results are highly
`encouraging when compared to published rates of complete response
`ranging from 20% to 50% in similar patients treated with irradiation alone.
`5
`5
`Supported by {mClone Systems Incorporated.
`This material was copied
`atthe NLM and maybe
`Subject US Copyright Laws
`
`