THIRTY-FOURTH
`
`Annual Meeting of the
`
`§
`
`g 2%
`
`American Society of Clinical Oncology
`
`May 16 _ 19, 1998
`
`PROGRAM/PROCEEDINGS
`
`Los Angeles, California
`
`
`
`Contents
`
`ASCO Program Information
`in
`Officers and Directors ...........................................................
`iv
`Calendar of Events ...........................................................
`in
`Committee Rosters ...........................................................
`xn
`General Information ..........................................................
`xv:
`Award Recipients ............................................................
`xvii
`1998 ASCO Merit Awards .......................................................
`xviii
`Plenary Session ..............................................................
`:1:
`Integrated Symposia ..........................................................
`xx
`Special Sessions .............................................................
`xxiii
`Annual Business Meeting .......................................................
`xxiv
`'Ihmor Panel Sessions .........................................................
`Scientific Sympoeia ........................................................... xxvii
`Education Sessions ........................................................... xxviii
`Meet the Professor Sessions ..................................................... mo'ii
`1998 Annual Meeting Support .................................................... xxxvii
`1998 ASCO Exhibitor List ....................................................... xxxviii
`ASCO Shuttle Service .........................................................
`xl
`Los Angeles Convention Center Maps ...............................................
`xliii
`Scientific Program .............................................................
`xlv
`ASCO Proceedings .............................................................
`1a
`Plenary Session ..............................................................
`18
`Adult Leukemia and Lymphoma ..................................................
`2a
`ADDS/Supportive Care .........................................................
`41a
`Bone Marrow ’I‘ransplantation/Cytokines ............................................
`75a
`Breast Cancer ...............................................................
`97a
`Clinical Pharmacology ......................................................... 185a
`Gastrointestinal Cancer ........................................................ 255a
`Genitourinary Cancer ......................................................... 307a
`Gynecologic Cancer ........................................................... 3493
`Head and Neck Cancer and CNS .................................................. 378a
`Health Services .............................................................. 413a
`Immunobiology and Biologic Therapy ............................................... 4288
`Lung Cancer ....................................
`‘. . -‘
`................. 460a
`Melanoma and Sarcoma ..................... q 233335 1| 3‘
`‘4
`................. 505a
`Pediatric Oncology......................... 3b
`.‘.L
`J
`‘ I
`_ ................. 525a
`'Ihmor Biology/Human Genetics................
`8,93 211421135
`..................... 547a
`
`(cid:43)(cid:82)(cid:86)(cid:83)(cid:76)(cid:85)(cid:68)(cid:3)(cid:89)(cid:17)(cid:3)(cid:42)(cid:72)(cid:81)(cid:72)(cid:81)(cid:87)(cid:72)(cid:70)(cid:75)
`Hospira v. Genentech
`IPR2017-00805
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`Genentech Exhibit 2025
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`
`1
`
`

`

`I 920
`
`CLINICAL PHARMACOLOGY
`
`CLINICAL PHARMACOLOGY
`Clinical Pharmacology III
`General Poster Session. Tuesday. May 19. 1998
`
`‘739
`A PHASE I AND PHARMACOKINETIC (PK) STUDY OF DOCEI’AXEL IN CANCER
`PATIENTS (PTS) WITH LIVER DYSFUNCTION DUE TO MALIGNANCIES. fl
`Baker, P. Ravdi'n, C. Aylesworth. L. Smetzer. R. Bruno, L. Verni'llet. R.
`Pazdur, 6. Doyle. L. Hammershai'mb. E. Hooker. H. Burris, G. Eckhardt. 7'.
`Johnson. M. Kraynak. L. Hammond, G. Rodnguez. G. Weiss, D. Von Hoff. &
`E. Rowinsky. Cancer Therapy & Research Center, San Antonio. TX. MD
`Anderson, Houston. TX and Rhone-Pau/enc Rorer. CollegeviI/e, PA &
`Antony. France.
`Docetaxel. a semisynthetic taxoid. undergoes extensive metabolism by
`cytochrome P-450 3A4 and biliary excretion. In phase II trials. 3 popula
`tion PK evaluation revealed that pts with elevated alkaline phosphatase
`(AP) (>25 ULN) and SGOT and/or SGPT (> 1.5 ULN) had a 30% decrease
`in mean docetaxel clearance which was associated with an increased risk of
`severe toxiCity (Proc. ASCO 14:457;1995). This study was performed to
`determine the MTD and PK profile of docetaxel in cancer pts with varying
`degrees of tumorirelated liver impairment. Pts were enrolled into one of 3
`groups:
`(1) Tbili 21.5 to <30 ULN with any AP and transaminase
`elevation. (2) Tbili 23.0 ULN with any AP and transamiiiase elevation, and
`(3) Tbili 51.0 ULN with elevated SGOT and/or SGPT(>1.510 55.0 ULN)
`and AP (>2.5 to $5.0 ULN). The starting dose for all groups was 40 mg/m2
`(1 hr infusion) every 3 weeks. To date. 13 patients. 11 of whom have liver
`metastases. were treated with 30 courses at 40 mg/m2 (3 pts each in
`groups 1 and 2, and 1 of in group 3) and 60 mglm? (3 pts each in groups 1
`and 2). Docetaxel 40 mg/m2 was well tolerated by pts in all groups. At 60
`mg/m2. DLT occurred in 1 pt in group 1 (ANC < SOD/(LL with infection)and
`2 pts in group 2 (gr 3 mucositis). although 1 of these pts received prior RT
`to the external biliary ducts and was replaced. Pt accrual has been
`expanded at 60 mglm’ for groups 1 and 2. A 3-compartment linear model
`was used to determine the following preliminary PK estimates:
`No. of
`Dose
`Cmax
`AUC
`Cl
`
`Group
`Pts
`(mg/m2
`(pg/mL)
`(pg'hrlmL)
`(Uhr/m2
`1
`2
`40
`1.5.1.7
`2.4.6.2
`16.8. 6.5
`1
`60
`3.9
`7.6
`7.9
`2
`40
`0.69.1.4
`1.1.2.3
`37.7. 17.1
`2
`60
`3.1. 3.7
`6.1.6.7
`9.8.8.9
`1
`40
`1.3
`2.7
`15.0
`
`2
`
`3
`
`In the majority of patients in groups 1 and 2. higher AUC values were
`observed at 60 mg/m2 than 40 mg/m2. which may have contributed to
`differences in toxicity at the 2 dose levels. In these patients, AUC values
`achieved at 60 mg/m2 appear to be similar to those at 100 mg/m2 in
`patients with normal liver function parameters (J. Clin. Oncol. 13:2643:
`1995).
`
`Proceedings of ASCO Volume 1 7 i 998
`
`*740
`LONSJERM WEEKLY PAcuTAXEL (P) IN METASTATII: BREAST CANCER (MOO).
`A PHASE II TRIAL IN PRETREATED PATIENTS (PTS). 5. Breier, C. Lebedinsky.
`C. Ayivr'ri, C. Raf/é, G. Trains, C. Cot, P. Pol/ti. Hospital Israel/ta, Buenos
`Aires, Argentina.
`‘
`
`Long—term therapy with short infusions of P is limited by myelosuppression
`and cumulative neurotoxicity. In order to allow prolonged treatment with P
`in pts with MBC. the actiwty and toxicity of a weekly infusion of P was
`studied. Twenty-four ambulatory pts with measurable MBC. previously
`treated with chemotherapy (5 pts adjuvant. 7 pts neoadjuvant. 18 pts
`metastatic} received F (80 mg/m2 over 1 hr) every week until disease
`progression or limiting toxicny. Dexamethasone 4 mg, diphenhydramine 30
`mg, and ranitidine 50 mg were given l.\/. immediately prior to each dose of
`P. EMS and neuro exam were performed at baseline and at least every 6 and
`3 months, respectively. All pts gave written informed consent. Pts charac-
`teristics were: median age: 55 (35—77), PS: 0—2. pre/postmenopausal:
`10/14 pts. Sites of metastatic disease (‘16) included liver (25), bone (38).
`lung (46) and soft tissue (50). Number of metastatic sites: 1 (50%), 2
`(29%). 3 or more. (21%). A total of 595 weekly doses were delivered, with
`a median of 25 doses per pt (5—55). Median cumulative dose was 1980
`mg/m2 (400—4400). median delivered dose intensity: 78 mg/mZIwk
`(72—80), 97% of planned. The overall response rate was 12/24 (50%. 95%
`CI: 30—70). CR: 2124 (8%). PR: 10/240125). SD: 5/24 (21%). PD: 7/24
`(29%). Median time to progression: 9 months (2—18). median survival: 17
`months (2—25). Toxicity (NCl criteria): No Grade 4 toxmity was observed.
`Grade 3 W80: 1 pt. The mean ganulocyte nadir was 1783luL (1078—
`2970). No febrile neutropenia. no septic deaths. One admission due to
`DVT. There was no Grade 3—4 nonhematologic toxiCity. except alopecia (9
`pts. 38%). Onycholysis/onychomycosis was noted in 7 pts (29%). skin rash
`in 2, Grade 1 nausea in 3 (13%). No maior hypersensitivity. The worst
`neuropathy was Grade 2 (4 pts). EMG showed axonopathy in 5 pts.
`Concusions: Long-term weekly P is active and well toierated in MBC. This
`schedule allows a high cumulative dose of P without major myelo- or:
`neurotoxlcity. This weekly regimen deserves further exploration.
`
`'741
`DEPOSITION OF PACLITAXEL INTO NORMAL ANO MALIENANT BRAIN TUMOR
`TISSUE. R.L. Fine, C. Balmaceda, 1. Bruce. J. Hall. C. Hesdorffer, M. Sisti,
`M. Huang, MR. Fete/I. Columbia University College of Physicians and
`Surgeons, New York, NY.
`In vitro, paclitaxel demonstrates marked antitumor activity against human
`glioblastoma celt lines. However, in vivo paclitaxel has minimal activity
`against newly-diagnosed giioblastoma (Fetell et al: J Clin Oncol 15:3121—
`3128. 1997). One possible explanation is poor paclitaxel deposition into
`the brain tumor because of
`the blood brain barrier
`(BBB) and P-
`glycoprotein (ng). Our preclinical studies in rats bearing 66 gliomas
`demonstrated that a ng inhibitor. tamoxifen. increases the deposition of
`paclitaxel into rat biain tumors by as much as 400%.
`In our clinical studies. we treated patients with recurrent primary brain
`tumors or brain metastases who required surgical resection as the next
`appropriate treatment. Six patients received paclitaxel 175 mg/rn2 between
`12 to 18 hrs prior to resection; three of these patients also received high
`dose tamoxifen. At surgery. samples of tumor tissue (T). brain adjacent to
`tumor (BAT). normal brain (NL). and serum were measured by reverse
`phase HPLC for paclitaxel and tamoxifen. Mean tissue paclitaxel levels
`(ng/g) for T were 1078 (187-2135). BAT 739 (36-2116) and ML 362
`(42—945). Mean serum paclitaxel
`levels (ng/ml) at surgery were 90.4
`(47-165). There was no increase in paclitaxel tissue levels in patients who
`received tamoxifen. however serum levels were 2.1 mM (Ll—3.2). below
`the therapeutic level for ng inhibition.
`These Pralimmary data suggest that paclitaxel penetrates and accumulates
`in brain tissue in the following order; T > BAT > NL. Conclusions about
`tamoxifen's effectiveness for increasing paclitaxel penetration into brain
`tumors are still being assessed utilizing higher tamoxifen doses.
`
`2
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`