Thirty-Fifth
`Annual Meetingof the
`American Society of Clinical Oncology
`May 15-18, 1999
`Atlanta, Georgia
`Program/Proceedings
`
`
`
`Copyright 1999 American Society of Clinical Oncology
`
`é
`
`BIT
`
`2024
`
`EXH! :
`
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`Hospira v. Genentech
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`IPR2017-00805
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`Genentech Exhibit 2024
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`Proceedings of ASCO Volume 18 1999
`242
`
`Low Dose Oral Famciclovir ts Adequate Herpes Simplex Virus Prophylaxis in
`Patients Undergoing High Dose Therapy and Autologous Stem Cell Rescue.
`Rod E. Quilitz, Jorge G. Avila, John N. Greene, Steven C. Goldstein, Karen
`K. Fields. 8MT Division, H. Lee Moffitt Cancer Center, Tampa, FL.
`More than 70% of herpes simplex virus (HSV) seropositive patients (pts)
`undergoing bone marrow transplantation will experience reactivation oforal
`or genital HSV lesions. Prophylaxis with oral or intravenous (!V) acyclovir
`has become the standard of care. Recently, famciclovir has become an
`alternative to oral acyclovir. It has the advantage of less frequent oral
`dosing, twice per day (Q8H) compared to =3 times/dayin pts treated with
`oral acyclovir. The optimal dose in pis undergoing autologous stem cell
`transplantation (ASCT) has not been defined. We evaluated the role of
`famciclovir as HSV prophylaxis in all pts that were HSV IgG seropositive
`undergoing high dose therapy (HDT) and ASCT. A total of 67 such pts with
`predominately breast cancer,
`lymphoma, and myeloma were studied
`between 10/97 and 8/98. All pts received famciclovir, 125 mg BID,
`starting at the initiation of HDT and continuing through engraftment (an
`absolute neutrophil count of 500/uL) or until complete resolution ofall oral
`or genital lesions that persisted beyond engraftment. If pts became unable
`to tolerate oral medications. IV acyclovir, 250 mg/m2 QSH was substituted.
`Reviewof all positive HSV cultures during this time revealed only 1/67 pts
`(1.5%)receiving prophylactic famciclovir developing a breakthrough cul-
`ture positive lesion. This was an oral lesion that developed on day +2 of
`transplant and responded to IV acyclovir, 250 mg/m2 Q8H. No other
`Clinically significant HSV infections were seen. We conclude that famciclo-
`yir, 125 mg orally BID, beginning with HDT and continuing through
`engraftment, provided adequate prophylaxis of oral and genital HSV
`infections. Higher dosesof famciclovir may be necessary for pts undergoing
`more immunosuppressive regimens such as allogeneic transplantationorin
`pts with documented HSV infections.
`
`BONE MARROW TRANSPLANTATION/CYTOKINES
`
`65a
`
`243
`
`Increasing CD34+ Cell Doses Reduce Hematopoietic Recovery Period and
`Supportive Needs After High-Dose Chemotherapy (HDC) and Peripheral Stem
`Cell Support (SCS) in Patients (pts) with Solid Tumors. Ramon Salazar, Claudi
`Sola, Pablo Maroto, Jesus Montesinos, Jose J. Sanchez, Elena Cabezudo,
`Milva Rodrigez, Judith Balmafia, Carles Pericay, Amaya Ramirez, Beatriz
`Pardo, Eduard Muftiz, Clara Martinez, Joan Brunet, Jose A. Cancelas, Juan
`J. Lopez. Blood Bank, Sant Pau Hospital, Barcelona, Spain.
`We analyze CD34-+ cell dose influence on hematopoietic recovery and
`supportive requirements after HDC. Two hundred and one pts (breast
`cancer 165, lymphomas 11, ovarian 10, others 15} with a median (M) of 6
`(3-24) cycles of previous chemotherapy (CT) were mobilized with G-CSF 10
`ue/Ke/d (138pts, 69%), CT+G-CSF (60 pts, 30%) or both (3pts, 1%). A
`minimum of 2.51068 CD34+ cells/Kg was collected by leukapheresis
`(LK). G-CSF was administered to 82 pts from d-O and 106 pts from d+5
`following SCS. RESULTS: M age was 43yrs (17-63). A Mof 2 (1-7) LK per pt
`was performed with a collection of 6.5 (2,5-44.4) 10®CD34+ cells/Kg. A
`M of 6.4 (2.5-42.7)x 106 CD34+ cells/Kg was reinfused. The M recovery
`days to 0.5109 neutrophils (NtIL was 9 (7-16) and to 20x 109platelets
`(PitVL 11 (7-35). Two pts died, one of diffuse alveolar hemorrhage and one
`of ARDS. The number of CD34-+celis/Kg infused had an inverse correlation
`with recovery days to 0.5109 Nti/L and 20109 Pit/L (R= -0.31 and
`-0.13; p<0.05) reaching a plateau at 13x 10°CD34+ cells/Kg, which was
`confirmed by multivariate analysis. Requirements of supportive measures
`weresignificantly lowerin pts given a higher dose of CD34 + celis/Kg.
`2.5-5x10® 5-10x106 >10x10®
`
` CD34 +cells/Ke (56pts) (107pts) (36pts) p:
`
`
`
`M days ToO0.5x10°NtL 9
`(8-16)
`9 (7-14)
`8 (7-12) 0.000
`To 1x10? NtlvL
`10
`(9-27)
`10 (8-23)
`9 (7-14) 0.000
`To 20 109 PIVL
`13 (10-34) 11.5 (7-14) 10 (7-12) 0,000
`To 50x 109 PIt/L
`15 (10-44)
`13(10-34) 12 (8-38) 0.000
`To 100 109 PIt/L
`21(13-365)
`=—-17(11-64) 14(12-50) 0.000
`N. Pit transf.
`3
`(1-34)
`2 (1-23)
`2 (1-15) 0.01
`N. Plt units transf.
`22 (7-235)
`18(6-141) 15(5-141) 0.002
`
`
`CONCLUSIONS: In the range of 2.5-13x10® CD34— cells/Kg, increasing
`CD34+ cell dose determine a more rapid hematopoietic recovery and a
`decrease of required supportive measures.
`
`244
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`245
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`High-Dose Chemotherapy Supported By Refrigerated Peripheral Blood Stem
`Celt Transplantation for Cervical Carcinoma. Sobrevilla P Lara F, Zinser J,
`Solorza G, Gonzalez EA, Robles J, Lépez GC, Hinojosa LM, Mufioz D, Mota
`A, de la Garza SJ, Mota A, Duefias A. From the inst. Nac. Cancerologia,
`MexicoCity.
`The prognosis of cervical cancer patients has not been improved in the last
`decades, Sofar, standard-dose chemotherapy (SDCT)hasfailed to increase
`the survival either as adjuvant or neoadjuvant modality. To explore the use
`of high-dose chemotherapy (HDCT), from Dec 92 to Dec 95, five patients
`with untreated early and locally advanced cervical carcinoma were treated
`with HDCT and refrigerated peripheral blood stem cell support using the
`ICE program (ifosfamide 10g/m2 plus Mesna at 100% of the Ifosfamide
`dose; Carboplatin at 1.5 g/m2 and Etoposide 2.1 g/m2). Three stage IB (2
`squamous, 1 adenosquamous) patients received 3 courses of SDCT
`followed by HOCT in an adjuvantsetting after radical hysterectomy and
`pelvic lymph-node dissection. Following HDCT they received standard
`postoperative radiation. The 2 patients staged IB (1 squamous,
`1
`adenosquamous) received neoadjuvant SOCT and then HDCT,after surgery,
`they underwent standard radiotherapy. The treatment was well-tolerated,
`all patients had rapid hematologic recovery being the most frequent
`complications grade 3 mucositis and neutropenic fever. The three patients
`adjuvantly treated are disease-free at 31, 41 and 50 months of follow-up.
`Both stage IIB patients achieved a clinical response of 95% beingative
`and well one of the these two patients at 60 months. The rernaining patient
`however, had systemic progression despite the excellent response at the
`primary tumor. Our results show that adjuvant HDCT could reduce the
`likelihood of relapse in high risk patients, and that it can increase the
`resectability rate of patients with locally advanced disease. HDCT deserves
`a formal evaluation on high-risk and locally advancedcervical cancer.
`
`PhaseII Study of Weekly Paclitaxel (P) Treatment in Recurrent Breast Cancer
`
`After High-Dose Chemotherapy (HDC). C Sola, A Liuch, J Garcia-Conde,
`R Salazar, T Garcia, J Montesinos, R Vera, M Benavides, MA Climent, J
`Homedo,
`| Alvarez, F Présper, H Cortés-Funes, JJ Lépez Lopez. SOLTI
`group. Spain.
`Weevaluate efficacy, toxicity and feasibility of l-hour weekly P in pts with
`relapsed breast cancer after HDC with stem cell support. From June 1996
`to October 1998 P 80 mg/m? weekly was administered to 40 pts.
`Premedication consisted of dexamethasone 10 mg, diphenhydramine 50
`mg and ranitidine 50 mg. They had received one cycle of HDC and amedian
`(M)of 6 (3-12) cycles of conventional chemotherapy. All pts had received
`anthracyclines and none taxanes. The M time from HDC to relapse was
`11.5 (2-72) months. A neutrophil count =1 x 109/L and platelet count
`=75 x 10%L were required. M Karnofsky index and age were 80%
`(70-100) and 50 years (32-60). Pts had a M of 2 (1-5)sites of metastatic
`disease: 20 predominant viscera! disease and 20 nonvisceral. RESULTS:
`Forty pts were assessable for toxicity and 28 with measurable disease for
`response. A total of 694 cycles of P were delivered, with a M of 18 (2-27)
`perpt. The initial planned dose-intensity could be achieved, only 30 cycles
`(4%) were delayed without dose reductions. The main toxicities were
`neutropenia (WHO Grade | + Il: 34% of cycles, Gill: 4%, GIV: 1%) but
`without associated febrile episodes; thrombopenia (GI + II: 8% of cycles;
`GIlf: 1%); anemia (Gf + I: 75% of pts; GI: 2%); peripheral neuropathy
`(Gi: 36% of pts; Gil: 15%; Gil: 6%). One pt discontinued P due to
`neuropaty GIII after 14 cycles. There were 8 CR and 11 PR for an overall
`responserate of 19/28: 68% (95% Cl, 58% to 78%)with an actuarial M of
`time to progression of 10 (95% Cl, 7-14) months. Sites of disease in
`responding pts were: lymph nodes in 10, lung 9, skin-soft tissue 7, liver 4,
`bone 5, pleura 2. CONCLUSIONS:This schedule provides a dose-intensive
`P delivery with a favorable toxicity profile and a promising activity in
`recurrent breast cancer after HDC and anthracyclines.
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`245
`
`PhaseIl Study of Weekly Paclitaxel (P) Treatment in Recurrent Breast Cancer
`After High-Dose Chemotherapy (HDC). C Sofa, A Liuch, J Garcia-Conde,
`R Salazar, T Garcia, J Montesinos, R Vera, M Benavides, MA Climent, J
`Homedo,
`| Alvarez, F Présper. H Cortés-Funes, JJ Lopez Lopez. SOLT!
`group. Spain.
`We evaluate efficacy, toxicity and feasibility of 1-hour weekly P in pts with
`relapsed breast cancer after HDC with stem cell support. From June 1996
`to October 1998 P 80 mg/m? weekly was administered to 40 pts.
`Premedication consisted of dexamethasone 10 mg, diphenhydramine 50
`mg and ranitidine 50 mg. They had received one cycle of HDC and a median
`(M) of 6 (3-12) cycles of conventional chemotherapy. All pts had received
`anthracyclines and none taxanes. The M time from HDC to relapse was
`11.5 (2-72) months. A neutrophil count =1 x 10%/L and platelet count
`>75 x 10%L were required. M Karnofsky index and age were 80%
`(70-100) and 50 years (32-60). Pts had a M of 2 (1-5) sites of metastatic
`disease: 20 predominant visceral disease and 20 nonvisceral. RESULTS:
`Forty pts were assessable for toxicity and 28 with measurable disease for
`response. A total of 694 cycles of P were delivered, with a M of 18 (2-27)
`per pt. Theinitial planned dose-intensity could be achieved, only 30 cycles
`(4%) were delayed without dose reductions. The main toxicities were
`neutropenia (WHO Grade | + {Il: 34% of cycles, GIII: 4%, GIV: 1%) but
`without associated febrile episodes; thrombopenia (GI + Il: 8% of cycles;
`GH: 1%); anemia (GI + Il: 75% of pts; GUI: 2%); peripheral neuropathy
`(Gi: 36% of pts; Gil; 15%; GIIl: 6%). One pt discontinued P due to
`neuropaty Gilt after 14 cycles. There were 8 CR and 11 PRfor an overall
`response rate of 19/28: 68% (95% Cl, 58% to 78%) with an actuarial M of
`time to progression of 10 (95% Ci, 7-14) months. Sites of disease in
`responding pts were: lymph nodesin 10, lung 9, skin-soft tissue 7, liver 4,
`bone 5, pleura 2. CONCLUSIONS: This schedule provides a dose-intensive
`P delivery with a favorable toxicity profile and a promising activity in
`recurrent breast cancer after HDC and anthracyclines.
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