Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Tu.B.2217 - Tu.B.2222

Tuesday July 9, 1996

Tu.B.2217
RESOLUTION OF KAPOSI'S SARCOMA ASSOCIATED WITH SAQUINAVIR THERAPY
- CASE REPORT
Workman, Cassy*, Lewis, Craig ", Smith. DO.
*Pnrmary Care Physician; " Unirversity of New South Wales
Objective: A 32yo HIV+ patient with rapid development of Kaposi's Sarcoma (KS) lesions
was found to have resolution of these lesions patient after commencing saquinavir therapy
This case was investigated to determine the association, if any, between resolution of his KS
and aquinavir therapy.
Method: The case was thoroughly investigated paying particular attention to changes in
drug therapy and the tSirnng of the resolution of his lesions. Resolution of lesions was verified by his oncologist. A case report was than prepared.
Results: Resolution of cutaneous KS lesions was found in a 32-year old HIV positive patient
treated with saquinavir. He has no history of other AIDS sentinel diseases. Biopsy proven KS
was first noted n early September 1995 (CD4 count was 40 x 109/mm3).Twelve further
cutaneous lesions rapidly appeared over the next three months (the largest measuring
approximately 2 X I.5 cm with photographic documentation obtained). No visceral KS was
detected and no specfic KS chemotherapy was instigated.Antiretroviral therapy was AZT &
3TC at the time of onset of lesions. Despite changing to 3TC & d4T new lesions continued
to appear and his CD4 count continued to decline.The patient added saquinavir on I
December (I 800 mg daily), with a CD4 count of 30 x 109. His CD4 count rose steadily to
100 by S January 1996. After seven weeks saquinavir therapy ten lesions had completely
disappeared.The two remaining lesions have lost all nodularity and continue to shrink at the
time of writing (now 10% of their original size).
Conclusion: We believe that this is the irst reported case of resolution of KS with
saquinavir therapy and betieve that the clinical mprovement was related to restoration of
immune function as me siured by CD4 count rather than any antineoplastic activity of
saquinavir. We note that the CD4 count at onset of lesions correlated with the CD4 count
at regression. Improverent in HIV related KS has been noted previously with AZT and
more recentlyrtonavi We postulate that resolution of KS occurs when the CD4 count
rises above the count at which lesions initially developed.Testing of this hypothesis must
await observation of a larger patient samrple.
C.Workman, 75 Fitzroy St, Surry Hills, NSW 2010 Australia Tel: [phone], Fax: 61-2 -33 3 c3, email: Ichanare tro.ucc.su.oz.u
Tu.B.2218
OBSERVATION OF VIMENTIN FILAMENT ARCHITECTURE IN CULTURED KAPOSI'S
SARCOMA CELLS.
Payte Paut, Fion,.G University of Ott awa, Department of Microbiology and
Immunology Ottawa. On, CA.
INTRODUCTION: DNA sequences of a potentially novel human gamma herpes virus
have recently been identified in the cells of Kaposis Sarcoma (KS). Isolation of the viral par
ticles has not been successful Infection by herpes viruses often leads to a rearrangement of
the (ytokeletal and nuclear matrix prote ns B cells that are infected with Epstein Barr Virus
(EBV). a gamma herpes v rus, display a re- organization of vimentin filaments within the cells.
Objectives: We hypothS" zed that the presence of a novel human herpes virus in cultured
KS ce lls may use a re organization of the vimentin filament architecture.
Results: Vmentin expresion was assessed in cultures of KS, human fibroblasts, and human
endothelial cells, by imrnunohistochemistry employing immunofluorescent microscopy and
laser corfocal microscopy.The pattern of expression observed in the three cell types was
cons stent with what is pijbished in the literature. No obvious filament re-organization was
oserved in the KS cell however, an increase in the density of vimentin expression was
identified as compared to the endothelial cells and fibroblasts.
Conclusion: No re organirzat ion of vatmentinr filaments was associated with the KS cells,
howeve the increase in ilamenrt density wil serve as an additional marker for the KS phenotylpe.
'. Pyette Department of Microbiology and Immunology Faculty of Medicine, 451 Smyth
Rd Ottawa, On., CAKIH 8M5 6 I 3-562 5800 ext 832 I Fax [phone] E-mail
ppayettecSuottawa.c
Tu.B.2219
PHASE II CLINICAL TRIAL OF LIPOSOMAL DAUNORUBICIN IN THE TREATMENT
OF PULMONARY KAPOSI'S SARCOMA
Saint Marc T, Jeanblanc F., Makhlouf D.,Touraine J.L., Dept. of Immunology pay. P Hfpital E.
Herr iot, 694137 Lyon, Cedex 03 FRANCE
Objectives: to evaluate the efficacy safety and tolerance of liposomally encapsulated
Dur or aubicir (DaunoXorieo,Vestar) n the treatment of advanced AIDS related pulmonary Kaposi's Sarcoma.
Methods: Eleven HIV po itive individuals with proven pulmonary KS were enrolled into the
study 6 patients had min mal cutaneous KS and the remaining 5 had extensive cutaneous
KS.7 patients had a pror h5io of opport s infection and 7 out of II patients had
bee prevously treted with systomic chemotherapy and had progresed The median entry
CD4 lymphocyte count was 52/mm3. DaunoXome was dnciistered intavenously every
2 weeks it i dose level of 40m/m2. All patients received concorent antiretrovial therapy
(AZ. Dt Dt C). Patients were evaluated for response (complete, partial, stable or progression) very month' (udged by bronchoscopy chest X-ray thoracic computed tomograph ), quality of life, dru. toxicity immune fur ti
Results: patients rceceived between 4 and 25 cyles of therapy (median 14) with cumulative
dosages of 400 2500m: 4 patents received core than 8 cycles (18 25), 3 patients
between 12 snd 8, 4 Sn than 6 cycles. After 3 months of therapy 2/ I patients had a
complete response, 5/ I achieved partial remission and 3/I I had stable disease, and I/ I
showed pulmonary KS progression. 8 patients have been discontinued from the protocol to
date 3 patients had severe pulmonary KS progression (2 deaths) after 6, 15 and 20 cycles
of therapy, 5 patients had progress ye HIV disease and I patient withdrew for personal reasons after 6 cycles. 2 patients contnue to be treated. 7/ I patients experienced new cutaneous ens, under treatment. DaunoXome was well tolerated and symptoms were min
mal,nd infrequent.Toxcty s observed included mild delayed nausea, fatigue (transient),
infrequent mld to mode ate granuo-cytopenia (500-1000 cells/mm3). Anemia was

uncommon. 8/ I patients were placed on intermittent low dose Gm C-CSF after break
through episodes (maximum 3 days every 14 days). 148 cycles of treatmrent were given n
all. In 2 patients the dose was reduced by 50% and the treatment was delayed by weeks
n one patient because of hypereosnophylia, and by I week in another one pitient because
of opportunistic infection. Importantly dose delayed was associated with pro pgreson of KS.
Conclusions: liposomal daunorubicin may be a promising alternative to the chemotherapy
protocols in current use. Hematological tolerance is good and side effects overall mnimei.
T Saint Marc, Dept. of Immunology - pav. P Hopital E. Herriot, 69437 Lyon cedex 03,
FRANCE
Tu.B.2220
TREATMENT OF AIDS-RELATED KAPOSI'S SARCOMA (AIDS-KS) WITH
ALLTRANS-RETINOIC ACID (ATRA). RESULTS OF A PHASE II TRIAL
Saia, Philipe, Pavlovic M*, Chastang C''", Fauveau V". Favre-Meh-arzi, Nicolas J
Chenon A). Groupe Kaposi de I'Agence Nationale de Recoherhes surle SIEDA "Servce de
Dermaologie, Hbpital A Pare, Boulogne. '"DBIM, Hlpital St Louis, Laboratocres de
Virolog e. 'Hpital Rotschild and IH'pital Trousseau, Pans, France
Objectives: I)To evaluate the efficacy and safety of oral ATRA in patientr ath low risk
AIDS-KS. 2) To investigate in vivoe its effect on HIV replicaton.
Methods: Prospective, open-label, non-randomized multicenter tr iCriteia for inclusion:
(a) HIVI seropositivity; (b) low-risk KS (TO 10 SO in the classification of AIDS Clnical Tna1s
Group(ACTG)); (c) > 200 CD4/ml;: (d) at least 4 measurable KS lesions. Ma n citer-a for
non-inclusion was systemic treatment of KS. Antiretrovirals were allowed if initiated 4
months prior to inclusion.ATRA was given orally 45 mg/m2/d for 3 months. Clinical and
laboratory evaluations were performed at day (D)-30, DO. D 5. D30, 45, D60. D75, and
D90. Main cnteria of efficacy was complete (CR), partial (PR) response, progression (P), and
stable disease (S) evaluated according to ACTG cr teria. In all patients CD4 posite cells
counts and plasma P24 antigen were measured. In 9 patients we ilso performed cellular
viremia in peripheral blood mononuclear cells, plasma viremia, plasma HIV RNA (sec
quantitative RTPCR assays). and plasma HIV RNA (branched-DNA).
Results: 20 male patients, 35.2+7.5 years- old, with a CD4 level of 309 + 04 CU/nl, were
included. Six patients were on antiretroviral therapy Response w cs observed after ait east 8
weeks n most patients. It consisted of flattening and clearing of the lesons. At D90 PR was
observed in 8 (40%), S in 8 (40%) and P in 4 patients (20%). In 6 of 8 patents with PR
who pursued ATRA, further improvement was observed.The rmnot frequent adverse effects
were chilitis (95%), transient headaches (60%), mild hypertnghcendemi, (60%) and skin
dryness (45%). No patient came off therapy for severe adver se drug reaction. No snficant
changes in CD4 lymphocyte counts was observed during treatncct. HIV vir lmur caiquan
tification by currently recommended techniques suggested the absence of snior ',f
HIV replication by ATRA.
Conclusion:Treatment of low-risk AIDS-KS by ATRA 45 mg/n d orally was w-l 'molerated
and could be given for prolonged durations. It induced afterait least 8 weeks on therapy PR
or S in most patients.The absence of stimulation or inhibition of IIV rephication by ATRA n
vivo in man suggests that it may be administered in HIV-nfected patients
P Saiag, Dermatologie, Hopital A Pare, 9, avenute Charles de Gaulle, 92 104 Boulogne
France. Phone: (I) 49 09 56 73, Fax: (I) 49095685, e mailsaiag-paophop-pas.fr
Tu.B.222 I
LIPOSOMAL DOXORUBICIN IN PULMONARY KAPOSI'S SARCOMA: IMPROVED
SURVIVAL AS COMPARED TO PATIENTS WITHOUT LIPOSOMAL DOXORUBICIN
Gruenaug. M, Bogner JR, Loch O. Goebel F- D: Medizinische Pol klnik K linikum Innenstdt,
University of Munich, Germany
Background: Pulmonary Kapos's Sarcoma (KS) has been characterised by a poor- prognosis.
According to data from the literature and own observations survivl nges m m 2 to 6
months after diagnosis.
Objective: To evaluate survival in patients (pts) with pulmonary KS in patients treated with
liposomal Doxorubicin (LD) and to compare it with patents without therapy and/or with
other chemotherapy regimen.
Patients and Therapy: Group I (n/ 2 1): pts treated with LD (as part of a mult center trial)
including 9 pts pretreated with other compounds. Group 2 (n -8): pts who never received
LD.This group included 4 pts who received conven% surviving tional therapes (Bleomycin and/or mncrstne) and 4
patents without chemotherapy. Ail participants
0 with liposomal
ma Dox....ubicin were maie The mean age was 38.: - 7.7 year-s TIS
0 stagn o KS wasTIII SI n 23,T1105I r S uand
a p<0o.oo05 T I I SO in 3 pts, respectively. Diagnostic workup.. ithout included rid o7raphy, co lputed tomo a' a mmand
2 bronchoscopy. On onfirmed pulrior KS ses
0 5 10 15 20 25 30 were considered in thms analysis.
months after diagnosis of pulmonary KS Results: Saurvi at ar nalysis by Kapln Mee plot
showed a signiicant beneit for patients wth LD
treatment (figure). Mean survival times were +6.75 months (group m rse I7 3 pt
alce) versus 4 + 6.26 months (group 2; 0 17; no pts live).The dfer-enc ws onimed
when the 4 pts without any chemotherapy were excluded f6om ana sis Aver e CD4 ev
els did not differ significantly at KS d agnos s. Clinical response inc uded mprpo 't
cough and dyspnea, improvement of arterial pO2 and radIorpphc KS ptli
Conclusion: Our analysis suggests clear survival benefit for pients with pulmoury KS on
liposomal Doxorubin.
Gruenaug. Michael Med.Poliklinik, University of Munich, PettenkoIerstrasse 8a, 80336
Munmch, GermanyTel ##49 89-5 603573 Fax ##[phone]
Tu.B.2222
ALPHA INTERFERON (IFN) PLUS ZIDOVUDINE IN KAPOSI SARCOMA:
A RANDOMIZED TRIAL COMPARING IFN 3 MU VS. 10 MU DAILY.
Podzarczer Daniel, Gonzzilez Lahoz (, Inchaustegu L. Alegre MValenca E. Alsina M. Santn
M, Roca V, KS Study Group
Objective:To evaluate the eficacy and safety of two regimens of IFN in the treatment of
non-visceral AIDS-associated Kaposi sarcoma (KS),

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