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## Complete Summary

#### GUIDELINE TITLE

Liposomal anthracyclines in the management of patients with HIV-positive
Kaposi´s sarcoma.

#### BIBLIOGRAPHIC SOURCE(S)

Systemic Treatment Disease Site Group. Iscoe N, Bramwell V, Charette M,
Oliver T, Zanke B. Liposomal anthracyclines in the management of
patients with HIV-positive Kaposi\'s sarcoma \[full report\]. Toronto
(ON): Cancer Care Ontario (CCO); 2004 Jun \[online update\]. 14
p. (Practice guideline report; no. 12-8). \[15 references\]

#### GUIDELINE STATUS

This is the current release of the guideline.

The FULL REPORT, initially the full original Guideline or Evidence
Summary, over time will expand to contain new information emerging from
their reviewing and updating activities.

Please visit the [Cancer Care Ontario Web
site](http://www.cancercare.on.ca/pdf/pebc12-8f.pdf) for details on any
new evidence that has emerged and implications to the guidelines.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Human immunodeficiency virus (HIV)-positive Kaposi´s sarcoma

#### GUIDELINE CATEGORY

Assessment of Therapeutic Effectiveness\
Treatment

#### CLINICAL SPECIALTY

Infectious Diseases\
Oncology

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

To evaluate whether liposomal anthracycline therapy has advantages over
standard combination therapy for patients with human immunodeficiency
virus (HIV)-positive Kaposi´s sarcoma who have aggressive cutaneous or
visceral disease

#### TARGET POPULATION

Patients with human immunodeficiency virus (HIV)-positive Kaposi´s
sarcoma and good performance status (Eastern Cooperative Oncology Group
\[ECOG\] 0--2) who have progressive cutaneous disease despite prior
treatment with interferon and/or vinblastine, or who have visceral
disease that is symptomatic or progressive

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Treatment**

1.  Liposomal daunorubicin

2.  Liposomal doxorubicin alone or combined with bleomycin and
    vincristine

#### MAJOR OUTCOMES CONSIDERED

-   Survival

-   Time-to-treatment failure

-   Response rates

-   Adverse effects

-   Quality of life

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

**Original Guideline**

The literature was searched using the MEDLINE (Ovid) (1966 through
August 2002), CANCERLIT (Ovid) (1983 through July 2002), and Cochrane
Library (Issue 3, 2002) databases. In addition, the Physician Data Query
clinical trials database, and abstracts published in the conference
proceedings from the meetings of the American Society of Clinical
Oncology (1995--2002), and the European Society for Medical Oncology
(1998, 2000) were searched for reports of new or ongoing trials. The
Canadian Medical Association Infobase and the National Guideline
Clearinghouse databases were searched for relevant clinical practice
guidelines. Relevant articles and abstracts were selected and reviewed
by one member of the Systemic Treatment Disease Site Group (STDSG) and
methodologists, and the reference lists from these sources were searched
for additional trials.

The literature search combined the disease specific terms (sarcoma,
kaposi/ or kaposi:.tw. and HIV/ or HIV.mp. or HIV infections/ or human
immunodeficiency virus.tw. or AIDS/) with treatment specific terms (drug
therapy/ or anthracyclines/ or anthracyclines.mp. or liposome:.and
doxorubicin.mp. or liposome:.and daunorubicin.mp or doxil.tw. or
caelyx.tw. or liposom:.mp. or daunoxome.tw.) with search specific terms
for the following study designs: practice guidelines, systematic reviews
or meta-analyses, reviews, randomized controlled trials, and clinical
trials.

**June 2004 Update**

The original literature search has been updated using MEDLINE (September
2002 through June 2004), EMBASE (September 2002 through June 2004), the
Cochrane Library (Issue 2, 2004), the Physician Data Query database, the
Canadian Medical Association Infobase, and the National Guideline
Clearinghouse, as well as abstracts published in the proceedings of the
meetings of the American Society of Clinical Oncology (2004), and the
European Society for Medical Oncology (2002). Article bibliographies and
personal files were also searched to June 2004 for evidence relevant to
this practice guideline report. Please note that CANCERLIT is no longer
included in update searches: results from an internal Practice
Guidelines Initiative (PGI) project indicated that the overlap with
MEDLINE is 100%, making CANCERLIT database searches redundant.

**Inclusion Criteria**

Articles were selected for inclusion in this systematic review of the
evidence if they met the following criteria:

1.  Randomized controlled trials (RCTs) comparing a liposomal
    anthracycline regimen to observation, placebo, or another
    chemotherapy regimen for the treatment of human immunodeficiency
    virus (HIV)-positive Kaposi´s sarcoma (KS)

2.  Reported data on outcomes of interest including survival,
    time-to-treatment-failure, response rates, adverse effects, and
    quality of life

3.  Trials reporting on patients with aggressive cutaneous or visceral
    HIV-positive KS

**Exclusion Criteria**

1.  Phase I and II studies were not considered, because of the
    availability of randomized controlled trials.

2.  Letters, editorials, and review articles were not included in this
    report.

3.  Papers published in a language other than English were not
    considered.

4.  Trials including only patients with non-aggressive cutaneous KS were
    not considered.

#### NUMBER OF SOURCE DOCUMENTS

Five randomized trials were identified

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Expert Consensus (Committee)

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

Not applicable

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

The treatment and control arms were different in each of the eligible
reviewed trials. The experimental arms of the reviewed trials varied,
with three trials using liposomal doxorubicin, and the fourth examining
liposomal daunorubicin. The control arms also varied, with the
chemotherapy regimens consisting of a combination of doxorubicin,
bleomycin, and vincristine in one trial and liposomal doxorubicin,
bleomycin, and vincristine in one trial. Therefore, it was judged
inappropriate by the Systematic Treatment Disease Site Group to pool the
data by performing a meta-analysis.

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

A preliminary draft of this practice guideline report was circulated to
the members of the Systemic Treatment Disease Site Group (STDSG) for
comment. The discussions at the Disease Site Group (DSG) meetings
highlighted the need to identify the patient group to whom this
guideline was directed. The discussion also focused at some length on
the interpretation of the data. Special care was taken to ensure that
the information was conveyed in a manner that would be helpful to
practitioners. As a result of these discussions, the initial draft of
the practice-guideline-in-progress was modified. The modified version
was recirculated to the STDSG for further comments before being sent for
feedback from physicians involved in the care of patients with human
immunodeficiency virus (HIV)-positive Kaposi´s sarcoma.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

Table 4 in the original guideline document outlines the cost per week
(in Canadian dollars) for treating an average patient with either a
liposomal anthracycline regimen or a combination regimen of doxorubicin,
bleomycin, and vincristine. The acquisition costs reflect only a
component of the costs of delivering therapy. Costs associated with
pharmacy workload and chemotherapy administration need to be considered,
but are beyond the scope of this report. If liposomal anthracycline
therapy is being considered, the direct cost of liposomal daunorubicin
appears more attractive to that of liposomal doxorubicin. However, for
an accurate comparison, detailed cost-effectiveness analyses based on
Canadian data are needed. Unfortunately no such analyses were identified
in the literature.

Two cost-effectiveness analyses, one Swedish and the other American,
were identified. The authors computed the projected cost (in American
dollars) of the two liposomal formulations to achieve similar rates of
response as reported in two of the identified randomized trials. The
authors concluded that despite higher acquisition costs, the costs for
liposomal doxorubicin were actually much lower than those for liposomal
daunorubicin. Given the current price differences between the two
liposomal 11 formulations, the results of the ongoing randomized trial
comparing the two formulations will hopefully clarify the relative
merits of the two agents.

#### METHOD OF GUIDELINE VALIDATION

External Peer Review\
Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

Practitioner feedback was obtained through a mailed survey of nine
practitioners in Ontario (seven medical oncologists and two
hematologists). The survey consisted of 21 items evaluating the methods,
results, and interpretive summary used to inform the draft
recommendations outlined and whether the draft recommendations above
should be approved as a practice guideline. Written comments were
invited. Follow-up reminders were sent at two weeks (post card) and four
weeks (complete package mailed again). The results of the survey were
reviewed by the Systemic Treatment Disease Site Group (DSG).

The practice guideline report was circulated to members of the Practice
Guidelines Coordinating Committee (PGCC) for review and approval. Nine
of eleven members of the PGCC returned ballots. Five PGCC members
approved the practice guideline report as written, and four members
approved the guideline conditional on the Systemic treatment DSG
addressing specific concerns.

The practice guideline report was subsequently approved by the Systemic
Treatment DSG and the Practice Guidelines Coordinating Committee.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

The use of conventional combination chemotherapy or single-agent
liposomal anthracycline therapy represent reasonable treatment options
in the management of patients with human immunodeficiency virus
(HIV)-positive Kaposi´s sarcoma.

#### CLINICAL ALGORITHM(S)

None provided

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The recommendations are supported by randomized controlled trials.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Increased understanding of the efficacy of liposomal anthracycline
therapy compared with standard combination therapy for patients with
human immunodeficiency virus (HIV)-positive Kaposi´s sarcoma who have
aggressive cutaneous or visceral disease

#### POTENTIAL HARMS

In terms of adverse events, rates of severe toxicity and opportunistic
infection appear to be roughly equivalent between liposomal
anthracycline therapy and conventional chemotherapy. However, it is
clear that vincristine and bleomycin contribute significantly to
toxicity, notably neurotoxicity. Therefore, if patients have neuropathy,
or are at significant risk for neurotoxicity, the use of a liposomal
anthracycline agent is a very attractive alternative to the commonly
used combination regimen of doxorubicin, bleomycin, and vincristine.
While not all patients with Kaposi´s sarcoma develop neurotoxicity on
conventional chemotherapy, many are on antiretroviral regimens that may
cause peripheral nerve damage, and many develop signs and symptoms of
neurotoxicity as a result of these therapies.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   Many antiviral regimens used in the treatment of human
    immunodeficiency virus (HIV) cause peripheral nerve damage. In
    patients with HIV-positive Kaposi´s sarcoma, the risk of neuropathic
    toxicity appears to be greater with vinca alkaloid-containing
    conventional treatment regimens than with single-agent liposomal
    anthracyclines. Therefore, if patients have neuropathy, or are at
    significant risk for neurotoxicity, liposomal anthracycline therapy
    may be preferable to conventional combination chemotherapy.

-   Care has been taken in the preparation of the information contained
    in this document. Nonetheless, any person seeking to apply or
    consult these guidelines is expected to use independent medical
    judgment in the context of individual clinical circumstances or seek
    out the supervision of a qualified clinician. Cancer Care Ontario
    makes no representation or warranties of any kind whatsoever
    regarding their content or use or application and disclaims any
    responsibility for their application or use in any way.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Living with Illness

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Systemic Treatment Disease Site Group. Iscoe N, Bramwell V, Charette M,
Oliver T, Zanke B. Liposomal anthracyclines in the management of
patients with HIV-positive Kaposi\'s sarcoma \[full report\]. Toronto
(ON): Cancer Care Ontario (CCO); 2004 Jun \[online update\]. 14
p. (Practice guideline report; no. 12-8). \[15 references\]

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2004 Jun

#### GUIDELINE DEVELOPER(S)

Program in Evidence-based Care - State/Local Government Agency
\[Non-U.S.\]

#### GUIDELINE DEVELOPER COMMENT

The Practice Guidelines Initiative (PGI) is the main project of the
Program in Evidence-based Care (PEBC), a Province of Ontario initiative
sponsored by Cancer Care Ontario and the Ontario Ministry of Health and
Long-Term Care.

#### SOURCE(S) OF FUNDING

Cancer Care Ontario\
Ontario Ministry of Health and Long-Term Care

#### GUIDELINE COMMITTEE

Provincial Systemic Treatment Disease Site Group

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

For a current list of past and present members, please see the [Cancer
Care Ontario Web
site](http://www.cancercare.on.ca/english/toolbox/qualityguidelines/clin-program/systemic-ebs/systemic-dsg/).

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Members of the Systemic Treatment Disease Site Group (STDSG) disclosed
potential conflict of interest information.

#### GUIDELINE STATUS

This is the current release of the guideline.

The FULL REPORT, initially the full original Guideline or Evidence
Summary, over time will expand to contain new information emerging from
their reviewing and updating activities.

Please visit the [Cancer Care Ontario Web
site](http://www.cancercare.on.ca/pdf/pebc12-8f.pdf) for details on any
new evidence that has emerged and implications to the guidelines.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[Cancer Care Ontario Web
site](http://www.cancercare.on.ca/pdf/pebc12-8f.pdf).

#### AVAILABILITY OF COMPANION DOCUMENTS

The following is available:

-   Liposomal anthracyclines in the management of patients with
    HIV-positive Kaposi\'s sarcoma. Summary. Toronto (ON): Cancer Care
    Ontario. Electronic copies: Available in Portable Document Format
    (PDF) from the [Cancer Care Ontario Web
    site](http://www.cancercare.on.ca/pdf/pebc12-8s.pdf).

-   Browman GP, Levine MN, Mohide EA, Hayward RSA, Pritchard KI, Gafni
    A, et al. The practice guidelines development cycle: a conceptual
    tool for practice guidelines development and implementation. J Clin
    Oncol 1995;13(2):502-12.

#### PATIENT RESOURCES

None available

#### NGC STATUS

This summary was completed by ECRI on September 27, 2004. The
information was verified by the guideline developer on October 20, 2004.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions. Please refer to the
[Copyright and Disclaimer
Statements](http://www.cancercare.on.ca/ontariocancernews/copyright.html)
posted at the Cancer Care Ontario Web site.

### DISCLAIMER

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008