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In Reply:

Memorial Sloan-Kettering Cancer Center, New York, NY

Drs Nasti and Tirelli address the question of which patients with AIDS-associated Kaposi's sarcoma (KS) who are not already receiving effective highly active antiretroviral therapy (HAART) should be considered candidates for immediate cytoreductive therapy, before the effects of HAART on KS can be assessed. Although I agree in part with their recommendations, I suggest that a more individualized approach be adopted that goes beyond the categories included in the AIDS Clinical Trials Group KS staging system¹ or their recently suggested modifications.²

In their reanalysis of the AIDS Clinical Trials Group staging system in the HAART era, Nasti et al² identified two groups of patients with a significantly shortened 3-year survival and for whom they now recommend concurrent institution of HAART and chemotherapy, without awaiting a response to HAART alone. The first group included patients with any of the poor-risk tumor features (T1; ie, extensive oral KS, tumor-associated edema, tumor ulceration, or visceral KS) who also had evidence of advanced HIV-related systemic illness (S1; ie, history of opportunistic infection, lymphoma-like "B" symptoms, other HIV-related illnesses, or a Karnofsky score below 70). The second group, a subset of patients with T1 tumors, included patients with pulmonary KS (designated Tp1), irrespective of the presence (S1) or absence (S0) of HIV-related systemic illness.

For the latter group, their data suggest that shortened survival is a direct consequence of pulmonary KS. For such patients, I agree that institution of cytoreductive therapy is warranted, without waiting to see if the tumors regress with HAART alone. For patients with T1 tumors without lung involvement (Tp0) who also had signs and symptoms of advanced HIV disease (S1), the increased hazard ratio for death compared with S0 patients is likely a consequence of advanced HIV infection rather than KS progression. For such patients, and others who do not meet the T1 criteria (eg, those with extensive or disfiguring cutaneous KS), I believe that the decision to institute cytoreductive therapy before assessing the effects of HAART should be based on KS-related symptoms that result in adverse effects on physical or social functioning rather than solely on the presence of HIV-related systemic illness. Although for purposes of my analysis of the published data on HAART-associated KS regression, which rarely included information on KS-related symptoms, I equated T1 with advanced, symptomatic KS, but also indicated that tumor stage was an imperfect surrogate because some patients with T1 disease have no KS-related symptoms, whereas others with T0 disease might be highly symptomatic.³

Of the 47 deaths reported by Nasti et al,² 33 (70%) were attributed to progressive KS, but the contribution of chemotherapy (which was given to 69 of 211 patients) to survival was not analyzed and the causes of death within each stage group were not given. The poorer survival of patients with Tp0S1 disease cannot be used to justify the use of chemotherapy in all patients in this category in the absence of data indicating that chemotherapy for KS has a positive influence on survival. Until such data are forthcoming, the justification for chemotherapy is its ability to induce more rapid palliation of KS-related symptoms than HAART, which generally requires many months to achieve maximal KS regression.

Author's Disclosures of Potential Conflicts of Interest

The author indicated no potential conflicts of interest.

REFERENCES

1. Krown SE, Testa M, Huang J: AIDS-related Kaposi's sarcoma: Prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol 15:3085-3092, 1997[Abstract]

2. Nasti G, Talamini R, Antinori A, et al: AIDS-related Kaposi's sarcoma: Evaluation of potential new prognostic factors and assessment of the AIDS Clinical Trial Group staging system in the HAART era—The Italian Cooperative Group on AIDS and Tumors and the Italian Cohort of Patients Naïve from Antiretrovirals. J Clin Oncol 21:2876-2882, 2003[Abstract/Free Full Text]

3. Krown SE: Highly active antiretroviral therapy in AIDS-associated Kaposi's sarcoma: Implications for the design of therapeutic trials in patients with advanced, symptomatic Kaposi's sarcoma. J Clin Oncol 22:399-402, 2004[Free Full Text]

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Related Correspondence

• Highly Active Antiretroviral Therapy in AIDS-Associated Kaposi's Sarcoma (KS): Implications for the Design of Therapeutic Trials in Patients With Advanced Symptomatic KS
  Guglielmo Nasti and Umberto Tirelli
  JCO 2005 23: 2433 [Full Text]

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