Stage-stratified treatment greatly reduces the need for chemotherapy in patients with early-stage HIV-related Kaposi's sarcoma (KS), leading to high overall survival rates in patients with early and advanced disease. These findings, from a study conducted in the United Kingdom, were published online on December 30 in the Journal of Clinical Oncology.
Mark Bower, PhD, FRCP, FRCPath, director of the National Centre for HIV Malignancies at Chelsea and Westminster Hospital in London, United Kingdom, and colleagues began using the stage-stratified approach to HIV-related KS treatment in 1998.
For their study, they assigned patients with early-stage (T0) KS to combined antiretroviral (cART) therapy alone, and those with advanced-stage (T1) KS to cART plus liposomal anthracycline chemotherapy. Of the 469 patients with HIV and KS, 303 had early-stage KS and 166 had advanced-stage KS.
Of the 237 patients with early-stage KS patients and no previous cART exposure, 213 (90%) of were treated with cART alone. Of the 66 patients being treated with cART when they were diagnosed with KS, 35 remained on the therapy; the remaining patients received additional treatment, including surgery, systemic chemotherapy, or radiotherapy, or were enrolled in a clinical trial. One patient declined treatment.
Of those with advanced-stage KS, 140 (84%) were treated with cART plus liposomal anthracycline chemotherapy, 14 (8%) were treated with cART alone, 9 (5%) were treated with cART and radiotherapy for localized ulcerating tumors, and 3 (2%) were treated with cART plus complete excision. Advanced-stage disease was defined by the presence of tumor-associated edema or ulceration, extensive oral or gastrointestinal KS, or other non-nodal visceral KS.
Five-year overall survival was 95% in the 213 cART-naïve early-stage KS patients treated with cART alone; 10-year survival was nearly as good, at 91%. Progression-free survival in this group was 77% at 5 years and 76% at 10 years.
First-line antiretroviral treatment included a protease inhibitor for 92 of the 303 patients with early-stage KS, and included a nonprotease inhibitor for 211. There was no significant difference in overall survival or progression-free survival between these 2 cART treatment regimens (log-rank P = .37).
Of the 140 patients with advanced KS treated with cART and liposomal anthracycline chemotherapy, the 5-year survival rate was 85% and the 10-year survival rate was 83%. Six of the 8 patients with advanced disease treated with cART alone required systemic chemotherapy within a year of KS diagnosis.
After initiating therapy, 58 patients (47 with early-stage KS) developed progressive KS, which was attributed to immune reconstitution inflammatory syndrome.
Study Validates This Approach
The staged-stratified treatment of KS is probably widely used, Dr. Bower explained, and is part of the British HIV Association malignancy guidelines. This study "validates this approach," he told Medscape Medical News in an email.
Treating early-stage KS without systemic chemotherapy eliminates the associated modest myelosuppression and "a theoretical risk for secondary malignancies, as well as cardiotoxicity (although that seems much less common than when nonliposomal formulations are used)," Dr. Bower said. "Furthermore, the chemotherapy will potentially lower CD4 rates."
Stage-stratified treatment for skin diseases in HIV patients has been adopted by the World Health Organization (WHO). This could have important consequences for the treatment of a variety of cancers in the developing world, according to Dr. Bowers and an accompanying editorial.
Similarly, "WHO guidelines that advocate the use of systemic chemotherapy could be the impetus to deliver safe intravenous chemotherapy, including the transport of drugs, the safe sterile reconstitution of drugs, the safe intravenous administration, and the appropriate aftercare and management of complications," Dr. Bowers told Medscape Medical News. "KS could act as a conduit for this progress. Rolling out chemo for advanced-stage KS...would necessitate the development of all this infrastructure for chemotherapy, which could be adopted for use in other cancers, such as breast cancer, or curable cancers, like lymphomas."
In their editorial, Jonathan Krell, MCRP, MBChB, associate faculty member, and Justin Stebbing, MD, PhD, MA, FRCP, professor of cancer medicine and oncology, both from the Imperial College of London, United Kingdom, write that the challenge now is to ensure that single-agent anthracyclines, particularly pegylated liposomal doxorubicin (PLD), can be delivered in the developing world, which would open the door for treatment with other chemotherapeutic agents.
"The delivery of PLD as a standard therapy for T1-stage KS will challenge budgets and distribution networks in many parts of the developing world, not only because of the cost of the drug itself, but also because of issues with the cost of sterile reconstitution and delivery in resource-poor settings. However, if PLD can be delivered as a therapy for KS in Africa and other developing countries, then one hopes that this may open the door for the more effective treatment of other curable cancers, such as testicular cancer and lymphoma, and common malignancies, such as early breast cancer or colon cancer, in which adjuvant chemotherapy would be recommended as standard of care in the developed world," they write.
The study authors and the editorialists have disclosed no relevant financial relationships.
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