Treating severe Kaposi’s sarcoma in South Africa is more likely to be successful when chemotherapy is used alongside antiretroviral therapy, researchers from the University of Kwazulu-Natal reported this week at the 17th Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco.
Kaposi’s sarcoma (KS) is a skin cancer that is considered to be an AIDS-defining illness. In Europe and North America the condition occurs largely in men who have sex with men, but in sub-Saharan Africa it is seen in all exposure categories.
The incidence of Kaposi’s sarcoma has been rising in recent years as the number of severely immunosuppressed people grows in sub-Saharan Africa, and in Kwazulu-Natal the incidence is estimated at 30 cases per 100,000 inhabitants per year.
Although milder cases of Kaposi’s sarcoma often fade away after antiretroviral therapy is begun, more severe disseminated cases that affect the internal organs such as the lungs, or which are widespread over the body, may not resolve as immune status improves, and the prognosis of people with advanced Kaposi’s sarcoma is relatively poor.
Researchers at the University of Kwazulu-Natal designed a study to determine whether chemotherapy provided alongside antiretroviral therapy would be safe and effective.
The KAART study was an open-label, randomised controlled trial. All the patients were starting HIV treatment for the first time and had biopsy-proven Kaposi’s sarcoma.
A total of 59 patients were randomised to receive antiretroviral therapy alone (3TC, d4T and nevirapine in the combined pill Triomune). A further 53 patients were randomised to receive both Triomune plus anti-KS chemotherapy consisting of bleomycin, doxorubicin, and vincristine (the ABV regimen). This regimen was chosen because it is the most commonly available in southern Africa.
Response rates were evaluated according to established prognostic factors. Using an intent-to-treat analysis, the investigators compared clinical response rate between the two arms after twelve months of treatment. They also compared overall survival and quality of life.
Most of the patients had poor prognostic factors. KS was staged as T1 (poor risk) in 89% of individuals, 58% had a CD4 cell count below 200 cells/mm3 and 42% had another serious illness, tuberculosis being the most common (34%).
The twelve-month overall response rate was significantly better in the patients who received chemotherapy in addition to antiretroviral therapy (66% vs 39%, p = 0.005). The response rate was also significantly faster in this group of patients (p < 0.001).
However, overall twelve-month survival was comparable between the two arms of the study at 76%.
Adherence, CD4 cell count increases, fall in viral load and the frequency of side-effects were comparable between the two groups of patients.
The most important factor associated with overall response was KS disease staging and the presence of systemic disease (opportunistic infections such as tuberculosis) (p = 0.03).
Quality of life information was available for 111 patients. This improved significantly from a score of 50 at baseline to 67 after one year of treatment (p < 0.001). Improvements were observed in emotional wellbeing, cognitive ability, social functioning, and most symptoms. There was no difference in quality of life changes between the two arms of the study, but there was a strong, though non-significant, trend towards greater improvement in pain in the chemotherapy group.
Presenting the findings Dr Anisa Mosam of the University of Kwazulu-Natal said: “Early addition of chemotherapy plays an important palliative role in patients with Kaposi’s sarcoma in sub-Saharan Africa.
Further information from aidsmap.com
A detailed clinical review of the management of Kaposi’s sarcoma in resource-limited settings was published in HIV & AIDS Treatment in Practice in February 2008.
Further information from CROI
Mosam A et al. The KAART trial: a randomised controlled trial of HAART compared to the combination of HAART and chemotherapy in treatment naïve patients with HIV-associated Kaposi’s sarcoma in KwaZulu Matal, South Africa, NCT 00380770. Seventeenth Conference on Retroviruses and Opportunistic Infections, abstract 32, San Francisco, 2010.