{"id":21083,"date":"2020-03-10T12:00:00","date_gmt":"2020-03-10T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2020\/kaposi-sarcoma-aids-paclitaxel-clinical-trial"},"modified":"2024-11-03T15:16:49","modified_gmt":"2024-11-03T15:16:49","slug":"trial-should-change-care-for-aids-related-kaposi-sarcoma-in-sub-saharan-africa","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/trial-should-change-care-for-aids-related-kaposi-sarcoma-in-sub-saharan-africa\/","title":{"rendered":"Trial Should Change Care for AIDS-Related Kaposi Sarcoma in Sub-Saharan Africa"},"content":{"rendered":"

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Nurse Asekanadziwa Mthangwankia caring for a patient in the cancer ward at Kamuzu Central Hospital in\u00a0Lilongwe, Malawi.<\/p>\n

Credit: Image courtesy of UNC-Project Malawi Cancer Program<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

Results from a large clinical trial are expected to establish a new standard treatment for people with AIDS in sub-Saharan Africa who have advanced forms of Kaposi sarcoma. In the trial, treatment with the chemotherapy drug paclitaxel<\/a> greatly improved the outcomes of those with advanced AIDS-related Kaposi sarcoma<\/a> compared with the chemotherapy drugs typically used in these countries.<\/p>\n

From a public health perspective, the results are incredibly important, said the trial\u2019s lead investigator, Susan Krown, M.D., of the NCI-funded AIDS Malignancy Consortium (AMC). Kaposi sarcoma, which most often forms on the skin but in more severe cases can involve internal organs, is one of the most common cancers in many of the countries in sub-Saharan Africa, and it\u2019s most often diagnosed in those with AIDS.<\/p>\n

Dr. Krown noted that the limited health care infrastructures in many countries in sub-Saharan Africa make implementing changes in care a challenge. \u201cBut I think practice will move more toward the wider use of paclitaxel to treat AIDS-related Kaposi sarcoma based on these findings,\u201d she said.<\/p>\n

The results, published March 5 in The Lancet<\/em>, were unexpected, said Robert Yarchoan, M.D., director of NCI\u2019s Office of HIV and AIDS Malignancy<\/a>. When the trial was launched more than 7 years ago, there was little data on how the different treatments being used in the trial compared against one another.<\/p>\n

\u201cBut what they showed was that one, paclitaxel, was much better than the others,\u201d Dr. Yarchoan said.<\/p>\n

NCI and the National Institute of Allergy and Infectious Diseases<\/a> (NIAID) funded the trial. It was conducted in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, and South Africa) and Brazil, which also has high rates of AIDS-related Kaposi sarcoma.<\/p>\n

The findings come at a good time, with the improved availability and affordability of paclitaxel and other chemotherapy drugs in sub-Saharan Africa, said Satish Gopal, M.D., M.P.H., director of NCI\u2019s Center for Global Health<\/a>, who was not directly involved in the trial. Dr. Gopal previously lived and worked in Malawi as part of a longstanding research collaboration between the University of North Carolina and Malawi Ministry of Health, where for a time he was the only certified medical oncologist<\/a> in a country with a population of more than 18 million.<\/p>\n

These findings also provide much-needed scientific evidence to drive clinical decision-making, Dr. Gopal continued. Without such evidence, he explained, cancer treatment in sub-Saharan Africa is too often dictated\u00a0by drug availability and extrapolation of data from studies done in entirely different patient populations in high-income countries.<\/p>\n

With these new results, he said, \u201cclinicians and governments in the region can feel comfortable making informed treatment decisions, and developing practice guidelines and policies, that are grounded in a rigorously conducted study done in sub-Saharan Africa.\u201d\u00a0<\/p>\n

The Burden of AIDS-Related Kaposi Sarcoma<\/h2>\n

Tremendous progress has been made against HIV, both in preventing the infection and in treating AIDS, the disease it causes. This holds true for highly developed countries like the United States as well as in low- and middle-income countries around the globe.<\/p>\n

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The\u00a0A5263\/AMC-066 clinical trial enrolled\u00a0people with AIDS-related Kaposi sarcoma in 5 countries in sub-Saharan Africa (dark purple) and Brazil.<\/p>\n

Credit: National Cancer Institute<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

Nevertheless, in sub-Saharan Africa, AIDS-related malignancies like Kaposi sarcoma remain a significant health burden. In Uganda, for example, Kaposi sarcoma is the most common cancer in men and the second most common in women.\u00a0<\/p>\n

This is due to widespread presence in this region of Kaposi sarcoma-associated herpesvirus<\/a>, which causes Kaposi sarcoma, and HIV, which makes people particularly susceptible to developing this cancer, noted Dr. Gopal.<\/p>\n

While Kaposi sarcoma is very rare in the United States, in many sub-Saharan African countries \u201cit\u2019s truly a public health problem that\u2019s on the same order of magnitude of colorectal cancer or lung cancer in the United States,\u201d he said.<\/p>\n

Most countries in this region have limited and under-resourced health care systems that often cannot provide treatments that are readily available in the United States and other highly developed countries. For instance, in Malawi, access to radiation therapy<\/a>\u2014a mainstay treatment for many cancers\u2014is currently nonexistent.<\/p>\n

In people with AIDS-related Kaposi sarcoma, HIV-directed treatment\u2014known as antiretroviral therapy<\/a> (ART)\u2014can be effective as a stand-alone treatment in mild cases. But in more advanced cases, ART alone is insufficient and is often combined with chemotherapy, Dr. Yarchoan said. In sub-Saharan Africa, most patients are diagnosed with advanced disease.<\/p>\n

In the United States, either paclitaxel or liposomal doxorubicin<\/a> is usually combined with ART to treat advanced AIDS-related Kaposi sarcoma. But, in large part because of their expense, neither drug has been available in sub-Saharan Africa.\u00a0<\/p>\n

And despite the tremendous burden of AIDS-related Kaposi sarcoma there, little data were available on the efficacy of the chemotherapy regimens most commonly used to treat advanced AIDS-related Kaposi sarcoma, either etoposide alone or bleomycin used in combination with vincristine.<\/p>\n

According to Dr. Yarchoan, that knowledge gap created an opportunity that NIAID and NCI\u2014through their AIDS Clinical Trials Group and AMC, respectively\u2014felt they could address.<\/p>\n

A Much-Needed Trial\u00a0<\/h2>\n

From a broader scientific and clinical standpoint, Dr. Yarchoan stressed, there was a critical need for this clinical trial. No large trials of treatment for Kaposi sarcoma had been conducted in their entirety since ART was widely adopted more than 20 years ago. And it was the first large randomized trial<\/a> comparing chemotherapy regimens for the treatment of AIDS-related Kaposi sarcoma to be completed in more than a decade.<\/p>\n

The initial planning for the trial actually began in the mid-2000s, Dr. Krown said, and it had been\u00a0set to launch in 2011.<\/p>\n

But a shortage of liposomal doxorubicin at the time, which was supposed to be the drug that was compared against the two commonly used chemotherapy regimens, disrupted that plan. When it was clear that the shortage would not be resolved quickly, trial investigators shifted gears and took the steps needed to use paclitaxel instead. With that change, they were able to launch the trial in 2013.<\/p>\n

But conducting clinical trials in sub-Saharan Africa has its challenges, Dr. Krown explained, in part because medical staff there have limited experience with research studies. \u201cA lot of time was invested in training staff at the [trial] sites,\u201d she said. \u201cThere was a lot of training of clinicians, nurses, and pharmacists, and there was a lot of infrastructure building.\u201d<\/p>\n

More than 330 patients enrolled in the trial, with each randomly assigned to receive paclitaxel, etoposide, or bleomycin and vincristine, in addition to ART.\u00a0<\/p>\n

Participants treated with paclitaxel lived substantially longer without their disease getting worse (progression-free survival<\/a>) than those who received the other two treatments, particularly those treated with etoposide. At 48 weeks after beginning treatment, progression-free survival was 50% in the paclitaxel group compared with 20% in the etoposide group.<\/p>\n

In addition, patients who received paclitaxel were far more likely to experience reductions in the size of their tumors (tumor response<\/a>) than patients who received the other two chemotherapy regimens. The length of time those tumor responses lasted was also greater.<\/p>\n

Overall, patients treated with paclitaxel tolerated the drug well, Dr. Krown and her colleagues reported. For logistical reasons, paclitaxel was given less frequently than it is in the United States\u2014once every 3 weeks rather than once every 2 weeks.<\/p>\n

This lower \u201ctreatment intensity,\u201d however, didn\u2019t translate into less efficacy, they reported. The tumor response rates in this trial were the same as those seen in a large trial conducted in the United States that used a once-every-2-weeks treatment schedule<\/a>. It did, however, lead to much lower incidence of neutropenia<\/a>\u2014a drop in levels of white blood cells known as neutrophils, which increases the risk of infections\u2014than was seen with paclitaxel in the US trial.\u00a0<\/p>\n

The finding of a clear difference among these regimens \u201creally highlights the fact that we can learn things from trials in less-developed countries that can apply in the United States and throughout the world,\u201d Dr. Yarchoan said.<\/p>\n

And the liposomal doxorubicin shortage that slowed the launch of the trial appears to have had a silver lining, Dr. Krown said, since paclitaxel is now becoming more available in sub-Saharan Africa. \u201cAt the time, it didn\u2019t seem to be lucky, but things worked out well.\u201d<\/p>\n

From a Trial to Everyday Care<\/h2>\n

It\u2019s one thing to complete a clinical trial and publish the results. It\u2019s another altogether to see those results translated into everyday care. But a confluence of activities and initiatives should help in this regard, Dr. Yarchoan said.<\/p>\n