UCLA-led research results in FDA approval of 4-drug combination for frontline treatment of metastatic pancreatic cancer

A four-drug chemotherapy regimen of irinotecan liposome (Onivyde) in combination with oxaliplatin, leucovorin, and fluorouracil—together referred to as NALIRIFOX—has been approved by the U.S. Food and Drug Administration (FDA) for the first-line treatment of metastatic pancreatic adenocarcinoma.

                                                                            Irinotecan

                                                                      Fluorouracil

                                                                    Folinic acid

                                                                Oxaliplatin

The FDA approval was based on results of the NAPOLI 3 trial, a study led by Dr. Zev Wainberg, co-director of the UCLA Health GI Oncology Program and a researcher at the UCLA Health Jonsson Comprehensive Cancer Center.

Findings from the NAPOLI 3 trial were first presented at the 2023 American Society of Clinical Oncology Gastrointestinal Cancers Symposium annual meeting and published in the Lancet in September of 2023. Wainberg, the global principal investigator for the trial, reported NALIRIFOX resulted in longer overall survival than a two-drug protocol comprised of nab-paclitaxel (Abraxane) and gemcitabine.

“The FDA approval is significant because of how difficult it is to treat metastatic pancreatic cancer,” said Wainberg, who is also a professor of medicine at the David Geffen School of Medicine at UCLA. “Metastatic pancreas cancer has long been recognized as a very difficult type of cancer to treat, but this study represents a possible new benchmark standard for current therapies and a promising avenue for ongoing research and drug development.”

The phase 3 study included 770 patients with pancreatic ductal adenocarcinoma, which makes up 95% of pancreatic cancers. Participants were from 250 sites in 25 countries and were randomly assigned to NALIRIFOX or the two-drug therapy.

Patients in the NALIRIFOX group had an overall survival of 11.1 months, compared with 9.2 months for those in the two-drug arm. Progression-free survival also increased with NALIRIFOX to 7.4 months versus 5.6 months with the two-drug regimen, which translates into a 30% reduction in the risk of disease progression or death.

The study is believed to be the first metastatic pancreatic cancer study in nearly a decade to have a positive endpoint for overall survival.

Most cases of pancreatic cancer are diagnosed at more advanced stages when the disease is more aggressive and has already started spreading to other parts of the body. There are also limited treatment options, which contributes to the high fatality rate of pancreatic cancer—Only about 13% of patients survive five or more years. In 2024 alone, the American Cancer Society estimates that around 35,000 people are anticipated to die from the disease.

The most common side effects people experienced in the trial included diarrhea, fatigue, nausea, vomiting, reduced appetite, abdominal pain, mucosal inflammation, constipation and decreased weight.

https://www.sciencedirect.com/science/article/pii/S0140673623013661?via%3Dihub

UCLA-led research results in FDA approval of 4-drug combination for frontline treatment of metastatic pancreatic cancer

Ipsen’s Onivyde Regimen, a Potential New Standard-of-Care First-Line Therapy in Metastatic Pancreatic Adenocarcinoma, Approved by FDA

Ipsen (Euronext: IPN; ADR: IPSEY) announced today that the U.S. Food and Drug Administration (FDA) has approved the supplemental new drug application for Onivyde (irinotecan liposome injection) plus oxaliplatin, fluorouracil and leucovorin (NALIRIFOX) as a first-line treatment in adults living with metastatic pancreatic adenocarcinoma (mPDAC). This is the second approval for an Onivyde regimen in mPDAC, following the FDA’s approval in 2015 of Onivyde plus fluorouracil and leucovorin following disease progression with gemcitabine-based therapy.

“The results from the Phase III NAPOLI 3 trial represent the first positive data for an investigational regimen in first-line metastatic pancreatic adenocarcinoma versus the currently approved nab-paclitaxel and gemcitabine regimen,” said Christelle Huguet, EVP and Head of Research and Development, Ipsen. “With today’s approval, this Onivyde (NALIRIFOX) regimen can now offer a potential new standard-of-care treatment option with proven survival benefits for people living with metastatic pancreatic adenocarcinoma in the U.S.”

Pancreatic adenocarcinoma (PDAC) is the most common type of cancer that forms in the pancreas, with more than 60,000 people diagnosed in the U.S. each year and nearly 500,000 people globally.3,4 Since there are no specific symptoms in the early stages, PDAC is often detected late and after the disease has spread to other parts of the body (metastatic or stage IV).5 Characterized as a complex cancer due to rapid tumor progression, limited genetic targets and multiple resistance mechanisms,6 mPDAC has a poor prognosis with fewer than 20% of people surviving longer than one year.4,5 Overall, pancreatic cancer has the lowest five-year survival rate of all cancer types globally and in the U.S.4,5

“Metastatic pancreatic adenocarcinoma is a difficult disease to manage with very few available treatment options. Given the reality of this aggressive form of cancer and the complexity of the disease, every advance in the treatment landscape represents a meaningful improvement in patient outcomes.” said Dr. Zev Wainberg, Professor of Medicine and Co-Director of the UCLA GI Oncology Program. “The approval of this Onivyde regimen is an important milestone for people living with mPDAC, their families and healthcare providers, with the NAPOLI 3 trial having demonstrated survival benefits versus a current standard of care treatment option.”

“We are pleased that the U.S. Food and Drug Administration has issued this new approval of the NALIRIFOX regimen. With each new approved treatment, there is more hope for those who will be diagnosed in the future and people currently living with pancreatic cancer may have more time with their loved ones,” said Julie Fleshman, JD, MBA, President and CEO of Pancreatic Cancer Action Network (PanCAN), a patient advocacy organization committed to providing evidence-based information and resources to patients and caregivers, along with advancing research to improve patient outcomes. “We are thankful to the patients who participated in this clinical trial as they play a crucial role in advancing treatments for pancreatic cancer.”

https://en.wikipedia.org/wiki/Irinotecan

Ipsen’s Onivyde Regimen, a Potential New Standard-of-Care First-Line Therapy in Metastatic Pancreatic Adenocarcinoma, Approved by FDA

Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study

In continuation of my updates on Erlotinib, gemcitabine and capecitabine

Additional treatments for locally advanced pancreatic cancer don't appear to boost survival, a new French study reports.

Researchers looked at the effects of adding a second drug -- erlotinib (Tarceva) -- to the initial round of chemotherapy. They also tested whether adding radiation to a second round of chemotherapy (chemoradiotherapy) would offer any survival benefit.

 erlotinib (Tarceva)

Unfortunately, the addition of the second drug didn't help people live longer, and those on chemoradiotherapy didn't fare any better.

"Chemoradiotherapy was not superior to chemotherapy," said the study's senior author, Dr. Pascal Hammel. Hammel is from the department of gastroenterology-pancreatology at Beaujon Hospital, in Clichy, France.

The study was funded by the pharmaceutical company Roche, the maker of Tarceva, and the French National Institute of Cancer.

More than 53,000 Americans are diagnosed with pancreatic cancer annually, the U.S. National Cancer Institute (NCI) says. About 42,000 Americans die each year from the disease, the NCI reports.

The new study focused on 449 people with pancreatic cancer. Their average age was just over 63.

All received standard four-month chemotherapy with the drug gemcitabine (Gemzar). Gemzar is currently used to treat a range of cancers, including pancreatic, ovarian, breast, and non-small cell lung cancers, the drug's labeling information says. For the study, about half the patients (219) also took Tarceva along with Gemzar.

 gemcitabine (Gemzar).

After completing initial treatment, imaging tests revealed that 269 patients appeared to have tumors that were under control. That meant their cancer was stable and didn't appear to have spread, or metastasized.

But the tumors couldn't be surgically removed because they had developed around the arteries surrounding the pancreas, study authors said.

About half this group of stable patients (136) received two additional months of the same chemotherapy regimen. The other half (133) was treated with a combination of radiation and the chemotherapy drug capecitabine (Xeloda).

 capecitabine (Xeloda)

After three years of follow-up, the researchers found that patients given Gemzar chemotherapy alone survived an average of 13.6 months. Those given the combination of Gemzar and Tarceva had an average survival of 11.9 months, the study found.

Patients treated with chemoradiotherapy lived an average of 15.2 months. Those who got chemotherapy alone lived an average of 16.5 months, the study found.

Hammel said there's still work to be done to improve the results of both chemotherapy and radiotherapy treatments.

But for now, Dr. Deborah Schrag agreed that "the French trial demonstrates that routine addition of chemo-radiation following initial chemotherapy for patients with locally advanced pancreatic cancer does not improve survival compared to continued chemotherapy." Schrag, chief of the Division of Population Sciences, Medical Oncology, at the Dana-Farber Cancer Institute in Boston, wrote an accompanying editorial in the same issue of the journal.

"[And] given the burdens of daily radiation therapy, there is no routine role for the application of this treatment strategy," added Schrag.

Schrag said it's possible there might be a certain group of pancreatic cancer patients who could get some measurable benefit from radiation. "Further evaluation of the tumor samples from the study participants might help to more precisely determine who might benefit from radiation, and such data are eagerly awaited," she said.

Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study  

Added benefit of crizotinib drug for first-line treatment of advanced bronchial carcinoma not proven

In continuation of my update on crizotinib

The drug crizotinib (trade name: Xalkori) has been available since 2012 for patients with advanced non-small cell lung cancer (bronchial carcinoma) who have a high activity of the enzyme anaplastic lymphoma kinase (ALK) and have already received another treatment. In November 2015, the approval was extended to first-line treatment.

After its assessment in 2013, the German Institute for Quality and Efficiency in Health Care (IQWiG) therefore now reassessed the added benefit of the drug in comparison with the appropriate comparator therapy - and found out: An added benefit of crizotinib for the first-line treatment of advanced bronchial carcinoma is not proven.

Carboplatin only in advanced risk of cisplatin side effects

Advanced bronchial carcinoma can only be treated palliatively. The Federal Joint Committee (G-BA) specified several appropriate comparator therapies for this. Either cisplatin in combination with a third-generation cytostatic agent was to be used in the control arm, or - in case of an increased risk of cisplatin side effects - carboplatin with a third-generation cytostatic agent. Monotherapy with gemcitabine or vinorelbine was an alternative option for patients with already severe limitations.

Use of carboplatin attached to condition

The drug manufacturer did not use the latter option and only submitted data from a randomized study in which crizotinib was directly compared with cisplatin or carboplatin, each in combination with the cytostatic agent pemetrexed. Carboplatin is not approved for the treatment of advanced non-small cell lung cancer, but can be prescribed in so-called off-label use. This is only the case for patients with an advanced risk of cisplatin side effects, e.g. in neuropathy, hearing impairment or susceptibility to nausea, renal insufficiency or cardiac failure.

The only submitted study did not fulfil the condition

Almost half of the participants received carboplatin in the control arm of the PROFILE 1014 study; the criteria for this individual medical decision were not comprehensible. A large proportion of the patients in the control arm did not correspond to the criteria of the Pharmaceutical Directive for the off-label use of carboplatin. Patients with neuropathy, renal insufficiency or cardiac failure were excluded from participation in the study and only about two and six per cent of the participants had notable hearing impairment or nausea as accompanying disease.

Hence the control group of the study did not adequately represent the appropriate comparator therapy. The data submitted were therefore unsuitable for the derivation of an added benefit of crizotinib in comparison with this comparator therapy.

Added benefit of crizotinib drug for first-line treatment of advanced bronchial carcinoma not proven: The drug crizotinib (trade name: Xalkori) has been available since 2012 for patients with advanced non-small cell lung cancer (bronchial carcinoma) who have a high activity of the enzyme anaplastic lymphoma kinase (ALK) and have already received another treatment. In November 2015, the approval was extended to first-line treatment.

Lenalidomide trials show potential for expanding lymphoma, leukaemia indications

Positive findings from two clinical trials have been published for the immunomodulatory agent lenalidomide in patients with heavily pretreated mantle cell lymphoma, and in adults with T-cell leukaemia-lymphoma or peripheral T-cell lymphoma.

The results of the phase II MCL-002 (SPRINT) study suggest that, compared with an investigator's choice of treatment, lenalidomide 25 mg/day on days 1-21 of a 28-day cycle significantly improved progression-free survival (PFS) in patients with relapsed or refractory mantle cell lymphoma who were ineligible for intensive chemotherapy or stem cell transplantation.

After a median of 15.9 months, the 170 lenalidomide-treated patients had a median PFS of 8.7 months compared with 5.2 months in the 84 patients who were treated with single-agent rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine, giving a hazard ratio (HR) of 0.61.

Lenalidomide trials show potential for expanding lymphoma, leukaemia indications

Adult cancer drugs show promise against an aggressive childhood brain tumor

Researchers relied on mice with group 3 medulloblastoma grown from patient tumors. The mice were developed in Roussel’s laboratory and are a powerful tool for testing the effectiveness of drugs against human tumors. Researchers used the mice to show that pemetrexed and gemcitabine worked against human group 3 tumors and that the drugs could be used in combination with existing chemotherapy agents to boost treatment effectiveness without undue risk. Cisplatin and cyclophosphamide were the other drugs used in this study.

“The finding provides a strong rationale for combination therapy with pemetrexed and gemcitabine for treatment of group 3 medulloblastoma,” Roussel said. Researchers found no evidence that mouse tumor cells develop resistance to the drugs.

Pemetrexed works by disrupting the ability of cancer cells to proliferate. Gemcitabine kills cells by triggering their suicide pathway. Researchers also found evidence the drugs work specifically against group 3 medulloblastoma. The drugs did not extend survival of mice with a different medulloblastoma subtype.

The study builds on previous St. Jude research that has helped to revolutionize understanding of the origins of medulloblastoma and laid the foundation for a new era of risk-based therapy. The goal is to maximize the likelihood of a cure and minimize long-term side effects. The approach combines clinical factors and the molecular markers associated with the different medulloblastoma subtypes to guide how radiation and chemotherapy are combined with surgery.

Adult cancer drugs show promise against an aggressive childhood brain tumor  

Two drugs in combination improve survival in patients with advanced pancreatic cancer

In continuation of my update on nab-paclitaxel (stands for nab-nanoparticle albumin-bound) and gemcitabine...

Investigators at the Vall d´Hebron University Hospital and the Vall d'Hebron Institute of Oncology (VHIO), have participated in an international phase III study, published in The New England Journal of Medicine. Results show that administering these two drugs in combination significantly improves one- and two-year survival in patients with advanced pancreatic cancer versus gemcitabine alone, the first-line treatment or most standard approach for this type of cancer to date.

The new drug is set to become a reference in advanced pancreatic cancer treatment. A multicentre phase III study, with centers participating from 11 countries in North America, Europe and Australia, shows that the drug combination nab-paclitaxel and gemcitabine is more effective in the treatment of patients with advanced pancreatic cancer than gemcitabine alone, which has been the standard treatment for these patients up until now.

The clinical trial, sponsored by Celgene Corporation, involved 861 patients, half of whom were administered the nab-paclitaxel/gemcitabine combination, while the other half received gemcitabine alone. Median overall survival was 8.5 months for nab-paclitaxel/gemcitabine versus 6.7 months for gemcitabine alone. One-year survival rates were 35% and 22%, respectively, and two-year survival rates were 9% and 4%, respectively. Similar side effects were found in the new drug and gemcitabine alike. The trial report therefore concluded that the nab-paclitaxel/gemcitabine combination significantly improves overall survival and response rate in patients with advanced pancreatic cancer.

Two drugs in combination improve survival in patients with advanced pancreatic cancer

Drug combination extends pancreatic cancer patient survival, study suggests

A multi-center Phase III clinical trial demonstrates that Abraxane (below left structure) (nab-paclitaxel) plus gemcitabine is the first combination of cancer drugs to extend survival of late-stage pancreatic cancer patients compared to standard treatment. Their findings show that Abraxane plus gemcitabine (below right structure) was well tolerated and resulted in clinically meaningful outcomes compared to gemcitabine alone, the current standard of care. 

MPACT is the largest phase III clinical trial completed in advanced pancreatic cancer with more than 800 patients. Findings from the study showed a 59 percent increase in one-year median survival rates from less than a quarter of the patients (22 percent) to more than a third (35 percent). The two-year survival rate for this cancer is negligible, less than 4 percent, but that more than doubles (9 percent) with the nab-paclitaxel/gemcitabine combination.

The study showed significant improvement among some of the sickest patients including those with increased metastases. Significantly there was no increase in life-threatening toxicity. Other drug combinations that have demonstrated benefit have been limited by increased toxicities.

"This is a major improvement in a cancer with the lowest survival rates among all cancer types," said Dr. Ramesh Ramanathan, medical director of Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare and principal investigator for the clinical trial in the United States. "Advanced pancreatic cancer is fourth most common cause of cancer death in the United States and throughout the world. It is difficult to diagnose with a majority of the cases diagnosed at a late stage after the disease has already advanced."

Drug combination extends pancreatic cancer patient survival, study suggests

Combination [of Vismodegib (GDC-0449) and Gemcitabine] therapy may help defeat pancreatic cancer

 In continuation of my update on (GDC-0449) Visodegib and Gemcitabine

GDC-0449 targets the Smoothened (SMO) protein in the Hedgehog signaling pathway. It was approved for use in basal cell carcinoma and is marketed as vismodegib. Kim and his colleagues felt that treating patients with pancreatic cancer first with GDC-0449 and then with the standard chemotherapeutic drug gemcitabine might disrupt the desmoplastic stroma and improve the efficacy of the chemotherapy. 

They evaluated this strategy in treatment-naive patients with advanced pancreatic cancer. Patients underwent needle biopsies of the cancer before and after taking GDC-0449 for three weeks to study the effects of GDC-0449 on the Hedgehog pathway signals, tumor stroma and pancreatic cancer stem cells. Gemcitabine was added to GDC-0449 following the second biopsy.

Combination therapy may help defeat pancreatic cancer

Cyclacel Presents New Phase 2 Data of Sapacitabine for MDS

We know that, Sapacitabine is an oral nucleoside analog prodrug that acts through a dual mechanism. The compound interferes with DNA synthesis by causing single-strand DNA breaks and induces arrest of the cell division cycle at G2 phase. Both sapacitabine and its major metabolite, CNDAC, have demonstrated potent anti-tumor activity in both blood and solid tumors in preclinical studies. In a liver metastatic mouse model, sapacitabine was shown to be superior to gemcitabine (Gemzar; Lilly) or 5-FU, two widely used nucleoside analogs, in delaying the onset and growth of liver metastasis.

Cyclacel has initiated a number of clinical trials to evaluate sapacitabine in both solid and hematological tumors laying the foundation for future Phase 2 studies and combination studies with other anti-cancer agents. Three Phase 1 studies have been completed, which evaluated safety and pharmacokinetics of a variety of dosing schedules in approximately 120 patients with solid tumors. Sapacitabine is currently being evaluated in two Phase 2 trials in patients with advanced cutaneous T-cell lymphoma (CTCL) and in elderly patients with acute myeloid leukemias (AML).

Now Cyclacel Pharmaceuticals, Inc. announced new data from an ongoing, multicenter, Phase 2 randomized trial of oral sapacitabine capsules in older patients with myelodysplastic syndromes (MDS) after treatment failure of front-line hypomethylating agents, such as azacitidine or decitabine.

Oncolytics REOLYSIN-Gemzar combination Phase 2 pancreatic cancer clinical trial meets primary endpoint

In continuation of my update on gemcitabine

Oncolytics REOLYSIN-Gemzar combination Phase 2 pancreatic cancer clinical trial meets primary endpoint: Oncolytics Biotech Inc. announced the interim data from a Phase 2 clinical trial using intravenous administration of REOLYSIN® in combination with gemcitabine (Gemzar) in patients with advanced pancreatic cancer (REO 017) indicated that the clinical study had successfully reached its primary endpoint, and that the drug combination is active.

ESPAC-3 trial (Fluorouracil and Folinic Acid) shows promising results to prevent pancreatic cancer

In continuation of my update on  drug discovery and 5-fluorouracil

A major international trial has shown a commonly used chemotherapy drug, 5-fluorouracil, and  Folinic Acid  is as effective at helping prevent pancreatic cancer returning after surgery as the more expensive standard chemotherapy treatment.

The results of the Cancer Research UK- funded study mean the cheaper drug - called 5-fluorouracil (5-FU) - could be prescribed in cases when the standard chemotherapy - gemcitabine - has failed, providing an extra lifeline for patients whose cancer comes back after surgery.

They also raise hopes that a new trial currently underway, looking at combining an oral version of 5-FU with the standard treatment of gemcitabine, could lead to a more effective treatment for pancreatic cancer patients who are eligible for surgery.

The trial, called European Study Group for Pancreatic Cancer (ESPAC)-3, is the largest of its kind and involved 159 centres in Europe, Australasia, Japan and Canada which between them recruited 1088 patients who had undergone surgery for pancreatic cancer.

One group had the standard chemotherapy treatment - gemcitabine. The second group had a cheaper widely available drug called 5-fluorouralcil (5-FU) that is commonly used in cancer treatment already.

The results mean that 5-FU should now also be considered one of the standard options for the treatment of patients with this disease.

They build on earlier trial results suggesting patients who had surgery and chemotherapy had better a chance of survival than patients who only had surgery. 

Finding out these two drugs are as effective as each other at preventing pancreatic cancer returning after surgery is important. It raises hopes that a new trial currently looking at giving two similar drugs together could be successful at preventing or at least delaying pancreatic cancer returning after surgery.

"Previous trial results involving advanced pancreatic cancer patients have shown this drug combination can give precious extra months or even years of life, so there is reason to be hopeful the survival benefit could be even more marked for patients who are eligible for surgery."

 Ref : http://jama.ama-assn.org/cgi/content/full/304/10/1073

Researchers Identify Two FDA Approved Drugs (Decitabine and Gemcitabine) That May Fight HIV....

Researchers at the University of Minnesota Academic Health Center have identified two drugs (Decitabine and Gemcitabine see structures)  that when combined, may serve as an effective treatment for HIV.

The researchers found that, two drugs, decitabine (left) and gemcitabine (below) (both FDA approved and currently used in pre-cancer and cancer therapy) were found to eliminate HIV infection in the mouse model by causing the virus to mutate itself to death an outcome researchers dubbed "lethal mutagenesis." Interestingly, this is for the first time that, this novel approach has been used to attack the deadly virus without causing toxic side effects. As the drugs are already approved for other purpose, it will be much easier to expedite the development of the drugs for human use.

"The findings provide hope that such an approach will someday help the 33 million people worldwide who currently live with HIV," Mansky said.

HIV mutates and evolves quickly. Rather than inhibiting virus growth and replication like current HIV drugs, this new drug combination forces the virus to do just the opposite evolve beyond control, to the point of extinction.

The lead researcher claims that HIV's ability to mutate makes it difficult to target and treat, and they wanted to take advantage of this behavior by stimulating HIV's mutation rate, essentially using the virus as a weapon against itself.

Researchers found that the drug concentrations needed to eliminate HIV infection cause no measureable cell toxicity and were effective against HIV cultures at concentrations well below the current levels used for cancer treatment.

Gemcitabine and decitabine have been administered in pre-clinical trials with mice. Initial findings confirm that the drugs are an effective antiviral therapy for HIV. And now the researchers are now in the process of modifying the drugs to forms that can be absorbed by the human body when taken orally.

Ref : http://jvi.asm.org/cgi/content/abstract/84/18/9301

Gemcitabine and cisplatin a promising combination for endometrial cancer...

In continuation of my update on cis-platin and its importance, I find this  info interesting to share with...

Gemcitabine (see structure) and cisplatin in combination have been investigated extensively in other disease sites, and synergism of the two agents has been confirmed in cell lines of human endometrial, ovarian, colon, lung and squamous cell head and neck carcinoma

Now researchers from The University of Texas M. D. Anderson Cancer Center , lead by Dr.Jubilee Brown, report from a small study of women with advanced or recurrent endometrial cancer, that gemcitabine and cisplatin, when used in combination, produced a response rate in fifty percent of patients.

The Phase II study of 20 patients found that the combination of gemcitabine and cisplatin, two drugs currently used to treat other types of cancer, limited the disease's progression, increasing progression-free survival while maintaining tolerable toxicity levels. It is believed that when administered together, gemcitabine helps overcome cell resistance to cisplatin, throwing tumor cells a potent one-two punch.


Findings demonstrated a 50 percent overall response rate, or improvement in disease. Additionally, the clinical benefit of the two-drug combination was 80 percent, as 16 of the 20 women experienced either an improvement or stabilization of disease. All side effects resulting from the therapy were manageable. Lead researcher, Dr. Brown concluded  that results from the study warrant investigation of the chemotherapy combination in a larger, definitive trial at multiple institutions.....

Ref :  Dr. Jubilee Brown, http://www.mdanderson.org/