Gene Transfer Therapy Destroys Tumors in Chronic Lymphocytic Leukemia Patients; Holds Promise For Ovarian Cancer

Penn researchers have shown sustained remissions of up to a year among a small group of advanced chronic lymphocytic leukemia (CLL) patients treated with genetically engineered versions of their own T-cells. This genetically-modified “serial killer” T-cell approach could provide a tumor-attack roadmap for the treatment of  ovarian, lung, and pancreatic cancer, as well as myeloma and melanoma.

In a cancer treatment breakthrough 20 years in the making, researchers from the University of Pennsylvania’s Abramson Cancer Center and Perelman School of Medicine have shown sustained remissions of up to a year among a small group of advanced chronic lymphocytic leukemia (CLL) patients treated with genetically engineered versions of their own T-cells.

The protocol involves removing patients’ cells and modifying them in Penn’s vaccine production facility, followed by the infusion of the new cells back into the patient’s body following chemotherapy. This approach also represents a potential tumor-attack roadmap for the treatment of other cancers including those of the lung and ovaries and myeloma and melanoma. The findings, published simultaneously yesterday in the New England Journal of Medicine (NEJM) and Science Translational Medicine, are the first demonstration of the use of gene transfer therapy to create “serial killer” T-cells aimed at cancerous tumors.

Carl June, M.D., Ph.D., Principal Investigator; Director, Translational Research & Professor of Pathology & Laboratory Medicine, Abramson Cancer Center, University of Pennsylvania

David Porter, M.D., Co-Principal Investigator; Director, Blood & Marrow Transplantation & Professor of Medicine, Abramson Cancer Center, University of Pennsylvania

“Within three weeks, the tumors had been blown away, in a way that was much more violent than we ever expected,” said senior author Carl June, M.D., Ph.D., director of Translational Research and a professor of Pathology and Laboratory Medicine in the Abramson Cancer Center, who led the work. “It worked much better than we thought it would.”

The results of the pilot trial of three patients are a stark contrast to existing therapies for CLL. The patients involved in the new study had few treatment options. The only potential curative therapy would have involved a bone marrow transplant, a procedure which requires a lengthy hospitalization and carries at least a 20 percent mortality risk — and even then offers only about a 50 percent chance of a cure, at best.

“Most of what I do is treat patients with no other options, with a very, very risky therapy with the intent to cure them,” says co-principal investigator David Porter, M.D., Professor of Medicine and Director of Blood and Marrow Transplantation. “This approach has the potential to do the same thing, but in a safer manner.”

Secret Ingredients

Dr. June thinks there were several “secret ingredients” that made the difference between the lackluster results that have been seen in previous trials with modified T cells and the remarkable responses seen in the current trial. The details of the new cancer immunotherapy are detailed in Science Translational Medicine.

After removing the patients’ cells, the team reprogrammed them to attack tumor cells by genetically modifying them using a lentivirus vector. The vector encodes an antibody-like protein, called a chimeric antigen receptor (CAR), which is expressed on the surface of the T-cells and designed to bind to a protein called CD19 (Cluster of Differentiation 19).

Once the T-cells start expressing the CAR, they focus all of their killing activity on cells that express CD19, which includes CLL tumor cells and normal B-cells. All of the other cells in the patient that do not express CD19 are ignored by the modified T-cells, which limits side effects typically experienced during standard therapies.

The team engineered a signaling molecule into the part of the CAR that resides inside the cell. When it binds to CD19, initiating the cancer cell death, it also tells the cell to produce cytokines that trigger other T-cells to multiply — building a bigger and bigger army until all of the target cells in the tumor are destroyed.

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Serial Killers

“We saw at least a 1000-fold increase in the number of modified T-cells in each of the patients. Drugs don’t do that,” June says. “In addition to an extensive capacity for self-replication, the infused T-cells are serial killers. On average, each infused T-cell led to the killing of thousands of tumor cells – and overall, destroyed at least two pounds of tumor in each patient.”

The importance of the T-cell self-replication is illustrated in the New England Journal of Medicine paper, which describes the response of one patient, a 64-year old man. Prior to his T-cell treatment, his blood and marrow were replete with tumor cells. For the first two weeks after treatment, nothing seemed to change. Then on day 14, the patient began experiencing chills, nausea, and increasing fever, among other symptoms. Tests during that time showed an enormous increase in the number of T-cells in his blood that led to tumor lysis syndrome, which occurs when a large number of cancer cells die all at once.

By day 28, the patient had recovered from the tumor lysis syndrome –– and his blood and marrow showed no evidence of leukemia.

“This massive killing of tumor is a direct proof of principle of the concept,” Porter says.

The Penn team pioneered the use of the HIV-derived vector in a clinical trial in 2003 in which they treated HIV patients with an antisense version of the virus. That trial demonstrated the safety of the lentiviral vector used in the present work.

The cell culture methods used in this trial reawaken T-cells that have been suppressed by the leukemia and stimulate the generation of so-called “memory” T-cells, which the team hopes will provide ongoing protection against recurrence. Although long-term viability of the treatment is unknown, the doctors have found evidence that months after infusion, the new cells had multiplied and were capable of continuing their “seek-and-destroy” mission against cancerous cells throughout the patients’ bodies.

Moving forward, the team plans to test the same CD19 CAR construct in patients with other types of CD19-positive tumors, including non-Hodgkin’s lymphoma and acute lymphocytic leukemia. They also plan to study the approach in pediatric leukemia patients who have failed standard therapy. Additionally, the team has engineered a CAR vector that binds to mesothelin, a protein expressed on the surface of mesothelioma cancer cells, as well as on ovarian and pancreatic cancer cells.

In addition to June and Porter, co-authors on the NEJM paper include Bruce Levine, Ph.D., Michael Kalos, Ph.D., and Adam Bagg MB, BCh, all from Penn Medicine. Michael Kalos and Bruce Levine are co-first authors on the Science Translational Medicine paper. Other co-authors include Carl June, M.D., Ph.D., David Porter, M.D., Sharyn Katz, M.D., MTR, and Adam Bagg MB, BCh, from Penn Medicine, and Stephan Grupp, M.D., Ph.D., from the Children’s Hospital of Philadelphia.

The work was supported by the Alliance for Cancer Gene Therapy, a foundation started by Penn graduates Barbara and Edward Netter, to promote gene therapy research to treat cancer, and the Leukemia & Lymphoma Society.

Accompanying NEJM Editorial

In an accompanying NEJM editorial, Walter J. Urba, M.D., Ph.D. and Dan L. Longo, M.D. raise several important consideration in regard to the genetically-modified, serial killer T-cell therapy discussed above.

First, the editorial authors note that chimeric antigen receptors (or CARS) have theoretical advantages over other T-cell–based therapies, including: (i) use of the patient’s own cells, which avoids the risk of graft-versus-host disease; (ii) the ability to create CARs quickly; and (iii) use of the same CAR for multiple patients.

While noting the remarkable clinical outcome of the 64-year old male CLL patient described above, the editorial authors note that in addition to tumor lysis syndrome, the patient experienced B-cell depletion and hypogammaglobulinemia. Although these conditions may not create a major problem in patients with CLL, the authors state that the persistence of activated T-cells, memory T-cells, or both could pose substantial problems in other tumor types.

According to the editorial authors, both toxic effects to the target organ and also “on-target, but off-organ” toxic effects have been observed by other researchers in the past because of unanticipated cross-reactive target antigens.

While toxicity may become more of a problem as more potent second- and third-generation CARs are used in patients with different tumor types, the authors explain that additional safety measure may help offset that risk. The safety measures highlighted in the editorial include: (i) the infusion of a lower number of T-cells, (ii) the use of immunosuppressive agents, and (iii) the introduction of an inducible “suicide signal” to kill the cells when they are creating mischief.

In connection with the third safety measured provided above, the authors state that a novel, non-immunogenic, inducible caspase 9suicide gene” has already been developed. Nevertheless, the authors warn that the suicide gene strategy may not have time to work properly because the deaths from toxic effects reported in the past have been severe and occurred within hours after administration of the gene-transfected cells.

The editorial authors conclude that only with the more widespread clinical use of CAR T-cells will researchers learn whether the results reported by Porter et al. represent a true advancement toward a clinically applicable and effective therapy, or alternatively, another promising strategy that runs into an insurmountable barrier which is difficult to overcome.

About Penn Medicine

Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $4 billion enterprise.

About the University of Pennsylvania Perelman School of Medicine

Penn’s Perelman School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools and among the top 10 schools for primary care. The school is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $507.6 million awarded in the 2010 fiscal year.

About the University of Pennsylvania Health System

The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania — recognized as one of the nation’s top 10 hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital – the nation’s first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2010, Penn Medicine provided $788 million to benefit our community.


  • Urba WJ & Longo DL. Redirecting T CellsN Engl J Med Editorial. Published online August 10, 2011 (10.1056/NEJMe1106965).

ASCO 2011: Novel Multi-targeted Agent Cabozantinib (XL184) Has Significant Effect on Several Advanced Solid Tumors

Cabozantinib (XL184) demonstrated high rates of disease control in patients with prostate, ovarian and liver cancers. The investigators concluded that cabozantinib exhibits clinical activity in ovarian cancer patients with advanced disease, regardless of prior platinum drug status, as reflected by the high rates of response. 

ASCO Releases Studies From Upcoming Annual Meeting – Important Advances in Targeted Therapies, Screening, and Personalized Medicine

The American Society of Clinical Oncology (ASCO) today highlighted several studies in a press briefing from among more than 4,000 abstracts publicly posted online at in advance of ASCO’s 47th Annual Meeting. An additional 17 plenary, late-breaking and other major studies will be released in on-site press conferences at the Annual Meeting.

The meeting, which is expected to draw approximately 30,000 cancer specialists, will be held June 3-7, 2011, at McCormick Place in Chicago, Illinois. The theme of this year’s meeting is “Patients. Pathways. Progress.”

“This year marks the 40th anniversary of the signing of the National Cancer Act, a law that led to major new investments in cancer research. Every day in our offices, and every year at the ASCO meeting, we see the results of those investments. People with cancer are living longer, with a better quality of life, than ever before,” said George W. Sledge Jr., M.D., President of ASCO, Ballve-Lantero Professor of Oncology and professor of pathology and laboratory medicine at the Indiana University School of Medicine.

“With our growing understanding of the nature of cancer development and behavior, cancer is becoming a chronic disease that a growing number of patients can live with for many years,” said Dr. Sledge. “The studies released today are the latest examples of progress against the disease, from new personalized treatments, to new approaches to screening and prevention.”

The study results from a phase II clinical trial involving cabozantinib (XL184) were highlighted today in the ASCO press briefing, as summarized below.

Novel Multi-targeted Agent Cabozantinib (XL184) Has Significant Effect on Several Advanced Solid Tumors, and Can Shrink or Eliminate Bone Metastases 

Cabozantinib (XL184) – an oral inhibitor of MET and VEGFR2 kinases involved in the development and progression of many cancers – showed strong responses in patients with various advanced cancers in a phase II trial. The drug demonstrated particularly high rates of disease control for advanced prostate, ovarian and liver cancers, which are historically resistant to available therapies. The drug also fully or partially eliminated bone metastases in patients with breast and prostate cancers and melanoma.

Michael S. Gordon, M.D., President & Chief Executive Officer, Pinnacle Oncology Hematology.

“Cabozantinib appears to have significant effects on several treatment-resistant tumors, as well as impressive effects on bone metastases. In addition, these effects are associated with rapid improvement in pain, a reduction in opiate narcotic requirements and improvement in anemia,” said lead author Michael S. Gordon, M.D., a medical oncologist at Pinnacle Oncology Hematology located in Scottsdale, Arizona. “The implications of these results are very exciting—it is unusual to find a targeted therapy, absent of a molecular mutation in tumors, that works in bony disease and has this activity.”

To be eligible for the study, patients had to have advanced, progressive solid tumors, with or without bone metastases. Of 398 evaluable patients (of 483 enrolled in the trial), 39 percent had bone metastases at baseline. Patients received cabozantinib over 12 weeks. The trial was designed as a “discontinuation” trial, in which those who had partial responses stayed on the drug; those with stable disease were randomized to cabozantinib or placebo; and patients with progressive disease were removed from the trial. This novel type of clinical trial design more quickly evaluates the disease-stabilizing activity of growth-inhibitory agents like cabozantinib, compared to the traditional model of randomizing all patients to either the experimental arm or placebo.

Among 398 patients evaluable with all types of cancer included in the trial, the collective overall response rate was 9 percent (34 of 398). The highest disease control rates (partial response and stable disease) at week 12 were 76 percent for liver cancer (22 of 29 patients), 71 percent for prostate cancer (71 of 100 patients), and 58 percent for ovarian cancer (32 of 51 patients). [emphasis added].

Of the 51 evaluable ovarian cancer patients noted above, 28 are platinum drug resistant, 17 are platinum drug sensitive, and 6 have unknown status. The median number of systemic treatments prior to trial enrollment was 2. The overall response rate (complete response and partial response based on modified RECIST criteria) for ovarian cancer was 12/51 (24%).  Upon breakdown, the response rate was 5/28 (18%) for platinum drug resistant patients, and 5/17 (29%) for platinum drug sensitive patients. Five additional partial responses await confirmation. After a median follow-up of 4 months (range: 1 to 11 months), the median duration of response and median progression free survival have not been reached. The most common related adverse events ( ≥grade 3) among ovarian cancer patients were hand-foot syndrome (10%), diarrhea (8%) and fatigue (4%). Drug dose reductions and permanent discontinuations for adverse events occurred in 43% and 10% of the ovarian cancer patients, respectively. Based on these findings, the investigators concluded that cabozantinib exhibits clinical activity in ovarian cancer patients with advanced disease, regardless of prior platinum drug status, as reflected by the high rates of response. [emphasis added] Accordingly, randomization in the ovarian cancer cohort was halted & patients unblinded due to the observed high efficacy.

Fifty-nine of 68 patients with bone metastases (including patients with breast and prostate cancers and melanoma) experienced either partial or complete disappearance of the cancer on bone scans, often with significant pain relief and other improved cancer-related symptoms.

The reduction of bone metastases and pain relief was an unexpected finding in this study, Dr. Gordon said. Independent review by radiologists confirmed that bone metastases disappeared in the majority of patients who had bone metastases when they entered the study. The majority of these patients had castration-resistant prostate cancer (CRPC), but patients with breast cancer and melanoma also had disappearance of bone metastases. Bone metastases greatly contribute to morbidity and mortality in patients with these types of cancer, which typically spread to the bone.

Due to these results, the study has been expanded to include more CRPC patients. Similarly, the high rate of lasting responses in ovarian cancer patients led researchers to also expand the study to evaluate the drug’s effect on patients with a particularly resistant form of the disease known as platinum drug resistant/refractory ovarian cancer. [emphasis added]

This study expansion results will help determine the design of future phase III trials, which will assess whether the drug extends patients lives or has other longer-term benefits among patients with specific cancer types. At present, cabozantinib is being investigated for use as a single agent. Additional studies will evaluate the efficacy and tolerability of appropriate combinations with other agents for future indications.

For the solid tumor patients collectively, the most common grade three or above adverse events were fatigue (9 percent) and hand-foot syndrome (8 percent). Dose reductions were required in 41 percent of patients due to side effects; 12 percent were removed from the trial for adverse events.



Cabozantinib (XL184) Clinical Trials:

Related Libby’s H*O*P*E*™ Postings:

Novel Cancer-Targeting “Cornell Dot” Nanoparticle Approved for First-In-Human Clinical Trial

“Cornell Dots” — brightly glowing nanoparticles — may soon be used to light up cancer cells to aid in diagnosing and treating cancer. The U.S. Food and Drug Administration (FDA) has approved the first clinical trial in humans of the new technology. It is the first time the FDA has approved using an inorganic material in the same fashion as a drug in humans.

“Cornell Dots” (or “C dots”) — brightly glowing nanoparticles — may soon be used to light up cancer cells to aid in diagnosing and treating cancer. The U.S. Food and Drug Administration (FDA) has approved the first clinical trial in humans of the new technology. It is the first time the FDA has approved using an inorganic material in the same fashion as a drug in humans.

Michelle Bradbury, M.D., Ph.D., Clinician-Scientist, Neuroradiology Service, Memorial Sloan-Kettering Cancer Center; Assistant Professor, Radiology, Weill Cornell Medical College; Lead Study Investigator

Researchers at Memorial Sloan-Kettering Cancer Center’s Nanotechnology Center, along with collaborators at Cornell University and Hybrid Silica Technologies, have received approval for their first Investigational New Drug Application (IND) from the FDA for an ultrasmall silica inorganic nanoparticle platform for targeted molecular imaging of cancer, which may be useful for cancer treatment in the future. Center researchers are about to launch their first-in-human clinical trial in melanoma patients using this first-of-its-kind inorganic nanoparticle to be approved as a drug. “This is a very exciting and important first step for this new particle technology that we hope will ultimately lead to significant improvements in patient outcomes and prognoses for a number of different cancers,” said Michelle Bradbury, M.D., Ph.D., a clinician-scientist on Memorial Sloan-Kettering’s Neuroradiology Service and an assistant professor of radiology at Weill Cornell Medical College, who is the lead investigator of the study, along with Snehal Patel, M.D., a surgeon on Memorial Sloan-Kettering’s Head and Neck Service, who is a co-principal investigator.

“This is a very exciting and important first step for this new particle technology that we hope will ultimately lead to significant improvements in patient outcomes and prognoses for a number of different cancers.”

— Michelle Bradbury, M.D., Ph.D., lead investigator of the study and clinician-scientist on Memorial Sloan-Kettering’s Neuroradiology Service and an assistant professor of radiology at Weill Cornell Medical College

C dots were initially developed as optical probes at Cornell University, Ithaca, by Ulrich Wiesner, Ph.D., a professor of materials science and engineering who, along with Hybrid Silica Technologies, the supplier of C dots, has spent the past eight years precisely engineering these particles. C dots are silica spheres less than 8 nanometers in diameter that enclose several dye molecules. (A nanometer is one-billionth of a meter, about the length of three atoms in a row.) The silica shell, essentially glass, is chemically inert and small enough to pass through the body and out in the urine. For clinical applications, the dots are coated with polyethylene glycol so the body will not recognize them as foreign substances.

C dots were subsequently modified at Memorial Sloan-Kettering for use in PET (positron emission tomography) imaging. C dots are tiny silica spheres that contain dye that glows three times more brightly than simple free dyes when excited by light of a specific wavelength. C dots can “light up” cancer cells, and act as tumor tracers for tracking the movement of cells and assisting in the optical diagnosis of tumors near the skin surface. The attachment of a radioactive label produces a new generation of multimodal (PET-optical) particle probes that additionally enable deeper detection, imaging, and monitoring of drug delivery using three-dimensional PET techniques.

Ulrich Wiesner, Ph.D. (left), a Cornell University Professor of Materials Science & Engineering, works with graduate students Jennifer Drewes & Kai Ma to characterize the size & brightness of C dots in their Bard Hall lab. (Photo: Jason Koski/University Photography)

C dots can be tailored to any particle size. Previous imaging experiments in mice conducted by the Memorial Sloan-Kettering team showed that particles of a very small size (in the 5 to 7 nanometer range) could be retained in the bloodstream and efficiently cleared through the kidneys after applying a neutral surface coat. More recently, the research team molecularly customized C dots to create a new particle platform, or probe, that can target surface receptors or other molecules expressed on tumor surfaces and that can be cleared through the kidneys.

Using PET scans, C dots can be imaged to evaluate various biological properties of the tumors, including tumor accumulation, spread of metastatic disease to lymph nodes and distant organs, and treatment response to therapy. The information gained from imaging tumors targeted with this multimodal platform may also assist physicians in defining tumor borders for surgery, and improving real-time visualization of small vascular beds, anatomic channels, and neural structures during surgery.

The purpose of this trial is to evaluate the distribution, tissue, uptake, and safety of the particles in humans by PET imaging. This study will provide data that will serve as a baseline to guide the design of future surgical and oncologic applications in the clinic. “The use of PET imaging is an ideal imaging technology for sensitively monitoring very small doses of this new particle probe in first-in-human trials,” added Steven Larson, M.D., Chief of Memorial Sloan-Kettering’s Nuclear Medicine Service.

Memorial Sloan-Kettering nanochemist Oula Penate Medina, Ph.D., notes that “this is an important trial in that it will help to answer a number of key questions regarding future potential applications of this multimodal system. Once the door has been opened, new and emerging fields, such as targeted drug delivery, can be investigated. We expect that these particles can be adapted for multiple clinical uses, including the early diagnosis and treatment of various cancers, as well as for sensing changes in the microenvironment.”

“This clinical trial is the culmination of a longstanding collaborative effort with our colleagues at Cornell and Hybrid Silica Technologies, as well as a testament to our own institutional colleagues here at the Center,” Dr. Bradbury said. “With the support of many, in particular the Office of Clinical Research, we’ve pushed to translate the C dots from a laboratory idea to our first FDA IND-approved inorganic nanomedicine drug product to be tested in the clinic,” Dr. Bradbury said.

The work was funded in part by the Clinical and Translational Science Center, Weill Cornell Medical College, the Cornell Nanobiology Center, and the National Institutes of Health (NIH) Small-Animal Imaging Research Program (SAIRP). In addition to Drs. Bradbury, Penante-Medina, Larson, Patel, and Wiesner, the following Memorial Sloan-Kettering investigators contributed to and/or supported this work: Pat Zanzonico, Ph.D.; Heiko Schöder, M.D.; Elisa De Stanchina, Ph.D.; Hedvig Hricak, M.D., Ph.D., Chair of the Department of Radiology; as well as Hooisweng Ow, Ph.D., of Hybrid Silica Technologies, Inc.; Memorial Sloan-Kettering’s Office of Clinical Research; and the Cyclotron Core.


National Comprehensive Cancer Network® Posts New Guidelines for Treatment of Ovarian Cancer Patients

National Comprehensive Cancer Network® Posts New “Patient Friendly” Guidelines for Treatment of Ovarian Cancer.

Women with ovarian cancer now have a new resource that provides them with the same credible information their physicians use when determining treatment options. The National Comprehensive Cancer Network® (NCCN®) announces three new additions to the library of NCCN Guidelines for Patients™, patient-friendly translations of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™). NCCN Guidelines for Patients™: Melanoma, Ovarian Cancer, and Prostate Cancer are now available free of charge at

The NCCN Guidelines for Patients™ are designed to provide people with cancer and their caregivers with state-of-the-art treatment information in easy-to-understand language. Given the prevalence of melanoma and prostate cancer – both among the most frequently diagnosed cancers in men – and the challenges in detecting ovarian cancer in women, it is critical that patients have resources to empower them to take a more active role in their treatment.

The NCCN Guidelines™ are developed by multidisciplinary panels of experts from NCCN Member Institutions and feature algorithms or “decision trees” that address every appropriate treatment option from initial work up throughout the course of the disease. The NCCN Guidelines for Patients™ translate these professional guidelines in a clear, step-by-step manner that patients can use as the basis for making decisions and discussing options with their physicians.

The NCCN Guidelines for Patients™ are available free of charge at, which also features additional informative articles for patients and caregivers.

About the National Comprehensive Cancer Network

The National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives.

The NCCN Member Institutions are:

City of Hope Comprehensive Cancer Center, Los Angeles, CA;

Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA;

Duke Comprehensive Cancer Center, Durham, NC;

Fox Chase Cancer Center, Philadelphia, PA;

Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT;

Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA;

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD;

Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL;

Memorial Sloan-Kettering Cancer Center, New York, NY;

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL;

The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, Columbus, OH;

Roswell Park Cancer Institute, Buffalo, NY;

Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO;

St. Jude Children’s Research Hospital/University of Tennessee Cancer Institute, Memphis, TN;

Stanford Comprehensive Cancer Center, Stanford, CA;

University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL;

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA;

University of Michigan Comprehensive Cancer Center, Ann Arbor, MI;

UNMC Eppley Cancer Center at The Nebraska Medical Center, Omaha, NE;

The University of Texas MD Anderson Cancer Center, Houston, TX; and

Vanderbilt-Ingram Cancer Center, Nashville, TN.


Vox Populi*: Libby, We’ll Be Missing You

Vox Populi:  Libby, We’ll Be Missing You.

voxpopDear Libby,

One year ago today, you left us after an extended battle with ovarian cancer.  You are missed as a wife, a daughter, a sister, an aunt and a cousin.  You were, and continue to be, a very special family member to your loved ones who remain behind.  You battled this insidious disease with courage but lost that battle in the prime of your life at age 26.

I wonder why your life was cut short by this disease.

I wonder why an effective screening test has not been discovered by a country that set a lofty goal of landing a man on the moon and accomplished that goal within a decade.

I wonder why there are so many pink ribbons yet so few teal ribbons.

I wonder how the mothers of a major Hollywood celebrity (Angelina Jolie) and the President of the U.S. (Barack Obama) could die from ovarian cancer, yet U.S. women remain generally unaware of the early warning signs and symptoms of the disease.

I have faith that you are in a much better place now.  A place that only knows pure love.  A place that knows no pain or suffering. A place where there are logical answers to my questions above.

I remember when you rode in my new red convertible sports car at the age of 11 with your blond hair blowing behind you in the wind.  At that moment, your life seemed limitless.

I remember when, as a young adult, you helped others who could not help themselves.  You chose generosity and kindness while many of your peers sought money and power.

I remember your positive attitude after initial diagnosis, despite the fact that you had every reason to blame life and others for your plight.

I remember your dry sense of humor after a doctor attempted to soften the blow of a disease recurrence diagnosis by telling you that even he could step out into the street tomorrow and get hit by a bus.  You suggested that the doctor needed serious help with his “people skills,” but joked that his insensitive statement should appear on an ovarian cancer fundraising T-shirt.

I remember how you continued to seek out medical solutions to your disease in the face of dire odds and statistics.

I remember “hearing” your smile on the telephone, regardless of our 3,000 mile separation.

I will always remember your example of love, faith, hope, courage, persistence, and ultimately, acceptance.

On July 28, 2008, I wrote about two songs that immediately came to mind after I heard about your passing.  One year later, two songs again come to mind based upon your inspiration and memory.

The first song is I’ll Be Missing You.

I’ll Be Missing You was written by Terry “Sauce Money” Carroll and performed by Sean “Diddy” Combs (then Puff Daddy), Faith Evans and 112.  Terry Carroll received a 1997 Grammy Award for the song that is based in part upon the melody of the 1983 Grammy Award-Winning song Every Breath You Take (written by Sting and performed by The Police).  I’ll Be Missing You was inspired by the memory of Combs’ fellow Bad Boy Records artist Christopher Wallace (aka Notorious B.I.G. ) who died in March 1997.  The song lyrics express what our family is feeling today when we think of you:

… Life ain’t always what it seem to be
Words can’t express what you mean to me
Even though you’re gone, we still a team
Through your family, I’ll fulfill your dream

In the future, can’t wait to see
If you open up the gates for me
Reminisce sometime
The night they took my friend
Try to black it out but it plays again
When it’s real feelings’ hard to conceal
Can’t imagine all the pain I feel
Give anything to hear half your breath
I know you still livin’ your life after death

… It’s kinda hard with you not around
Know you in heaven smilin down
Watchin us while we pray for you
Every day we pray for you
Til the day we meet again
In my heart is where I’ll keep you friend
Memories give me the strength I need to proceed
Strength I need to believe …
I still can’t believe you’re gone
Give anything to hear half your breath
I know you still living you’re life, after death …

The second song is Eva Cassidy’s cover of Over The Rainbow, which is the Academy Award-Winning song written by Harold Arlen and E.Y. Harburg, and originally sung by Judy Garland, in the 1939 Academy Award-Nominated “Best Picture” film Wizard of Oz.

Eva Cassidy, like you, died in the prime of her life from cancer.  Eva was 33 years old when she died in 1996 from melanoma, the deadliest form of skin cancer.  During her life, she created and sung beautiful music in relative obscurity. After her death, millions of worldwide fans “discovered” her music and today celebrate her life.  The lyrics of this classic ballad celebrate our belief that you are now at peace in a beautiful place “somewhere over the rainbow,” along with the hope that we will one day be reunited with you:

Somewhere over the rainbow
Way up high
There’s a land that I heard of
Once in a lullaby

Some day I’ll wish upon a star
And wake up where the clouds are far behind me
Where troubles melt like lemondrops
Away above the chimney tops
That’s where you’ll find me

Somewhere over the rainbow
Bluebirds fly
Birds fly over the rainbow
Why then, oh why can’t I?

In Mitch Albom’s bestselling memoir Tuesdays With Morrie, Morrie Schwartz, who was suffering from terminal Lou Gehrig’s Disease, taught Albom (his former college student) an important lesson about how death reminds us to live fully each day with love. “As long as we can love each other, and remember the feeling of love we had, we can die without ever really going away,” he told Albom one Tuesday. “All the love you created is still there. All the memories are still there. You live on in the hearts of everyone you have touched and nurtured while you were here. Death ends a life, not a relationship.”

Libby, your memory, love, and inspiration live on in our hearts and minds.  Your physical life ended one year ago, but your relationship with us is eternal.  We will forever love you.

Libby Remick (1982 - 2008) Grieve not, nor speak of me with tears, but laugh and talk of me as if I were beside you there. -- Isla Paschal Richardson

Libby Remick (1982 - 2008) "Grieve not, nor speak of me with tears, but laugh and talk of me as if I were beside you there." -- Isla Paschal Richardson

I am requesting family members and readers to honor Libby by contributing at least $1.00 to ovarian cancer research via the Ovarian Cancer Research Fund (and PayPal).  To make a contribution, click on Kelly Ripa’s picture located on the left homepage sidebar, or simply CLICK HERE.


  • Ovarian cancer causes more deaths than any other cancer of the female reproductive system.
  • In 2009, the American Cancer Society (ACS) estimates that there will be approximately 21,550 new ovarian cancer cases diagnosed in the U.S.  ACS estimates that 14,600 U.S. women will die from the disease, or about 40 women per day.
  • Ovarian cancer is not a “silent” disease; it is a “subtle” disease. Recent studies indicate that some women may experience persistent, nonspecific symptoms, such as (i) bloating, (ii) pelvic or abdominal pain, (iii) difficulty eating or feeling full quickly, or (iv) urinary urgency or frequency. Women who experience such symptoms daily for more than a few weeks should seek prompt medical evaluation. To learn more about the warning signs and symptoms of ovarian cancer, CLICK HERE.
  • Ovarian cancer can afflict adolescent, young adult, and mature women, although the risk of disease increases with age and peaks in the late 70s. Pregnancy and the long-term use of oral contraceptives reduce the risk of developing ovarian cancer.
  • There is no reliable screening test for the detection of early stage ovarian cancer. Pelvic examination only occasionally detects ovarian cancer, generally when the disease is advanced. A Pap smear cannot detect ovarian cancer. However, the combination of a thorough pelvic exam, transvaginal ultrasound, and a blood test for the tumor marker CA125 may be offered to women who are at high risk of ovarian cancer and to women who have persistent, unexplained symptoms like those listed above.
  • If diagnosed at the localized stage, the 5-year ovarian cancer survival rate is 92%; however, only about 19% of all cases are detected at this stage, usually fortuitously during another medical procedure.
  • For women with regional and distant metastatic disease, the 5-year ovarian cancer survival rates are 71% and 30%, respectively. The 10-year relative survival rate for all stages combined is 38%.


*”Vox Populi,” a Latin phrase that means “voice of the people,” is a term often used in broadcast journalism to describe an interview of a “man on the street.”

In the spirit of Vox Populi, Libby’s H*O*P*E*™ searches online for original pieces of writing created by ovarian cancer survivors, survivors’ family members, cancer advocates, journalists, and health care professionals, which address one or more aspects of ovarian cancer within the context of daily life. The written pieces that we discover run the gamut; sometimes poignant, sometimes educational, sometimes touching, sometimes comedic, but always honest. The written piece may be an essay, editorial, poem, letter, or story about a loved one. In all cases, we have received permission from the writer to publish his or her written piece as a Libby’s H*O*P*E*™ Vox Populi weblog post.

It is our hope that the monthly Vox Populi feature will allow readers to obtain, in some small way, a better understanding of how ovarian cancer impacts the life of a woman diagnosed with the disease and her family. We invite all readers to submit, or bring to our attention, original written pieces suitable for publication as monthly Vox Populi features.

PhRMA Report Shows Record Number of Development Drugs to Treat Cancer; 63 Ovarian Cancer & 203 Solid Tumor Drugs Listed

“Responding to President Obama’s call for ‘a cure for cancer in our time,’ the Pharmaceutical Research and Manufacturers of America (PhRMA) delivered a new report today on medicines in the research pipeline for cancer. The report shows that America’s pharmaceutical research and biotechnology companies are testing a record 861 new cancer medicines and vaccines. The medicines listed in the report are being tested in human clinical trials or are awaiting approval by the U.S. Food and Drug Administration. [Libby’s H*O*P*E*™ : 63 Ovarian Cancer Drugs & 203 Solid Tumor Drugs are listed in the 2009 PhRMA report (pp. 51 – 55)]. …”

“New Report Shows Record Number of Medicines In Development to Treat Leading Causes of Cancer

phrmalogoDenver, CO (April 1, 2009) – Responding to President Obama’s call for ‘a cure for cancer in our time,’ the Pharmaceutical Research and Manufacturers of America (PhRMA) delivered a new report today on medicines in the research pipeline for cancer. The report shows that America’s pharmaceutical research and biotechnology companies are testing a record 861 new cancer medicines and vaccines. The medicines listed in the report are being tested in human clinical trials or are awaiting approval by the U.S. Food and Drug Administration. [Libby’s H*O*P*E*™ Note: 63 Ovarian Cancer Drugs & 203 Solid Tumor Drugs are listed in the 2009 PhRMA report (pp. 51-55)].

Nationwide, cancer is the second leading cause of death, affecting more than 10 million Americans, according to the National Cancer Institute. This year, more than half a million Americans are expected to die of cancer-more than 1,500 a day. In Colorado, the lifetime risk of cancer is 1 in 2 for males and 2 in 5 for females. The most commonly diagnosed cancer in the state is breast cancer, followed by prostate and lung cancer.

‘We released this report in Denver because of Colorado’s growing role in developing cancer medicines,’ said PhRMA Senior Vice President Ken Johnson, who unveiled the report at the State Capitol Building.

‘Oncology is one of Colorado’s core research competencies, so the President’s call to cure cancer resonates powerfully in our state,’ said Colorado Lt. Governor Barbara O’Brien. ‘We are proud that the cancer medicines now in the research pipeline in Colorado are contributing substantially to the incredible progress made in the last five years by biopharmaceutical companies in developing new and more effective cancer treatments. The nation must continue its strong commitment to the cutting-edge pharmaceutical research that will enable cancer patients to live longer, healthier, and more productive lives.’


Billy Tauzin, President and Chief Executive Officer, The Pharmaceutical Research and Manufacturers of America (PhRMA). PhRMA's mission is to conduct effective advocacy for public policies that encourage discovery of important new medicines for patients by pharmaceutical & biotechnology research companies.

‘I am one of those patients who was diagnosed with cancer and was given a new treatment that brought me from the brink of death back to life,’ says PhRMA President and CEO Billy Tauzin. ‘The men and women working for America’s pharmaceutical research companies are committed to developing new cancer medicines that, one day, could eradicate cancer all together.’

Cancer medicines being developed include 122 for lung cancer, the leading cause of cancer death in the United States; 107 for breast cancer, which is expected to strike more than 180,000 American women this year; 70 for colorectal cancer, which is the third most common cancer in both men and women; and 103 for prostate cancer, which this year is expected to kill 28,000 American men. Additional medicines target brain cancer, kidney cancer, ovarian cancer, pancreatic cancer, skin cancer, and others.

The medicines represent many cutting-edge approaches, including a drug that delivers a synthetic version of a substance derived from scorpions directly to brain tumor cells; a number of cancer vaccines; medicines that target and kill specific cancer cells; and treatments that activate the patient’s general immune system to destroy cancer.

‘Researchers are making exciting progress in the search for new cures and treatments for cancer. But these efforts are wasted if the medicines we develop aren’t accessible to patients who need them,’ said Johnson.

Help is available to patients in need through the Partnership for Prescription Assistance (PPA), a program sponsored by America’s pharmaceutical research companies. To date, the PPA has helped more than 5.7 million patients nationwide, including more than 72,000 people in Colorado. Since its launch in April 2005, the PPA bus tour has visited all 50 states and more than 2,500 cities to educate people about patient assistance programs.

The “Help is Here Express” is staffed by trained specialists able to quickly help uninsured and financially struggling patients access information on more than 475 patient assistance programs, including nearly 200 programs offered by pharmaceutical companies. When the “Help is Here Express” moves on, patients can visit PPA’s easy-to-use Web site ( or call the toll-free phone number (1-888-4PPA-NOW).

Click here to read Medicines in Development for Cancer 2009. [Adobe Reader PDF Doc.]

Read the backgrounder fact sheet here.


Pharmaceutical Research & Manufacturers of America

The Pharmaceutical Research and Manufacturers of America (PhRMA) represents the country’s leading pharmaceutical research and biotechnology companies, which are devoted to inventing medicines that allow patients to live longer, healthier, and more productive lives. PhRMA companies are leading the way in the search for new cures. PhRMA members alone invested an estimated $50.3 billion in 2008 in discovering and developing new medicines. Industry-wide research and investment reached a record $65.2 billion in 2008.

PhRMA Internet Address:

For information on stories of hope and survival, visit:

PhRMA en Español:

For information on how innovative medicines save lives, visit:

For information on the Partnership for Prescription Assistance, visit:

For information on the danger of imported drugs, visit:”

SourceNew Report Shows Record Number of Medicines In Development to Treat Leading Causes of Cancer, Press Release, Pharmaceutical Research and Manufacturers of America, April 1, 2009.