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Odds & Ends
Abstracts by Tom Swartz and Bruce Shriver
In this issue:
You can download a PDF copy of the program of the 13th Annual CTOS Meeting which was held in Seattle, Washington during 1-3 November 2007. The copy contains the detailed abstract of all of oral presentations and all of the poster sessions. Click here to download this file (it is a large file, approximately 2 MB). You can view the program on-line and download copies of many of the presentations by clicking here. The Liddy Shriver Sarcoma Initiative was invited to give a presentation on the Team Sarcoma Initiative in the Patient Advocacy session at the meeting. You can download a PDF copy of the presentation. We also had a poster in the poster session of the meetings. You can download a copy of the poster here. The poster is large, but you don’t need to print it out as the PDF version of it can easily be viewed using the Adobe Reader. You can use the magnifier feature of the Reader to enlarge any particular area on the poster for easy reading.
Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs Cancer care today often provides state-of-the-science biomedical treatment, but fails to address the psychological and social (psychosocial) problems associated with the illness. This failure can compromise the effectiveness of health care and thereby adversely affect the health of cancer patients. Psychological and social problems created or exacerbated by cancer ─ including depression and other emotional problems; lack of information or skills needed to manage the illness; lack of transportation or other resources; and disruptions in work, school, and family life ─ cause additional suffering, weaken adherence to prescribed treatments, and threaten patients’ return to health.
A range of services is available to help patients and their families manage the psychosocial aspects of cancer. Indeed, these services collectively have been described as constituting a “wealth of cancer-related community support services.”
Today, it is not possible to deliver good-quality cancer care without using existing approaches, tools, and resources to address patients’ psychosocial health needs. All patients with cancer and their families should expect and receive cancer care that ensures the provision of appropriate psychosocial health services. This report recommends ten actions that oncology providers, health policy makers, educators, health insurers, health plans, quality oversight organizations, researchers and research sponsors, and consumer advocates should undertake to ensure that this standard is met. You can read the report online free (use the link above) but you must pay to download it.
Participation of Adolescents With Cancer in Clinical Trials Adolescent patients with cancer reside in a “no-man’s land” between the world of pediatric oncology and that of “adult” medical oncology. As compared to younger and older patients, adolescents and young adults are under-represented on clinical trials. This relative lack of participation in clinical protocols has been associated to a lack of progress in survival improvement over the last years. One of the main reasons for the deficit in protocol enrolment and the worse outcome of adolescents (when compared in particular to children) is the lack of awareness by the public, community and healthcare systems that cancer may occur in this age group. However, physicians – inadequately trained or reluctant to care for adolescents – have important responsibilities. Most 15- to 19-year-olds diagnosed with cancer are treated at adult facilities, although two-thirds to three-fourths of their cancers are typical of those that occur in the pediatric age range. The best choice may be to treat them according to their type of tumor, not according to their age: “pediatric” tumors treated by pediatric oncologists, “adult” tumors by adult medical oncologists, regardless of the patient’s age. This solution, however, is probably appropriate for the tumor, but not necessarily for the patient. Adolescents are neither old children nor young adults, and are very complicated individuals, with unique socio-psychological problems and needs, that may be addressed only by dedicated professionals, adequately trained and supported. This article argues that the ultimate challenge is the development of a new discipline, adolescent/teenage and young adult oncology, devoted to the care of these patients. See also There is no reason to include age as an entry criterion for any clinical trial by Dr. Paul Myers in the July 2007 issue of ESUN and Adolescent and Young Adult Cancer Care by Dr. Karen Albritton in December 2004 issue of ESUN.
ARIAD Pharmaceuticals has launched an international Phase 3 clinical trial of deforolimus, a novel mTOR inhibitor, in patients with metastatic soft-tissue and bone sarcomas. The SUCCEED (Sarcoma Multi-Center Clinical Evaluation of the Efficacy of Deforolimus) trial is a randomized, double-blind, placebo-controlled study. Patients who are currently receiving chemotherapy for the treatment of their sarcoma may wish to discuss the SUCCEED trial with their doctors to see if it may be right for them. Key eligibility criteria:
For more information about the trial or to find a trial site nearby, you can visit the SUCCEED trial webpage or call toll-free 1-877-621-2302 or internationally 1-617-621-2302 or email Ariad.
On November 3th, Keryx Biopharmaceuticals, Inc. presented preliminary data demonstrating the tolerability and clinical activity of KRX-0401 (perifosine) in patients with refractory, rare sarcomas at the Annual Meeting of the Connective Tissue Oncology Society. In an oral presentation entitled "A PHASE II TRIAL OF PERIFOSINE IN PATIENTS WITH CHEMO-INSENSITIVE SARCOMAS: PRELIMINARY RESULTS," Dr. Joseph Ludwig Assistant Professor, Dept of Sarcoma, MD Anderson Cancer Center reported on preliminary Phase 2 data in which single agent perifosine demonstrated a 40% overall clinical benefit (Stable Disease > 3 months) in these subsets of patients. Assessment of response was completed by both, RECIST and Choi criteria, and results by sarcoma subtype as follows:
Perifosine was also well tolerated with the most common grade 1 & 2 adverse events reported as nausea, vomiting, diarrhea and fatigue.
Commenting on the data, Dr. Craig Henderson, President of Keryx Biopharmaceuticals stated, "We continue to remain encouraged by the demonstrated clinical activity of perifosine in these rare but unresponsive sarcomas. We are excited to be working with the team of SARC investigators on this important clinical study and look forward to completing accrual to all study arms in 2008.
In prior studies, KRX-0401 (perifosine) has been shown to be quite active in the treatment of soft tissue sarcoma (ASCO 2007). Responding patients experienced very little toxicity and the duration of responses observed varied from 6 months to more than 18 months. Several types of sarcomas that responded to perifosine in prior trials are particularly interesting because they are generally thought to be unresponsive to chemotherapy and no treatment has been approved for them by the FDA. In this ongoing study, the single agent activity of perifosine is being evaluated in patients with chondrosarcoma, alveolar soft part sarcomas and extra-skeletal myxoid chondrosarcomas. Patients are being treated with KRX-0401 (100 mg oral daily) until disease progression. Each of the three sarcoma histology arms has met response criteria during the early phases of the study to continue enrollment up to 37 patients. In these studies, partial responses occurred in patients with sarcoma subtypes that have been traditionally unresponsive to conventional therapy.
This Phase II study was initiated in December 2006 and is being conducted by the Sarcoma Alliance for Research through Collaboration (SARC) multi-center network, which includes nationally recognized sarcoma centers and investigators throughout the United States. Dr. Dejka M. Araujo, Assistant Professor in the Department of Sarcoma at MD Anderson Cancer Center in Houston, Texas is acting as Principal Investigator for the study.
NanoValent Pharmaceuticals of Bozeman, Montana has entered into collaboration with oncology researchers at Children's Hospital of Los Angeles. The partnership will focus on generating efficacy data in murine models of Ewing's Sarcoma and Acute Lymphoblastic Leukemia utilizing NanoValent's drug candidates NANO-EW and NANO-ALL. NANO-EW, NanoValent's lead cancer drug candidate is a transferrin surface targeted nanoparticle loaded with the chemotherapeutic SN38. The Company's primary indication is Ewing's Sarcoma. However, the firm intends to expand development efforts to include non-small cell lung cancer and hepatocellular carcinoma. NANO-ALL is a transferrin surface targeted nanoparticle delivering siRNA fragments intended to silence gene sequences specific to acute lymphoblastic leukemia. The Company is developing therapeutics against pediatric and adult cancers using proprietary polymerized liposomal nanoparticle (PLN) drug delivery technology.
The purpose of this study was to explore negative and positive consequences of cancer during adolescence experienced two years after diagnosis. Two years after diagnosis 38 persons, 15-21 years old, were asked two questions over the telephone: What, if anything, is bad for you due to the cancer disease? and What, if anything, is good for you due to the cancer disease? The answers were analyzed by content analysis. Four categories of negative experiences were identified: a problematic body; unpleasant thoughts and feelings; outside the circle of friends; and difficulties with schoolwork. Six categories of positive experiences were identified: a more positive view of life; good self-esteem; knowledge and experience with regard to disease and hospital care; good relations; broader perspectives; and material gains. Thus, those struck by cancer during adolescence experience not only a number of negative, but also positive, consequences of the cancer disease and its treatment.
Symptom Clusters in Patients With Newly-Diagnosed Brain Tumors A symptom cluster comprises three or more concurrent symptoms. There is a paucity of symptom cluster research in cancer patients. Data from a previously conducted clinical trial were analyzed to search for symptom clusters. This phase III, placebo-controlled, double-blind, prospective, randomized clinical trial of 66 patients assessed the effect of prophylactic d-threo-methylphenidate (d-MPH) on quality of life (QOL) in newly diagnosed brain tumor patients receiving brain radiation therapy. Patients received 5–15 mg of d-MPH or placebo twice daily starting on week 1 of radiation therapy and continuing for 8 weeks post radiotherapy. QOL data were collected at baseline; the end of radiation therapy; and 4, 8, and 12 weeks following radiation therapy using the Functional Assessment of Cancer Therapy (FACT), the FACT-Brain subscale, and the Center for Epidemiologic Studies Depression Scale. Exploratory factor analysis, multidimensional scaling (MDS), and cluster analysis were used to search for symptom clusters. The trial failed to show a treatment effect; patients receiving d-MPH or placebo were analyzed together to search for clusters. Two symptom clusters were identified using exploratory factor analysis—a language cluster including difficulty reading, writing, and finding the right words and a mood cluster including feelings of sadness, anxiety, and depressed mood; these clusters were supported by MDS and cluster analysis. These results suggest that interventions that target both cognitive function and mood should be considered in this patient population. Further research on symptom clusters in brain tumor patients is needed.
Late effects in adult survivors of childhood cancer: the need for life-long follow-up The purpose of this study was to assess health status and health-related quality of life (HRQoL) in childhood cancer survivors who were not involved in regular long-term follow-up. One hundred and twenty-three long-term survivors, median age 33 (19–50) years, follow-up 27 (9–38) years, were recalled to the long-term follow-up clinic. Most of them were treated in the period 1970–1990. Late effects were graded using the Common Terminology Criteria for Adverse Events, version 3 (CTCAEv3). HRQoL was assessed by RAND-36. Socio-economic factors were compared with data from Statistics Netherlands (CBS). The Results were as follows: Grade 1–2 late effects were found in 54% of the survivors, grade 3–4 in 39%, two or more late effects in 70% and grade 2–4 previously unknown late effects in 33%. Survivors had significantly lower scores on RAND-36 compared with controls. The authors Conclude: As nearly 40% of these long-term childhood cancer survivors suffer from moderate to severe late effects and 33% had previously unknown late effects it is worthwhile recalling these patients to follow-up. Where and by whom this follow-up can best be done is still a question that needs to be answered.
This study compared the outcome of pediatric patients with adult-type soft tissue sarcomas with that reported for adults, taking into account the effect of established prognostic factors. The actual mortality of the study’s series was compared with that predicted by the nomogram developed for adults at the Memorial Sloan Kettering Cancer Center. From a previously-published series of 182 patients <18 years, 112 cases fulfilling the criteria for the nomogram application were selected. The Results were as follows: Actual 10-year mortality for the series was 29%, compared with a 16% predicted mortality. The effect of individual covariates was qualitatively consistent with that of adults, but the unfavorable prognostic effect of tumor size was stronger in pediatric cases. The authors Conclude: The variables known to have a prognostic role in adults are relevant also in children. The worse outcome observed in their series might be explained by the stronger adverse effect of tumor size in young patients.
Ways to Teach Approved Drugs New Tricks Although all cancers are not alike, most share common causes, whether it is the result of a genetic mutation or faulty biochemical signaling pathway. For that reason, drugs developed specifically for one disease might have an impact on many others. Increasingly, researchers are discovering ways of combining new and existing drugs to fight cancer – broadening the targets of already-approved targeted therapeutics.
On October 25th at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, researchers presented the results of some of these investigations, whether it is finding a new use for the immunosuppressant rapamycin or adapting the use of approved antibodies to reach the same targets within different cancers.
Researchers at St. Jude Children’s Research Hospital in Memphis, Tennessee, have discovered that an engineered antibody, in combination with rapamycin, may offer treatment for rhabdomyosarcoma, osteosarcoma, and Ewing’s’ sarcoma. The antibody, called CP-751871, is currently in a Phase III trial by its developer, Pfizer, Inc., while rapamycin, an approved immunosuppressant, is also under study for its anti-cancer properties.
Combined, the researchers believe, the two therapeutics act in a way that helps to promote apoptosis, a series of internal signals within a cell that cause its self-destruction. CP-751871 binds to – and thereby blocks the action of – a cell surface protein called insulin-like growth factor receptor (IGF-1R), which research has shown to be a part of a process that limits apoptosis. Rapamycin has been shown to inhibit mTOR, a protein involved in regulation of cell growth, proliferation and survival. There is increasing evidence that activation of cellular proteins upstream or downstream of mTOR is critical in the process of cancer progression.
“Together, the two therapeutics seem to have a synergistic effect in human sarcomas, combined they function more strongly than either drug alone,” said Raushan T. Kurmasheva, Ph.D., a post-doctoral fellow at St. Jude. “We are looking to extend our studies to include more sarcoma models, but we believe this looks like a promising clinical application for these drugs.”
According to Kurmasheva, the combined therapy could be a breakthrough in treatment of human sarcomas in general and childhood sarcomas, in particular. Both Ewing’s sarcoma and osteosarcoma are cancers of the bone and connecting tissue that are most frequently diagnosed in teens. Rhabdomyosarcoma is a rare disease that primarily affects children between the ages of one and five, but which can also strikes adolescents. While prognosis for childhood sarcomas is generally good, if caught early, children with these diseases face a grim prognosis if the cancer metastasizes, Kurmasheva says.
With support from the National Cancer Institute and Pfizer, the St. Jude researchers began their study in cell cultures of both cancer types. The antibody, alone, significantly retarded cell growth, they found. In animal models of sarcoma, both drugs curbed tumor growth. The two drugs combined, however, induced complete regression of established tumors. Due to the encouraging results, Kurmasheva and her colleagues are looking to expand their research to other animal models as well as look for biomarkers that could indicate positive response to treatment in a clinical setting.
Palliative care in adolescents The cure rate of cancer in adolescents is high but between 10% and 40% of them will develop incurable disease depending on tumor type and prognostic factors. These patients will need palliative care defined as supportive care to optimize comfort, function and social support of the patient and the family. This paper states that palliative care should include attention to symptom control, psychosocial and spiritual issues and should be given by a multidisciplinary team. Palliative care in adolescents should also take care of the specific physical and psychosocial developmental changes in this age group. Furthermore, specific spiritual, ethical and legal issues have to be taken into account.
Former Senator Donates $1.5 Million In Son's HonorThe parents of Robert Wallace Miller hope their $1.5 million gift to the Purdue Cancer Center will help keep the memory of their son alive. Former Indiana Sen. V. Richard "Dick" Miller and his wife, Jane Miller, made the donation in honor of their late son, "Robbie," who succumbed to a rare form of cancer in 1976. He was 11 years old.
"The doctor couldn't figure out what was wrong with him," said Dick Miller, who earned his bachelor's degree in science from Purdue in 1963. "In October, he stopped breathing, and we couldn't revive him." A fast-growing, highly malignant tumor attached itself to the muscle tissue in Robbie's chest, which caused him to suffocate. Since then, the couple has sought ways to fight cancers of all kinds. In 1995, the Millers established the Robbie Chair at the Indiana University Cancer Center. "We want people to be in the preventative mode as well as a cure mode," Dick Miller said. "We hoped this gift would provide the brain power to be able to hire the best of the best and attack these diseases the best way we can."
Cancer Center director Timothy Ratliff said the gift will help attract top scientists who he hopes will be able to develop new technology and therapeutics in bladder cancer research. "The Millers' donation and donations like this by people who generously support cancer research allow us to investigate new and novel ideas," Ratliff said. "But the idea has to be developed before we can get funding from government agencies."
Ratliff said leading scientists in nanotechnology and cancer research have to generate large amounts of data before they can be competitive for more significant grants. But with increasing support from people like the Millers, he said, survival rates for cancer continue to improve. "We are making a difference."
V4N6 ESUN Copyright © 2007 Liddy Shriver Sarcoma Initiative. |
