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	USE OF MAMMOGRAPHY LOW IN SURVIVORS AT GREATEST RISK OF BREAST CANCER RECURRENCE

Top Use of Mammography Low... Cancer Polidy: Health Care... FDA Advisors Recommend INTRON... FDA Establishes First... LIDAK Pharmaceuticals Says... Johnson, Ortho to Expand... Myriad Licenses MMAC1 Rights... Affymetrix, Oncormed Broaden...

The study, by Marilyn Schapira and Ann Nattinger of the Medical College of Wisconsin Cancer Center, followed national tumor registry and Medicare data for 30 months on 4,040 older American women diagnosed with regional, local, or earliest stage breast cancer in 1986-1987 and treated with surgery. The findings were presented at the annual national meeting of the Society of General Internal Medicine.

"Annual surveillance with mammography is recommended in breast cancer survivors, both to detect local recurrence and to detect a second primary cancer," Schapira said.

After controlling for patient-level factors such as age, race, disease stage and treatment group, and community-level factors such as income, education, and population, Schapira found that use of annual mammography was 72% lower among women treated with breast conserving surgery without radiotherapy. Other study conclusions were:

• Use of surveillance mammography among Medicare patients was lower than expected.
  
• African American women and women of older age or lower educational status were also less likely to undergo annual mammography.
  
• Efforts to increase mammography compliance should target older breast cancer survivors in addition to the general population.
  

Average age of the study subjects was 73.7 years. Sixty-two percent had local stage disease at diagnosis, 30% had regional disease and 8% had very early stage disease which had not spread beyond its original site. Ninety-five percent of the group were Caucasians, and 4% were African Americans. Seventy-five percent underwent mastectomy, 12.5% underwent breast conserving surgery with radiation, and 12.5% underwent breast conserving surgery without radiation. Overall, 38.9% of these women had a mammogram each year during the two-year study period, 25.5% had only one, and 35.6% had none.

While use of annual mammography was not associated with the stage of disease at diagnosis, use did decrease with age. Women between 65 and 69 were more than twice as likely to use annual mammography (47.4%) as women over 80 (22.5%). After controlling for patient and community-level factors, Schapira also found that use of annual mammography was 38% lower among African American women.

Ironically, those of all ages and races at highest risk for recurrence—because they had not had radiotherapy with their breast conserving surgery-had a dramatically lower annual mammography rate (14.1%) than both of the other treatment groups. Rates were 42.9% for women who had breast conserving surgery with radiotherapy and 42.5% for women who had mastectomies.

Schapira is assistant professor of medicine at the Medical College and practices in the division of general internal medicine at the VA Medical Center-Milwaukee. Nattinger is associate professor of medicine. Their work was supported by the U.S. Army Medical Research and Materiel Command.

	CANCER POLIDY: HEALTH CARE COST CONTAINMENT IMPEDES RESEARCH, PANEL SAYS

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Recent changes in the health care system have resulted in a loss of financial support for cancer research and training within clinical research centers, and limited care for the socioeconomically disadvantaged, the President’s Cancer Panel said in a recent report.

The report details the panel’s findings from four hearings during 1996 on the effects of managed care on cancer research, care, and training. The report was submitted to President Clinton last July, and publicly released last month.

"Recent and ongoing health system changes are demanding too high a price from the more that 1.3 million people diagnosed annually with cancer and the remainder of Americans at risk," the report said. "Short-term and short-sighted cost containment can and will impede the progress of the National Cancer Program in reducing the national cancer burden."

The panel’s concerns about the impact of managed care on cancer research include: loss of patient care income to pay for cancer care for the indigent; limited patient access to cancer care due to complex approval processes and the exclusion of investigational therapies, and growing disincentives for physicians to conduct clinical research and to train future researchers.

"Managed care has made positive contributions to the health care landscape—breaking runaway health care costs, accentuating the need for evidence-based medical care, and addressing the need for certain preventive services," the report said. "It appears, however, that these positive influences are not without their costs."

The panel made the following recommendations to control managed care’s negative impact on the quality of cancer care:

• "Measures must be taken to ensure that minorities, the poor, the elderly, the uninsured, and the under-insured are not excluded from access to appropriate cancer care as the health care system evolves."
  
• "Both the importance of and the ability to participate in all phases of clinical trials should be formally incorporated into the standards of care for cancer; appropriate trial participation should be an integral component of clinical guidelines for specific malignancies, and the ability to access such trials, when appropriate, should be independent of health care provider. Criteria are needed to define clearly the required review processes, objectives, and other characteristics of clinical trials acceptable for patient care cost reimbursement."
  
• "This coverage should be guaranteed through legislation and/or negotiated agreements at the Federal and state levels."
  
• "The costs of clinical research must be paid in order for the quality of health care to continue improving. These costs must be paid regardless of the structure and financing of the health care delivery system. All of the beneficiaries of clinical research—managed care and other payers; research sponsors including government, voluntary agencies, and the pharmaceutical and biotechnology industries; employer and employee participants, and other consumers—must bear their fair shares in its cost."
  
• "Given the evolving health care financing and delivery systems, mechanisms must be established to ensure support for the training of clinical cancer caregivers and researchers. This crucial intellectual resource and our nation’s world leadership in cancer research and care must not be allowed to deteriorate in the interest of short-term cost savings."
  
• "Partnerships among the pharmaceutical and biotechnology industries and the public and other private (e.g., voluntary) research communities should be encouraged, but as a nation, we must ensure that the questions with the most scientific potential, as well as those offering the greatest economic return, are addressed."
  
• "The process for appealing coverage decisions made by health plans must be simplified, standardized, and fully disclosed to participants in health plans of all types. Appeal decisions must be rendered expeditiously."
  
• "Consumer education at all levels—e.g., employers and the public—is needed to promote an understanding of the importance of clinical cancer research and a realization that the need to access such care can become a reality for any person. This understanding is needed to create public demand for access to effective cancer care and to foster health system competition based on access and quality rather than on cost alone."
  

The report, "Fighting the War on Cancer in an Evolving Health Care System," is available from the NCI office of the executive secretary of the President’s Cancer Panel, telephone: 301-496-1148; fax: 301-402-1508; e-mail: PRESCAN{at}nih.gov

	FDA ADVISORS RECOMMEND INTRON A APPROVAL FOR NON-HODGKIN’S LYMPHOMA

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An FDA advisory committee recommended unanimously to approve INTRON A (interferon alfa-2b, recombinant for injection) in combination with anthracycline-based chemotherapy for the treatment of low-grade follicular non-Hodgkin’s lymphoma (NHL). The Biological Response Modifiers Advisory Committee recommended approval of the drug based on data from a phase III trial conducted by the French Groupe d’Etude des Lymphomes Folliculaire (GELF).

INTRON A is sponsored by Schering-Plough Corp. of Madison, NJ.

The open-label randomized trial included 273 previously untreated patients with high tumor burden. The trial was conducted in 31 European medical centers between 1986 and 1991. Principal investigator on the study was Philippe Solal-Celigny, from the Laboratoire Central d’Hematologie, Centre Jean Bernard, Le Mans, France.

Data presented to the committee at a meeting October 17, 1997, showed INTRON A in combination with chemotherapy, when compared to chemotherapy alone, increased the median progression-free survival of patients with low-grade follicular NHL from 1.5 years to 2.9 years.

The GELF trial used a chemotherapy regimen of cyclophosphamide, doxorubicin, teniposide, and prednisone (CHVP). The FDA questioned whether use of CHVP over the CHOP regimen affected the significance of the data. The committee decided the use of CHVP did not influence the efficacy of the drug.

Adverse events associated with the INTRON A/CHVP regimen included dyspnea, paresthesia, neutropenia, asthenia, and polyuria. All adverse events were reversible, said Craig Tendler, clinical project director for oncology at Schering-Plough Research Institute. Four patients died during the trial due to events unrelated to treatment, Tendler said.

FDA representative Massimo Cardinali said chemotherapy in combination with interferon showed an advantage in progression-free survival, but the data do not support an improvement in overall survival.

FDA raised concerns over the substantial difference between the GELF chemotherapy regimen and standard CHOP chemotherapy, and noted an increase in toxicity and myelosuppression. The committee said interferon can be used effectively, but should be used cautiously.

Further comparative studies should be conducted before patients receiving CHOP therapy are given an interferon combination, said Janice Gabrilove, assistant attending physician, Memorial Sloan-Kettering Cancer Center, and temporary voting member of the committee. The committee voted unanimously to recommend approval for interferon as an adjunct to CHVP chemotherapy for the treatment of low-grade follicular NHL.

INTRON A has been approved for marketing in the U.S. for the treatment of chronic hepatitis B and C, malignant melanoma, hairy cell leukemia, AIDS-related Kaposi’s sarcoma, and condylomata acuminata.

	FDA ESTABLISHES FIRST COOPERATIVE RESEARCH AND DEVELOPMENT AGREEMENT WITH PHARMACEUTICAL FIRM

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The Food and Drug Administration said it has established its first Cooperative Research and Development Agreement (CRADA) with a pharmaceutical company. NeoPharm, Inc., of Lake Forest, IL, will collaborate with the agency for the clinical and commercial development of IL13-PE38QQR, a novel chimeric human protein that is being studied for the treatment of renal cell carcinoma and glioblastoma, the company said. The protein is a fusion of receptor-binding ligand interleukin 13 and a derivative of Pseudomonas exotoxin (PE38QQR), the company said. IL-13 is expressed by cancerous cells found in solid tumors. Combined with PE38QQR, the drug is expected to infiltrate and destroy cells expressing IL-13, the company said.

IL13-PE38QQR was developed through a collaboration between FDA, NCI, and the Milton S. Hershey Medical Center at Pennsylvania State University College of Medicine. NeoPharm also signed an exclusive worldwide licensing agreement with FDA and NIH to develop and commercialize the product. Terms of the agreement were not disclosed.

The first indications to be studied under the CRADA will be renal cell carcinoma and glioblastoma-solid tumors that heavily express IL-13, said Aquilar Rahman, chief scientific officer of NeoPharm. The company hopes to conduct later studies on Kaposi’s sarcoma, pancreatic cancer, and colorectal cancer, Rahman said.

The company said objectives of the CRADA will be to further define the activity of the IL-13-chimeric protein in vivo, and to expand the potential utility to other tumor types that express the IL-13 receptors. IL13-PE38QQR will target cancerous cells, while limiting toxicity to healthy cells. If the drug is effective, it could reduce the need for radical nephrectomy procedures for renal cell carcinoma, the company said. Radical nephrectomy removes the entire kidney, adrenal gland, surrounding fascia, and regional lymph nodes.

	LIDAK PHARMACEUTICALS SAYS VACCINE STIMULATES IMMUNITY

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A phase I/II study conducted by LIDAK Pharmaceuticals of La Jolla, CA, showed the LP2307 vaccine to be effective in stimulating immunity against melanoma tumors, the company said. The trial was conducted on patients with advanced stage IV malignant melanoma. The company said immunization with LP2307 appeared to result in stabilization and remission in some patients who received treatment.

The trial was conducted by Malcolm Mitchell, director of the Center for Biological Therapy and Melanoma Research at the Cancer Center of the University of California, San Diego, the company said. The study was designed to evaluate LP2307 at three dose levels for safety and tolerance and its ability to elicit tumor-specific immune T cell reactions against melanoma tumor cells.

The company said specific immunological activity was observed in 10 of 15 patients who could be evaluated for cytotoxic T cell responses against melanoma tumor cells. The patients exhibiting cytotoxic T cell activity generally had rises in such activity ranging from two- to tenfold above the baseline cytotoxic T cell activity prior to LP2307 treatment, the company said.

The company said LP2307 immunization resulted in stabilization and remission of disease in five of the study patients. The overall survival times of the patients in the study averaged 12.1 months, compared to the average life expectancy of eight months of patients with widespread stage IV melanoma. Seven of 16 study subjects are alive 9 to 20 months after initial treatment, the company said.

LP2307 is a synthetic solid-phase product made by adhering melanoma cell membrane components to uniformly sized microbeads. The technique, known as large multivalent immunogen, was invented by Matthew Mescher at Medical Biology Institute, the company said.

	JOHNSON, ORTHO TO EXPAND COLLABORATION WITH CTI

Top Use of Mammography Low... Cancer Polidy: Health Care... FDA Advisors Recommend INTRON... FDA Establishes First... LIDAK Pharmaceuticals Says... Johnson, Ortho to Expand... Myriad Licenses MMAC1 Rights... Affymetrix, Oncormed Broaden...

 
R.W. Johnson Pharmaceutical Research Institute and Ortho Biotech Inc., both Johnson & Johnson companies, said they will expand their lisofylline collaboration agreement with Cell Therapeutics Inc., of Seattle, WA. The agreement has been expanded to include development of CTI’s lead drug candidate to treat patients receiving induction chemotherapy therapy for acute myeloid leukemia, the companies said.

CTI recently completed a phase II randomized double-blind, placebo-controlled trial of lisofylline among patients undergoing high-dose induction chemotherapy to treat AML, the company said. The company said the trial showed a 50% reduction in the incidence of serious neutropenic infections among lisofylline patients when compared to placebo recipients. None of the patients in the lisofylline arm developed a fungal infection, the company said.

The original agreement called for the development and commercialization of lisofylline for preventing serious infections and mortality following high-dose radiation or chemotherapy accompanied by bone marrow transplantation. PRI funded 60% of development costs under the original agreement, the companies said. Under the expanded agreement, PRI will also fund 60% of development costs related to achieving FDA approval for lisofylline for the treatment of AML, the companies said.

Lisofylline is being developed to reduce the incidence and severity of the side effects of chemotherapy, including infection, mucositis, and mortality, the company said.

	MYRIAD LICENSES MMAC1 RIGHTS TO SCHERING-PLOUGH

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Myriad Genetics Inc., of Salt Lake City, UT, has licensed therapeutic rights to the Mutated in Multiple Advanced Cancers (MMAC1) gene to Schering-Plough Corp., the companies said.

Schering-Plough has initiated a research program to develop cancer therapeutics based on the MMAC1 gene and its biochemical pathway. Myriad will retain worldwide molecular diagnostic rights and will continue development of the diagnostic potential of the gene, the companies said.

The MMAC1 gene was discovered by Myriad and collaborators at M.D. Anderson Cancer Center and published in the journal Nature Genetics, in April 1997. MMAC1 was initially located by mapping DNA sequence deletions in glioblastomas. MMAC1 is involved in almost all cases of this disease, as well as in advanced cancers of the prostate, breast, and skin, the company said.

	AFFYMETRIX, ONCORMED BROADEN COLLABORATION

Top Use of Mammography Low... Cancer Polidy: Health Care... FDA Advisors Recommend INTRON... FDA Establishes First... LIDAK Pharmaceuticals Says... Johnson, Ortho to Expand... Myriad Licenses MMAC1 Rights... Affymetrix, Oncormed Broaden...

 
Affymetrix of Santa Clara, CA, and Oncormed Inc., of Gaithersburg, MD, have broadened the scope of their original collaboration in DNA chip-based cancer diagnostics, the companies said.

Under the new agreement, the companies will co-develop a GeneChip system for BRCA1 and BRCA2 genotyping. Affymetrix said it will license rights to the BRCA1 and BRCA2 genes for arrays from Oncormed. Affymetrix will supply Oncormed with GeneChip probe arrays that will simultaneously monitor the expression of up to 250 genes associated with cancer in patient tumor samples, the companies said.

The GeneChip system provides rapid genetic analysis using miniaturized, high-density arrays of DNA probes and proprietary software to analyze and manage genetic information, the companies said.

The original collaboration between Oncormed and Affymetrix focused on the development and validation of a p53 GeneChip system, a project which is nearing completion, the companies said. In August 1997, Affymetrix began selling p53 GeneChip systems for research purposes, and Oncormed soon will introduce a GeneChip-based p53 clinical testing service in its CLIA-certified laboratory, the companies said.

Under the new agreement, Affymetrix and Oncormed will contribute technology and funding to develop a GeneChip probe array and software for BRCA1 and BRCA2 genotyping, the companies said.

	FOOTNOTES

Top Use of Mammography Low... Cancer Polidy: Health Care... FDA Advisors Recommend INTRON... FDA Establishes First... LIDAK Pharmaceuticals Says... Johnson, Ortho to Expand... Myriad Licenses MMAC1 Rights... Affymetrix, Oncormed Broaden...

 
© 1997 The Cancer Letter, Inc., publishers of: The Cancer Letter with Cancer Economics and The Clinical Cancer Letter. P.O. Box 9905, Washington, DC 20016 USA; Telephone: 202-362-1809; Fax: 202-362-1681; Internet: subscrib{at}www.cancerletter.com

This Article Full Text (PDF) eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services E-mail this article link to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content