News Release

Other highlights in the October 20 JNCI

Peer-Reviewed Publication

Journal of the National Cancer Institute

High Birth Weight Associated With Increased Risk of Acute Lymphoblastic Leukemia

A new study has found that high birth weight is associated with an increased risk of childhood acute lymphoblastic leukemia (ALL) but not an increased risk of acute myeloid leukemia (AML).

The development of ALL and AML in children is likely to begin in utero, but few risk factors have been identified. Using data from health registers in Denmark, Iceland, Norway, and Sweden, Lisa Lyngsie Hjalgrim, M.D., of the Statens Serum Institut in Copenhagen, Denmark, and colleagues conducted a case–control study of more than 2,000 children with ALL or AML and their siblings and more than 10,000 control subjects and their siblings.

They found an association between birth weight and risk of ALL overall, as well as with B-cell and T-cell types of ALL. However, children with ALL did not weigh more than their siblings. There was not a clear association between birth weight and risk of childhood AML.

Contact: Lisa Lyngsie Hjalgrim, Statens Serum Institut, 45-32-68-39-51, lih@ssi.dk

Study Suggests an Effective Treatment for Overdose of Intrathecal Methotrexate

An injection of methotrexate into the spinal fluid is used in some cancers to prevent the spread of tumors to the tissues that cover the brain and spinal cord. The bacterial enzyme carboxypeptidase G2 is effective for treating rare but potentially fatal accidental overdoses of methotrexate given for this purpose, according to a new study.

Accidental overdoses of methotrexate administered intrathecally--by injection into the spinal fluid--can occur from medication preparation errors or when the drug is prescribed for systemic administration but administered intrathecally. Carboxypeptidase G2 rapidly hydrolyzes methotrexate into inactive metabolites and has been used to lower plasma levels of methotrexate in patients with renal dysfunction after systemic administration of high doses of methotrexate.

To see if intrathecal carboxypeptidase G2 could be used to treat accidental overdoses of intrathecal methotrexate in humans, Brigitte C. Widemann, M.D., of the National Cancer Institute, and colleagues administered the enzyme to seven patients 3 to 9 hours after an accidental overdose. Symptoms from the methotrexate overdose included seizures and coma. After administration of the enzyme, concentrations of methotrexate in the patients' cerebrospinal fluid decreased rapidly by 98%. All patients recovered completely from the intrathecal methotrexate overdose except two patients who had minor short term memory impairments. The authors conclude that intrathecal carboxypeptidase G2 appears to be effective for treating accidental intrathecal methotrexate overdoses.

Contact: National Cancer Institute Press Office, 301-496-6641, NCIPressOfficers@mail.nih.gov

Accelerated Approval of Oncology Drugs Reviewed

The accelerated approval process of the U.S. Food and Drug Administration allows for the approval of drugs for serious or life-threatening diseases based on surrogate endpoints so that drugs may reach patients more quickly. After approval is granted, however, drug companies are required to complete studies designed to confirm a drug's clinical benefit. In a review of the FDA's accelerated approval process for oncology drugs, Ramzi Dagher, M.D., of the Center for Drug Evaluation and Research at the FDA, and colleagues summarize the agency's experience with 22 accelerated approvals and discuss study designs and populations evaluated in the approval process. They also emphasize the need for the FDA and drug companies to integrate the accelerated approval process into a comprehensive drug development plan.

There is also a related JNCI News article on the accelerated approval process in this issue.

Contact: Ramzi Dagher, Center for Drug Evaluation and Research, 301-827-1543, dagherr@cder.fda.gov

Study Finds Combination of Molecules Has Potential for Treatment of Non–Small-Cell Lung Cancer

Insulin-like growth factor binding protein 3 (IGFBP-3)--a natural inhibitor of lung cancer cell survival and growth--is frequently decreased in lung cancers, a trait associated with poor prognosis and survival. A potential obstacle to treating lung cancer patients with IGFBP-3 is that cancer cells can become nonresponsive to the protein in a process mediated by the oncogene Ras. In a new study, Ho-Young Lee, Ph.D., of the University of Texas M. D. Anderson Cancer Center in Houston, and colleagues found that the combination of IGFBP-3 and SCH66336, a molecule that blocks the early stages of the activation of Ras, was associated with increased apoptosis and decreased tumor volume when tested in non–small-cell lung cancer (NSCLC) cell lines and in mouse model. They conclude that additional studies exploring the potential of this combination of molecules as a treatment for NSCLC are warranted.

Contact: Laura Sussman, M. D. Anderson Cancer Center, 713-745-2457, lsussman@mdanderson.org

Also in the October 20 JNCI:

  • Ductal Lavage May Not Detect Breast Cancer, Study Finds: http://www.eurekalert.org/emb_releases/2004-10/jotn-dlm101404.php
  • Study Examines Reasons for Late-Stage Breast Cancers: http://www.eurekalert.org/emb_releases/2004-10/jotn-ser101404.php
  • Chemotherapy, But Not Tamoxifen, Associated With Stroke Risk After Breast Cancer Treatment: http://www.eurekalert.org/emb_releases/2004-10/jotn-cbn101404.php

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    Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oupjournals.org/.


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