A vaccine made from autologous tumor cells genetically modified to secrete human granulocyte-macrophage colony-stimulating factor (GM-CSF) completely arrested non-small-cell lung cancer (NSCLC) in three patients with advanced disease, according to a study in the Feb. 18 Journal of the National Cancer Institute. Chemotherapy had already failed for two of the three "complete responders" in the study, and two others had a fairly uncommon NSCLC subtype. The vaccine had promising effects on overall survival and disease progression in the other advanced-stage patients but failed to show any benefit for patients in this small, phase I/II study who had early-stage NSCLC.
Success in manufacturing the vaccine was somewhat limited, and there was also dramatic variability in the vaccine's ability to secrete GM-CSF (which stimulates the body's immune system to produce cancer-fighting cells). Overall, only 43 patients were vaccinated, 10 with early-stage disease and 33 with advanced disease. "Only vaccine-associated GM-CSF secretion was statistically significantly associated with improved survival" in cohort B, the researchers wrote.
Patients with renal cell carcinoma confined to the kidney who underwent radical nephrectomy had higher progression-free survival rates when treated with an autologous tumor-based vaccine than those who did not receive a vaccine, German researchers reported in the Feb. 21 issue of The Lancet. Nephrectomy (removal of part or all of the kidney) is the standard treatment for renal cancer. Adjuvant treatments post nephrectomy, including radiotherapy and chemotherapy, have not proven to help prevent disease recurrence. Around half of patients with renal cancer have disease recurrence within 5 years when treated according to the current standard of care.
This study, a phase III trial, which was not blinded or placebo-controlled, involved nearly 560 patients scheduled for radical nephrectomy from 55 medical centers across Germany. Before surgery, all patients were randomly selected to receive a vaccine made from their own tumor cells or no additional treatment. Overall, 343 patients successfully completed the entire protocol. At five years of follow-up, progression-free survival rates for patients at all tumor stages were 77.4 percent in the vaccine group and 67.8 percent in the control group. At 70 months, those rates were 72 and 59.3 percent, respectively.
In a related commentary, Drs. Mayer Fishman and Scott Antonia from the H. Lee Moffitt Cancer Center and Research Institute called the study's observations "an immunological breakthrough." But they also argued that methodological shortcomings could limit interpretation of the data.
The cause of a leukemia cluster in 16 children who lived in Churchill County, Nev., is unknown, according to an expert panel that reviewed the findings of an intense investigation into the cluster. The expert panel was initially convened in 2001 to advise the Nevada State Health Division on possible follow-up actions and priorities for its investigation of the "Fallon cluster," named after the largest town in Churchill County. The panel's final report was released last month. The 16 cases of leukemia were diagnosed between 1997 and July 2002. Acute lymphoblastic leukemia (also called acute lymphocytic leukemia, or ALL) was the diagnosis in all cases except one, and all 16 cases occurred in children who were resident in Churchill County at the time of or at some point prior to their diagnoses.
At the expert panel's recommendation, extensive environmental testing and pathway exposure evaluations were performed to address community members' concerns about the health of their environment, explained Dr. Malcolm Smith, a member of the expert panel and head of the NCI Cancer Therapy Evaluation Program's Pediatric Section.
"The results from this testing were that the levels of most contaminants measured were not elevated compared with national norms or existing environmental standards, and none of the measured contaminants were associated with the occurrence of leukemia," Dr. Smith said. "Arsenic, previously known to be present at high levels in the community, was noted as an ongoing environmental health hazard and one that the community is addressing, though arsenic is not likely related to the leukemia cluster."
The panel also considered whether the cluster could have occurred by random chance - something that was not ruled out, but that appears unlikely, Dr. Smith explained. "The Fallon cluster is the most striking cluster involving childhood ALL that has been reported," he said. "A paper published online by Environmental Health Perspectives (search for: 10.1289/ehp.6592) reports that a cluster of this magnitude would be expected to occur in the United States by chance about once every 22,000 years. So, while it is true that chance cannot be excluded as a cause, it is also true that chance is not likely to be the sole explanation for the cluster."
The expert panel did not recommend specific follow-up research on the cluster at this time but did encourage continued childhood leukemia etiologic research. "The data and biological specimens that have been collected for the Fallon cluster may be useful in evaluating new hypotheses that are developed about the causes of childhood ALL clusters," Dr. Smith said.
Additional information about the Churchill County leukemia cluster is available at the Nevada State Health Division Web site at http://health2k.state.nv.us/healthofficer/leukemia/fallon.htm.