National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
November 29, 2011 • Volume 8 / Number 23

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Cancer Research Highlights

Survey of Oncologists Suggests Lack of Progress in Cancer Pain Management

Results of a national survey show that U.S. medical oncologists receive inadequate training in cancer pain management and perceive numerous barriers to managing pain optimally in their patients. The results of the survey, conducted by Dr. Brenda Breuer and her colleagues at Beth Israel Medical Center in New York, were published online November 15 in the Journal of Clinical Oncology (JCO).

The survey, which was modeled in part after a 1990 survey conducted by the Eastern Cooperative Oncology Group (ECOG), “demonstrated disturbingly little progress” in attitudes and practices related to pain management among medical oncologists over the last 20 years, according to an accompanying editorial. Yet during this time, guidelines for managing cancer pain have been developed and disseminated, continuing medical education on the subject has become common, and access to pain specialists has increased, the study authors noted.

Dr. Breuer and her colleagues mailed the anonymous survey to a randomly selected, geographically representative sample of 2,000 medical oncologists, and 610 usable surveys (32 percent) were returned.

In the survey, oncologists gave their medical specialty good marks (a median rating of 7 on a scale of 0 to 10) for relieving cancer pain but rated their peers as more conservative than themselves in prescribing opioid drugs to manage pain. And although most respondents agreed with the basic principles of pain management, their responses to two challenging clinical scenarios presented in the survey suggest that a majority of oncologists are deficient in knowledge about opioids, the study authors reported.

As in the 1990 survey, “oncologists continue to perceive that the most significant barriers to adequate pain management are poor pain assessment, patient reluctance to report pain, and patient reluctance to take analgesics,” Dr. Breuer and her co-authors wrote. Furthermore, “poor ratings of pain management training [during medical school and residency] have barely changed” in the two decades since the 1990 ECOG survey.

“There is a worldwide outcry for adequate cancer pain management, yet the skills of many oncologists remain inadequate in this domain,” commented the authors of the editorial, Dr. Jamie H. Von Roenn of Northwestern University, who was also the lead author of the ECOG survey, and Dr. Charles von Gunten of the Institute of Palliative Medicine at San Diego Hospice. “If we are to provide patients the care they deserve, we must not just integrate training in pain management into every fellowship program, we must expect oncologists to practice what they learn.”

(For more information, listen to this JCO podcast, in which Dr. Eduardo Bruera, chair of the Department of Palliative Care and Rehabilitation Medicine at the University of Texas M. D. Anderson Cancer Center, discusses the survey’s findings and offers recommendations on addressing some of the problems identified by the survey.)

Trial Confirms Efficacy of HPV Vaccine, Shows Cross-Protection

End-of-trial results from a trial testing Cervarix, a vaccine against human papillomavirus (HPV) types 16 and 18, showed that the vaccine continued to provide substantial protection against cervical precancers 4 years after vaccination. Cervarix provided almost complete protection in young women who had no evidence of exposure to HPV at the time of vaccination. The vaccine provided less protection for the total vaccinated cohort and was less effective with increasing age at vaccination. These findings reflect the vaccine’s lack of effectiveness against infections acquired before vaccination.

The vaccine also partially protected women against four types of HPV that are not targeted by the vaccine. (Although HPV-16 and -18 cause about 70 percent of cervical cancers worldwide, as many as 15 HPV types can cause cancer.) These results from the PATRICIA trial (Papilloma Trial against Cancer in Young Adults) were published online November 9 in Lancet Oncology in two separate papers, available here and here.

The PATRICIA trial enrolled 18,644 young women between the ages of 15 and 25 from 14 countries. The participants were randomly assigned to receive either three doses of Cervarix or three doses of a hepatitis A vaccine as a control. Results from the interim analysis, published in July 2009, showed that the vaccine greatly reduced the risk of grade 2 cervical intraepithelial neoplasias and higher (CIN2+).

The new analysis shows that, 4 years after vaccination, Cervarix provided complete protection against grade 3 cervical intraepithelial neoplasias or higher (CIN3+) associated with HPV-16 and -18 among women who had no evidence of exposure to HPV. The vaccine provided strong protection against CIN3+ caused by other HPV types in this same group of women. Among the total cohort of women who received at least one dose of Cervarix, some of whom may have had prior exposure to HPV, the vaccine provided some protection. (See the table below.)

Cervarix Vaccine Efficacy among Women Who Received at Least One Dose of Cervarix

 Women with no evidence of HPV exposure at baselineWomen who may have had prior exposure to HPV
Against CIN3+ associated with HPV-16 and -18100 percent45.7 percent
Against all CIN3+, regardless of HPV type93.2 percent45.6 percent
Against all adenocarcinoma in situ100 percent76.9 percent

The vaccine provided cross-protection against HPV-33, HPV-31, HPV-45, and HPV-51, all cancer-causing types of the virus. The researchers speculate that the observed cross-protection may be due either to the vaccine adjuvant (a substance that stimulates the immune system) or to similarities among proteins found on the surfaces of different HPV types.

In an accompanying editorial, Drs. Mark Schiffman and Sholom Wacholder of NCI’s Division of Cancer Epidemiology and Genetics, who were involved with the NCI Costa Rica HPV vaccine trial, noted the importance of the PATRICIA trial results. They also stated that “the practical aspects of vaccine uptake are now the most important issue in HPV vaccine research from a public health perspective.” To increase vaccine uptake in the developing world, where 90 percent of cervical cancer cases occur, next-generation HPV vaccines will need to be less expensive, provide protection in a single dose, and/or be stable without refrigeration, they explained.

Further reading: “Second Cervical Cancer Vaccine Protects against Additional HPV Types” and “Use and Acceptance of HPV Vaccine Still a Work in Progress

Genetic Study Yields Clues to Neuroendocrine Prostate Cancer

Researchers have identified a signaling pathway that may play an important role in neuroendocrine prostate cancer (NEPC), a very rare but aggressive form of the disease. Based on this discovery, the researchers tested a drug that inhibits the pathway and observed anticancer effects in two model systems. The findings appear in the November issue of Cancer Discovery.

Most cases of NEPC, which accounts for a small percentage of prostate cancers, arise following hormone therapy for prostate adenocarcinoma. To better understand the origins of the disease, Dr. Himisha Beltran of Weill Cornell Cancer Center and her colleagues profiled the gene-expression patterns of 7 NEPC tumors, 30 prostate adenocarcinomas, and 5 benign prostate tissue samples.

When they compared NEPCs and prostate adenocarcinomas, the authors found “dramatic differences” in the expression of certain genes, as well as differences in the number of copies of some genes. Two genes emerged as particularly interesting suspects in the disease—the AURKA gene, which encodes a protein called aurora kinase A and has been implicated in other cancers, and MYCN, another cancer-associated gene.

The researchers confirmed the association of AURKA expression with NEPC by analyzing benign prostate tissue and prostate tumors from a separate, larger cohort of patients. They concluded that the protein products of AURKA and MYCN may work together to induce characteristics of NEPC in prostate cancer cells.

Aurora kinase inhibitors are being evaluated in clinical trials, and the researchers tested one of these drugs against prostate adenocarcinoma and NEPC cells grown in laboratory culture as well as in mice bearing xenograft tumors derived from these cells. In the laboratory experiments, NEPC but not prostate adenocarcinoma cells were sensitive to the inhibitors; in the mice, the inhibitors caused tumor shrinkage of NEPC but not prostate adenocarcinoma xenograft tumors. In addition, drug treatment suppressed the expression of markers of neuroendocrine cells.

“The next step is to initiate a clinical trial,” said Dr. Beltran, who noted that there are no standard therapies for NEPC and that most patients die within a year of diagnosis. A small percentage of patients with prostate adenocarcinomas also show increased expression of the AURKA and MYCN genes, and these patients could be candidates for aurora kinase inhibitors as well, Dr. Beltran explained.

Previous studies have indicated that NEPCs and prostate adenocarcinomas may share the same cell of origin. It is known, for instance, that a genetic rearrangement often found in prostate adenocarcinomas is present at roughly the same rate in NEPCs. The precise number of cases of NEPC is unknown, however, in part because patients with advancing prostate cancer do not always have a biopsy, which is how NEPC is diagnosed.

The study authors cited evidence that long-term androgen deprivation therapy may promote the transformation of prostate cancer cells into NEPC. This suggests that “with the recent introduction of new highly potent androgen deprivation therapies into the clinical arena, the incidence of NEPC may escalate,” they noted.

“The current study is a stepping stone toward identifying neuroendocrine prostate cancer that is usually missed using regular screening modalities,” commented Dr. Sudhir Srivastava, who heads NCI’s Early Detection Research Network. “Understanding the biology of neuroendocrine prostate cancer will lead to better clinical management of this rare form of the disease.”

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