National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
March 24, 2009 • Volume 6 / Number 6

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Cancer Research Highlights

Three-Drug Regimen May Preserve the Voice Box in Larynx Cancer

Induction chemotherapy with a combination of three drugs significantly improved preservation of the larynx in patients with larynx and hypopharynx cancers compared to a commonly used two-drug regimen, French researchers reported. The larynx is commonly called the “voice box” because it is where sound is generated; its removal dramatically impairs speaking and swallowing. The findings were published online March 24 in the Journal of the National Cancer Institute.

The results come from a phase III randomized trial in which more than 200 patients with operable, locally advanced larynx or hypopharynx cancer were given an “induction chemotherapy” regimen—that is, treatment prior to “definitive” therapy with radiation or chemotherapy and radiation combined. Patients were assigned to either the three-drug combination of docetaxel, cisplatin, and 5-fluorouracil (TPF) or cisplatin and 5-fluoruracil (PF) alone for induction. In the trial, patients who responded to either induction chemotherapy regimen underwent subsequent radiation therapy, with or without chemotherapy; nonresponders underwent surgery.

At a median follow-up of 3 years, larynx preservation was 70.3 percent in patients assigned to the TPF regimen and 57.5 percent in patients assigned to PF. Patients in the TPF arm also had a better overall response rate than patients in the PF arm, 80.0 percent versus 59.2 percent, although there was no statistically significant difference in overall or disease-free survival. Side effects such as neutropenia and febrile neutropenia were worse in the TPF arm.

Although the trial has its limitations, explained Dr. Arlene Forastiere from the Sidney Kimmel Comprehensive Cancer Center, it adds to the evidence showing that the three-drug regimen is a more effective induction chemotherapy approach than the two-drug regimen. Among the limitations, she noted, was that the trial could not distinguish between patients with cancers of the larynx and hypopharynx. “This is important because the biology and natural history of these cancers is quite different despite their anatomic proximity,” she said.

Induction chemotherapy and simultaneous chemotherapy and radiation, called “concomitant chemoradiation,” have proven to be effective alternatives to surgery. Even with these results, Dr. Forastiere continued, it’s still not known whether induction chemotherapy is equivalent to, not as good as, or better than concomitant chemoradiation for preserving the larynx.

Obesity Worsens Survival after Pancreatic Cancer Surgery

Patients who are severely obese have a greater likelihood of lymph node metastases, disease recurrence, and decreased overall survival following pancreatic cancer surgery, reported a research team from the University of Texas M.D. Anderson Cancer Center. Published in the March 2009 Archives of Surgery, the single-institution study found that patients with a body-mass index (BMI) greater than 35 had a twofold greater risk of disease recurrence and death than patients with lower BMIs.

Noting that other studies have shown an association between similar BMI measurements and the risk of death from pancreatic cancer, Dr. Jason B. Fleming and colleagues said that the results of their new study “suggest that obesity is a host factor affecting tumor biology independent of the difficulties (patient- and treatment-related) involved in delivering oncologic care in obese patients.”

They looked at data from 285 consecutive patients who underwent surgery for pancreatic adenocarcinoma at M.D. Anderson between 1999 and 2006. Patients with a BMI greater than 35 had a median survival of 13.2 months, whereas patients with a BMI less than 23 had a median survival of 27.4 months. Nineteen of 20 patients with a BMI greater than 35 experienced disease recurrence at the last follow up, compared with 161 of the remaining 264 patients (95 percent versus 61 percent).

Patients with a BMI greater than 35 were less likely to receive radiation therapy before surgery than patients with lower BMIs, the team found, a complicating factor in assessing the risk of lymph node metastasis. Even so, after adjusting for that difference, there was a 12-fold greater incidence of lymph node metastasis in patients with a BMI greater than 35 compared with those with a lower BMI.

“To our knowledge,” they wrote, “the relationship between obesity and lymph node metastases observed in this study is the strongest reported in the literature to date, and it is supported by clinical and laboratory studies showing a relationship between obesity and cancer progression.”

In Talking about Prostate Cancer, Medical Language May Confuse Some Patients

Medical terms that physicians routinely use to discuss prostate cancer with patients, and that also appear in patient-education materials and research studies, are unfamiliar to many men with low literacy levels. This finding, reported in the Journal of Clinical Oncology on March 23, comes from interviews with more than 100 predominantly African American men at two low-income clinics in Virginia. The average patient was 58 years old and had a fifth-grade literacy level.

Fewer than half of the men understood the terms “erection” or “impotent,” and only 5 percent understood the term “incontinence”—words that are all commonly used to communicate the potential risks of prostate cancer treatments to patients. Many of the men were not familiar with basic aspects of human anatomy.

The researchers, led by Dr. Kerry Kilbridge of Massachusetts General Hospital, said that a limited understanding of prostate cancer terms and low literacy could be barriers to informed consent for treatment. In addition, the results of research studies, such as those assessing quality of life, may be inaccurate if participants lack an understanding of the questions.

The new findings could be used to improve communication about prostate cancer. The researchers created a table of synonymous colloquial terms for the common medical words used for prostate cancer. They urge caregivers not to assume that patients have a working knowledge of their internal anatomy and organ systems. “A safer place to start teaching prostate cancer is based on what a patient sees in the mirror,” they wrote.  

An accompanying commentary added, “Not only do we have to take heed in the language we use in communicating with patients in our clinical work, we must investigate rigorously whether the words contained in our study measures are actually understood by low-literacy populations.”

Rare Genetic Disorder Reveals How UV Exposure May Cause Melanoma

Much of what is known about how ultraviolet radiation (UV) causes skin cancer relates only to basal cell and squamous cell carcinoma. For melanoma, a less common but far more deadly form of the disease, there has been less evidence. New research suggests that UV-induced mutations in a gene called PTEN that normally suppresses tumors may play an important role in the formation of melanoma, according to findings published yesterday in the Proceedings of the National Academy of Sciences.

Researchers from NCI’s Center for Cancer Research and their collaborators at Brown University analyzed 59 melanoma samples taken from 8 patients with xeroderma pigmentosum (XP) who were seen at the NIH Clinical Center between 1971 and 2008. XP is a rare genetic disorder that compromises the ability of cells to repair DNA damage to the skin, putting these patients at a nearly 1,000-fold increased risk of melanoma, which progresses rapidly.

The researchers found that 56 percent of the XP melanomas analyzed harbored mutations in the PTEN gene. Of these mutations, 91 percent included DNA base substitutions of the type that usually result from UV damage, with between 1 and 4 changes per tumor. These mutations were also detected among melanomas in situ, those at the earliest stage of disease. Melanomas from the same person sometimes had different PTEN mutations, indicating that they arose independently.

The findings “provide a clear mechanistic framework for the role of UV in the induction of melanomas,” Dr. Kenneth Kraemer and colleagues wrote, “and a sound rationale for UV protective measures for melanoma prevention.”

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