A prospective randomized study in 393 early-stage prostate cancer patients has found that increasing the energy delivered during primary radiotherapy from the conventional dose of 70 Gy to 79.2 Gy results in a 49 percent reduction in the risk of increased PSA levels. The finding is "pivotal," said an accompanying editorial in the September 14 Journal of the American Medical Association, because it "provides support for dose escalation in men with lower-risk disease."
Researchers followed the men for 5.5 years, looking primarily at PSA levels. Biochemical recurrence of the cancer was diagnosed in 38.6 percent of those who had been treated with 70 Gy, compared with 19.6 percent who had received 79.2 Gy. While this result mirrors other studies, a subset of 227 men whose clinical findings at diagnosis put them at lowest risk also fared significantly better with the higher dose: Only 19.5 percent relapsed, compared with 39.9 percent who received the conventional dose.
Lead author Dr. Anthony L. Zietman of Harvard Medical School and colleagues emphasized that the advantage of high-dose radiation for low-risk patients must be balanced against the possibility of increased side effects such as rectal bleeding. Such increases in this study were seen only at the Grade 2 level.
The editorial noted the general trend toward higher radiation in the last two decades, which has been made safer by more precise three-dimensional conformal therapy techniques that shape the radiation to minimize damage to surrounding and intervening tissue.
The editorial also noted that while this study used an advanced proton-beam radiation delivery system, the effect on tissue is comparable to standard photon radiation.
The inactivation of a specific gene by a process called DNA methylation may be a marker by which to detect or assess the risk of developing sporadic colorectal cancer, according to a new study. The study, led by researchers from the University of Texas M.D. Anderson Cancer Center, focused on whether DNA methylation of the MGMT gene, which repairs damaged DNA, is a marker for a "field defect" (a region of unstable, potentially precancerous cells) in colon tissues that predisposes people to colon cancer.
Previous research has linked methylation of MGMT to mutations of the KRAS gene, which is thought to play an important role in colon cancer development. In a study published in the September 21 Journal of the National Cancer Institute (JNCI), Dr. Jean-Pierre Issa and colleagues used several different methods to assess MGMT promoter methylation in samples from colon cancer tumors and in the adjacent or nearby mucosa in 95 patients. They also analyzed colon tissue samples of 33 people without colon cancer.
More than 45 percent of tumor samples had MGMT promoter methylation. Depending on the method used, anywhere from 50 to 94 percent of adjacent cells demonstrated DNA methylation, as did 10 of the 13 available nonadjacent samples. Methylation of MGMT was also detected in the normal colon mucosa from several healthy participants. The study results, the researchers argue, point to the possibility of conducting clinical trials using MGMT promoter methylation as a "marker of risk" of colon cancer.
An editorial notes that DNA methylation-related field defects raise important questions about testing chemopreventive agents - such as folate for colon cancer prevention - in that such agents could have varied effects depending on the presence of a field defect.
Beta-carotene supplements have been found to increase lung cancer risk in males who smoke. New results from a large prospective observational cohort study in the September 21 JNCI extend this finding to women - and to other tobacco-related cancers.
Women in the study who were current or ever-smokers who took beta-carotene at the high levels found in supplements more than doubled their risk of tobacco-related cancers, compared with women getting the lower amounts found naturally in certain foods (3.1 mg/day or less). In contrast, among those who had never smoked, the relationship was reversed: Those taking high levels of beta-carotene as a supplement cut their risk by 56 percent compared with those taking the smaller amount.
The study known as E3N is the French component of the European Prospective Investigation into Cancer and Nutrition. Lead author Dr. Marie-Christine Boutron-Ruault, of INSERM in Villejuif, France, and colleagues collected questionnaires about beta-carotene consumption from 59,910 women who enrolled in the prospective study, which began in 1990. During a median follow-up of 7.4 years, 700 women developed tobacco-related cancers. From most to least frequent incidence, these included colorectal, thyroid, ovarian, cervical, lung, urinary tract, pancreatic, head-and-neck, stomach, anal, and liver cancer.
In an accompanying editorial, Dr. Susan T. Mayne of the Yale University School of Medicine and Dr. Scott M. Lippman of the University of Texas M.D. Anderson Cancer Center observed that "Evidence suggesting tobacco exposure modifies the chemo-preventive efficacy of nutrients/nutrient derivatives continues to mount."
The targeted drug erlotinib (Tarceva) showed promising activity and tolerable toxicity as a first-line treatment for elderly patients with advanced, non-small-cell lung cancer (NSCLC), according to a phase II study reported last week at the European Respiratory Society Annual Congress in Copenhagen, Denmark.
The single-center study included 80 NSCLC patients aged 70 and older (median 75 years) who had never undergone chemotherapy, and most (69 percent) had not had other treatments, such as surgery or radiation. The researchers at Dana-Farber Cancer Institute reported a median survival time of 46 weeks among the patients.
Although none of the patients had complete responses to erlotinib, 60 percent had either partial responses (median duration 65 weeks) or stable disease (median duration 24 weeks).
In addition, the drug was well tolerated by most patients, with rashes and diarrhea being the most common side effects. Ten patients were discontinued from the study due to toxicity and there was one treatment-related death due to pneumonitis.
Current chemotherapy for older patients with advanced NSCLC is associated with some survival benefits but also significant toxicity, the researchers noted. Dana-Farber's Dr. Bruce Johnson, who headed the research, commented, "While further research is needed, our findings suggest that it may be beneficial to use erlotinib - a relatively non-toxic targeted agent - to initially treat patients with advanced lung cancer, rather than use conventional chemotherapy regimens."
The investigators recommended that a larger phase III trial be considered for this population to compare first-line erlotinib against single agent vinorelbine (Navelbine). Erlotinib is already approved as a second-line therapy for NSCLC after chemotherapy has failed.