Folic Acid Study Shows Surprising Results

A study that set out to test folate for prevention of early-stage colon cancer instead found a higher incidence of colorectal adenomas in the test group. This multi-institutional NCI-funded research, performed by the Polyp Prevention Study Group, appeared in the June 6 Journal of the American Medical Association.

The cohort included 987 people who had a history of colorectal adenomas, precursor lesions for cancer. Half of these people received 1 mg/day of folic acid and the other half received a placebo. The average person gets about 0.2 - 0.4 mg of daily folate in their diet. Participants were monitored with colonoscopies after 3 and 5 years.

With an average follow-up of 3 years, colorectal adenomas occurred in 42.4 percent of participants who received the placebo and in 44.1 percent of those who received folic acid. At the 5-year follow-up, participants in the folic acid group also had higher rates of advanced lesions and greater numbers of lesions than the control group.

An accompanying editorial speculates that the most likely explanation for this increase in advanced lesions (known precursors to colorectal cancer) is that they are promoted by increased folate.

The editorial also notes that a history of colorectal adenomas was a prerequisite for inclusion in the study, and the endpoint was whether additional adenomas formed, not whether cancer was prevented in this high-risk group. "The question of efficacy of folate in cancer prevention is not resolved…Animal experiments showing chemopreventive effects of folate, as well as the strong observational epidemiological evidence, speak to [its] potential…if taken early," the editorialists wrote.

Meta-Analysis Suggests Cisplatin Superior to Carboplatin for Advanced NSCLC

Cisplatin is likely a better option than carboplatin for patients with advanced-stage non-small-cell lung cancer (NSCLC), according to a meta-analysis of nine randomized clinical trials comparing the two drugs.

The analysis, which involved data on nearly 3,000 individual patients, revealed a superior response rate in patients with NSCLC treated with a cisplatin-based chemotherapy regimen compared with carboplatin-based regimens, and a small but statistically significant improvement in overall survival in patients with nonsquamous NSCLC and those in whom cisplatin was combined with so-called third-generation chemotherapy drugs, such as gemcitabine, paclitaxel, and docetaxel.

"The superiority of cisplatin over carboplatin was not achieved at the cost of a statistically significant increase in the incidence of severe side effects," wrote lead author Dr. Andrea Ardizzoni, of University Hospital in Parma, Italy, and colleagues in the June 6 Journal of the National Cancer Institute (JNCI). They reported that, while cisplatin-based regimens were associated with a greater incidence of high-grade nausea, vomiting, and kidney problems, carboplatin was associated with more drastic drops in platelet counts (thrombocytopenia).

Based on clinical trial results, the two drugs have been considered to be equally effective in treating advanced NSCLC, and U.S. oncologists have favored carboplatin because it has been associated with fewer side effects and is easier to administer.

In an accompanying editorial in JNCI, Dr. Christopher G. Azzoli, from Memorial Sloan-Kettering Cancer Center, and colleagues noted that more effective antinausea medications could help to decrease cisplatin's toxicity burden. They also cited cisplatin's increased effectiveness in patients with nonsquamous disease, which they argued was particularly important given the success seen in a recent U.S. phase III study in the same patient population treated with a combination of the targeted agent bevacizumab (Avastin) and carboplatin and paclitaxel.

Overall, the editorial states, "the apparent superiority of cisplatin over carboplatin…should not be taken lightly, particularly in patients being treated with a curative intent."