Re: [MOL] Colon/liver tumors/Medicare and drug status quo/trials/fda cle [00677]

Another Blow for Diet and Colon Cancer

DIJON, France--The role of dietary fiber in the prevention of colorectal cancer may be down for the count.

Less than six months after two randomized U.S. trials dashed the hopes of many in the cancer establishment that a high-fiber diet would retard the recurrence of adenomatous polyps, a European study of dietary-fiber supplements strongly reinforced the negative findings.

Coincidentally, the FDA ruled on Oct. 11 in Washington that health claims relating to dietary-fiber supplements and a reduced risk of colorectal cancer are inherently misleading. What’s more, said the FDA, the claims cannot be made non-misleading with a disclaimer or other qualifying language.

The FDA action followed a federal appeals court order in a suit brought by a Nevada maker of dietary supplements and others. The court instructed the agency to review a 1993 decision that disallowed claims of a direct association between a reduced risk of colorectal cancer and diets high in fiber. Lawyers for the plaintiffs characterized the latest FDA move as a setback.

The agency study stuck to its 1993 approval of health claims that link a reduced risk of colorectal cancer and a low-fat diet of fiber-containing grain products, fruits, and vegetables. This approved association did not include fiber per se or fiber supplements.

The results of the European placebo-controlled study found more colorectal adenoma recurrence after three years in the arm randomized to a daily supplement of ispaghula husk, a soluble fiber, than among those randomized to a daily calcium supplement or among the controls. Ispaghula husk was chosen because it has stool-bulking

properties.

In all, at least one adenoma developed in 58 of the 198 (29.3%) in the fiber-supplement group, 28 of the 176 (15.9%) in the calcium-supplement group, and 36 of 178 (20.2%) of the controls, Dr. Claire Bonithon-Kopp of the University of Bourgogne here reported in the Oct. 14 Lancet along with Italian, German, and Danish colleagues.

They were reporting for the 10-nation, 21-center European Cancer Prevention Organization Study Group. They said the adverse effect of 3.5 g/day of fiber supplement was significant, but the beneficial effect of 2 g/day of calcium wasn’t. Participants were assessed by colonoscopy.

In both the U.S. trials, published in the New England Journal of Medicine in April, three years of intervention with high-fiber, low-fat diets yielded no difference in polyp recurrence over groups randomized to standard advice.

For Inoperative Liver Tumors RF Ablation Blazes a Trail

HOUSTON--Radiofrequency ablation appears to be successfully burning away localized inoperable liver cancer.

After an average follow-up of 19 months, 56 of 110 patients with cirrhosis and unresectable hepatocellular carcinoma treated with RF ablation had no evidence of recurrence, says a team at the M.D.

Anderson Cancer Center here. The 110 patients had 149 tumors. Seventy-six patients with smaller tumors (average diameter 2.8 cm) were treated percutaneously, reported Dr. Steven A. Curley and colleagues in the September Annals of Surgery. Larger tumors (average 4.6 cm) in 34 patients were ablated intraoperatively, 31 via laparotomy and three laparoscopically.

Four patients had a local recurrence during follow-up and 50 developed new liver tumors or tumors elsewhere in the body. A second ablation was performed for solitary liver recurrences in 14 patients.

There were no deaths associated with the RF treatment, but 14 patients (12.7%) developed complications that included delayed bleeding into the tumor, hematoma, hemorrhage from incision, liver insufficiency, pleural effusion, ventricular fibrillation, and fever.

The M.D. Anderson team does not recommend the procedure for tumors larger than 5 or 6 cm.

Legislation Would Keep Drug Status Quo

WASHINGTON--Congress moved rapidly this week toward nailing the door shut for perhaps a year or more on any changes in the current formula for Medicare reimbusement of cancer drugs.

The expected congressional actions would give full victory to ASCO after HCFA backed off plans to reduce chemotherapy-drug reimbursement for Medicare patients from 95% of average wholesale prices to 67%.

Conceding that oncologists had a point in their summer-long cries of discontent, HCFA said it would study the issue, with the idea of adjusting cancer-drug reimbursement down and bringing oncologists’ practice-expense relative-value rates up.

Now Congress is formalizing HCFA’s promises. Legislation expected to be passed within days would prevent any reductions in Medicare drug payments until after a GAO study assessed both the HCFA payments and the practice-expense RVS for chemotherapy administration. There may also be a study of the difference between average wholesale price and average acquisition costs. A year’s moratorium by Congress on any HCFA changes seemed likely.

Dr. Larry Norton of Memorial Sloan-Kettering Cancer Center, the society’s president-elect, said ASCO wants to work to refine the system to make sure it’s equitable for oncologists.

In a letter to HCFA, Dr. Joseph S. Bailes of U.S. Oncology, the society’s immediate past president, emphasized the need to adjust not only the payment amounts for chemotherapy admin-istration services but also the payment amounts for the infusion and injection of nonchemotherapy drugs.

The latter, he said, cover the costs of giving antiemetics, fluids, and other drugs that are used in cancer chemotherapy but aren’t anticancer agents. "We believe that HCFA’s review of the payments for these services will show that they are underpaid in the same manner as the analogous codes for administration of chemotherapy drugs," said Dr. Bailes.

Too Depressed for Chemotherapy?

MILAN--Depressed women with breast cancer seem less likely to accept adjuvant chemotherapy than other breast-cancer patients.

Only 20 of 39 breast-cancer patients who’d requested psychological support and fit the DSM-IV criteria for depression had a recommended course of chemotherapy after surgery, according to a study here by the European Institute of Oncology. This compared with 75 of 78 patients without depression.

Five of the depressed patients who refused treatment eventually accepted a lower-dose regimen, Dr. Marco Colleoni and colleagues reported in the Oct. 14 Lancet. They said that all of the other patients who received chemotherapy accepted the regimen unchanged.

Women in the control group, recruited from the European Institute of Oncology database, were matched with the depressed patients for age, performance status, and type of surgery. However, the researchers did not assess the depression status of women in this group.

In the Pipeline...

Enrollment full for Maxamine trials

Maxim Pharmaceuticals of San Diego has completed enrollment in two phase-3 trials of histamine dihydrochloride (Maxamine). An AML trial is for Maxamine in combination with IL-2, after phase-2 trials found that this combination prevented relapse and extended remission. An advanced metastatic melanoma trial is comparing Maxamine, low-dose IL-2, and interfereon-a with dacarbazine. Maxamine is said to enhance the effectiveness of IL-2 and other cytokines by reversing immune suppression. Earlier, the company applied for FDA approval of Maxamine as an adjuvant to IL-2 for advanced metastatic melanoma.

Lipid-based IL-2 trial at halfway mark

Valentis of Burlingame, Calif., announced this week that it has reached the halfway point of enrollment of its phase-2b trial of a lipid-based IL-2 gene delivery system for head-and-neck cancer. Forty patients with inoperable head-and-neck cancer are receiving the gene along with chemotherapy, with few adverse responses. The company is testing this delivery system in two other trials, and it believes that the system can induce a superior local and systemic antitumor response.

Glioblastoma agent gets orphan status

Ethypharm of Paris has received orphan-drug status from the FDA for 5-FU biodegradable implantable microspheres for glioblastoma. The microspheres, implanted in tumors, release 5-FU continuously for 30 days. Clinical trials are under way, and the company says it has set a 2002 target for availability.

Peregrine is cleared

Nomos Corporation of Sewickley, Pa., has received FDA clearance for Peregrine radiation treatment technology. Peregrine, developed by the Department of Energy and UC San Francisco at the Lawrence Livermore National Laboratory, is a dose-calculating system that creates 3-D computer models of tumors and simulated particle interaction. The system depicts how radiation is absorbed, including areas absorbing more than others. The company says this will allow higher doses of precisely targeted radiation. Initially, the technology will be available only as part of Nomos’ CORVUS treatment-planning system.

PrecisePlan is okayed

Elekta of West Sussex, England, has received FDA approval for PrecisePlan, a system for radiotherapy planning. The company says the system uses 3-D spatial referencing to position tumors for optimal

radiotherapy.

Re: [MOL] Colon/liver tumors/Medicare and drug status quo/trials/fda clears/