Fight Colorectal Cancer

Tiny beads filled with a chemotherapy drug have reduced  the size of liver tumors and improved quality of life for people with advanced colorectal cancer.  Early results from  clinical trial comparing DC Beads therapy (DEBIRI) to FOLFIRI chemotherapy showed a significant difference in both tumor shrinkage and quality of life.

DC Bead microspheres — or drug-eluting beads — both close off tiny blood vessels feeding cancer tumors and deliver chemotherapy drugs directly to the tumors, killing cancer cells and shrinking tumors.  The beads are injected into an artery in the groin and travel through blood vessels to tumors that have spread to the liver.

Researchers in Italy treated 14 patients with DC Beads containing irinotecan (DEBIRI) and another 18 patients with FOLFIRI chemotherapy.  FOLFIRI is a combination of 5FU, leucovorin, and irinotecan and is injected into a vein. Patients in the trial had advanced colorectal cancer that had worsened with standard chemotherapy.

Response in the DEBIRI group was 80%, compared to only 10% for those who were treated with FOLFIRI.  After eight weeks of treatment, quality of life had improved by 70% for DEBIRI patients, while those on FOLFIRI had a 30% quality of life improvement.

Survival data is preliminary but also favors the DEBIRI arm. 

The cost per patient of the DEBIRI and FOLFIRI treatments was 4,000 euros and 12,000euros respectively.

A previous trial was reported during the 2007 ASCO annual meeting showing a similar response rate.  Side effects included abdominal pain which needed analgesia and fever.  At the time of reporting 22 of 25 patients were still alive with a median survival of 9.5 months.

The process that DC Beads using to treat liver tumors is called Trans-arterial chemoembolism (TACE).

At ASCO, Professor Giammaria Fiorentini said,

DC bead -TACE was feasible and effective in patients with liver metastases from colorectal cancer. Right upper-quadrant pain seems the most significant toxic event and needs analgesic therapy. No survival data are conclusive because the follow up is short. DC bead of IRI 100 mgr-TACE might be an appropriate palliative therapy for these patients.

Researchers in Sweden reviewed thirty studies relating obesity (body mass index) to colon or rectal cancer in both men and women.  They found differences between risks for men and women and whether the cancer was located in the colon or the rectum.

Men who were overweight had a greater increase in their risk than women for both colon and rectal cancer.  For colon cancer, obesity increase men’s risk by 30 percent, but women only had an 12 percent increase.

For rectal cancer, obese men had a 12 percent greater risk, but there was no similar increased risk for women.

For both men and women larger waist size increased colon cancer risk.  Again the risk was greater for men.

Susanna C Larsson and Alicja Wolk from the Karolinska Institute in Stockholm concluded:

The association between obesity and colon and rectal cancer risk varies by sex and cancer site.

SOURCE:  Larsson et al, American Journal of Clinical Nutrition, Volume  86, Number 3, pages 556-565, September 2007

Cancer patients who have a specific genetic type are at risk for serious — sometimes life-threatening — side effects when they are treated with Camptosar® (irinotecan).  The FDA-approved Camptosar label now calls for gene testing before beginning irinotecan treatment.

Previous studies have found about ten percent of patients will have a variation in the UGT1A1 gene that makes them particularly sensitive to irinotecan.

 However, researchers at the University of North Carolina reviewed nine studies in which irinotecan was given in high, medium, and low doses.  They found that although the genetic type UGT1A1*28/*28 increased risk of serious changes in blood counts at high and medium doses, at low doses side effects were similar in patients whether or not they had the special genotype.

Low doses of irinotecan (100–125 mg/m²) are commonly used for colorectal cancer treatment.

In a news release from the University of North Carolina,  Harold MacLeod, Pharm. D. said about the study’s implications,

Many institutions saw the FDA’s recommendation as a mandate to test all patients before treating them with irinotecan even though many clinicians didn’t think it was always necessary given that low doses of the drug weren’t causing problems

Our review showed that at low doses the drug is well tolerated and can be taken by most people. As the dosage increases, genetics become a larger factor in determining what side effects patients experience, and then testing becomes essential.

Richard M. Goldberg, MD added,

Having a genetic test available for a medicine is valuable, but so is knowing when to use that test.

There are so many treatment options for cancer patients that the more information we have about matching the right therapy to the patient, the better off we all are. Studies like this one give oncologists the tools needed to take better care of patients while avoiding tests and expenses that aren’t needed.

The study authors recommend that FDA labeling be changed to reflect the impact of irinotecan dose on side effects related to UGT1A1 genotype.

SOURCE: Hoskins et al, Journal of the National Cancer Institute, Volume 99, Number 17, 5 September 2007.

Merck Serano has announced that they are reconsidering developing matuzumab to treat metastatic colorectal cancer after a Phase II trial failed to show activity.  The trial combined matuzumab with irinotecan.

Patients enrolled in the trial had already had cancer get worse in other standard treatments, including irinotecan (Camptosar®).

Matuzumab is a fully humanized epidermal growth factor receptor inhibitor, blocking EGF receptors on tumor cells to keep cancer cells from dividing and tumors from growing.

Merck Serano will proceed with matuzumab clinical trials in other tumor types.

Hormone replacement therapy (HRT) reduces the risk of colorectal cancer, but does so at the price of increasing risk for breast cancer.

Researchers in Italy followed almost 74,000 women who had at least one prescription for hormone replacement therapy between 1998 and 2000.  By 2005, nearly 3,700 of those women had been hospitalized for cancer.

Italian women who used HRT for more than two years had 20 percent less risk of colorectal cancer than those whose use was less than six months.  However, longer term HRT use increased risk of breast cancer by 34 percent.

Hormone replacement therapy delivered via a skin patch reduced breast cancer risk somewhat.  Long term users of a transdermal HRT patch had a 30% increased risk of breast cancer while those women who took oral HRT more than doubled their chances of getting breast cancer.

G. Corrao and colleagues at the University of Milan concluded,

Evidence that long-term use of HRT is associated with increased risk of breast cancer and decreased risk of colorectal cancer is supplied from this study from a southern European population. Our findings indicate that transdermal therapy might have lower effect than oral therapy in increasing breast cancer risk.

SOURCE:  Corrao et al, Annals of Oncology, online advanced access, September 4, 2007.