Dr. Edith Mitchell

Last night, Dr. Edith Mitchell of Thomas Jefferson University Kimmel Cancer Center in Philadelphia, PA, updated colorectal cancer patients on the latest research and treatment news in an online webinar.

Dr. Mitchell highlighted the most important news for colon and rectal cancer patients to come from the 2011 Gastrointestinal Cancers Symposium held in San Francisco last month. She answer such questions as…

“Can doctors determine the chances that my cancer may return?”

“Can my doctors determine if I need chemotherapy?”

“Does Avastin or Erbitux benefit my stage III cancer treatment?”

“Are there any promising new treatments on the horizon?”

You can view the webinar online here.

The patient webinars are a program of the Colorectal Cancer Coalition and are offered to patients at no cost. If you would like to support this program through a financial donation, visit our Donate page.

Serious side effects were reduced when research radiologists used a special technique to target the most radiation on anal cancer tumors, while sparing nearby normal tissue.

Reported at the recent 2011 Gastrointestinal Cancers Symposium in San Francisco, intensity-modulated radiation therapy (IMRT) did not reduce overall side effects during chemotherapy and radiation treatment, but it did cut down on the most serious bladder, bowel, and skin problems.

At the same time, IMRT was a good as traditional external beam radiation in preventing local recurrences and the need for colostomies.  Survival after two years was also similar to a previous study that did not use the technique.

The study (RTOG-0529) enrolled 63 patients in a clinical trial in an attempt to find out if dose-painted IMRT could reduce side effects from chemoradiation treatment for anal cancer.  Study results were compared to a similar RTOG trial (RTOG-9811) that used external beam radiation more broadly over the entire pelvic region of 325 anal cancer patients.

The primary goal of RTOG-0529 was to reduce all moderate to severe side effects from chemoradiation compared to the earlier RTOG-9811.  While the trial failed to accomplish that goal, it did reduce the most severe side effects.

After six weeks, 64 percent of patients had their tumors respond completely.  This rose to 81 percent 12 weeks after treatment.

Side Effects

Toxic side effects are graded from 0 to 5, with 2 being moderate and 3 more serious.  The primary goal of the reported study was to reduce grade 2 and higher toxicity compared to the earlier external beam radiotherapy trial.  While that goal was not accomplished, grade 3 and higher toxicity from treatment was cut significantly.

Comparing  RTOG-0529 (IMRT) to RTOG- 9811 (external beam radiotherapy or EBR):

• Grade 3 plus skin toxicity was reduced from 50 percent with EBR to 20 percent using IMRT.
• Grade 2 plus effects on blood counts was reduced from 80 percent to 70 percent.  (Radiation affects bone marrow and blood counts.)
• Grade 3 plus bladder and gastrointestinal side effects were halved from 40 percent to 20 percent.
• Because side effects were easier to manage, patients spent less time in treatment:  a median of 43 days with IMRT compared to 49 days with the earlier regimen.

Treatment Outcomes

Comparing results of the two trials after two years:

• 19 percent of patients had cancer return locally in their pelvic region in both trials
• 8 percent of IMRT patients needed a colostomy compared to 11 percent in the earlier EBR study
• Survival with IMRT was 86 percent compared to 91 percent with EBR.
• Survival without any cancer was 77 percent versus 75 percent.
• Survival without needing a colostomy was 84 percent versus 83 percent.
• 14 percent of patients in the IMRT study developed distant metastases compared to 9 percent with EBR.

IMRT isn’t simple.  There is a fairly steep learning curve for radiation oncologists.  RTOG-0529 was designed with so that radiation therapy plans had to be reviewed by experts before treatment began.  Over 80 percent of those plans needed revision.  However, at the end of treatment, reviews showed that only three treatments had major problems focusing radiation accurately.

Anal cancer is different from colon or rectal cancer and is treated differently.  Radiation combined with chemotherapy (5-FU and mitomycin) is standard treatment.  When cancer cells remain after chemoradiation, surgery may be necessary that includes a colostomy.  In 2010 about 5,260 people were expected to be diagnosed with anal cancer with 720 deaths.

During a press briefing before the GI Cancers Symposium, Lisa Kachnic, MD, of Boston University, who led the study, said,

Dose-painting IMRT with 5-FU and mitomycin-C for anal canal cancer is associated with significant sparing of grade 3+ dermatologic and gastrointestinal acute toxicity without compromising two-year outcomes. Dose-painting IMRT is feasible with rigorous quality assurance and continued education.

SOURCE:  Kachnic et al., Two-year outcomes of RTOG 0529: A phase II evaluation of dose-painted IMRT in combination with 5-fluorouracil and mitomycin-C for the reduction of acute morbidity in carcinoma of the anal canal, 2011 GI Cancers Symposium, Abstract #368.

Dr. Kachnic discusses her conclusions during a presentation at the 2011 GI Cancers Symposium in San Francisco.

Researchers tried to push the envelope in treating rectal and anal cancer by adding new or different chemotherapy to standard chemoradiotherapy.  However, two trials in rectal cancer and one in anal cancer were not able to improve complete response rates for chemoradiation.  Adding extra chemotherapy after radiation was finished didn’t improve relapse-free survival for anal cancer either.

• The STAR trial from Italy found that adding oxaliplatin to chemoradiotherapy before rectal surgery did nothing to improve the rate of complete responses found at surgery.  There was also no decrease in the number of patients who needed a permanent colostomy.  Serious diarrhea was significantly worse in the oxaliplatin arm. However, unexpectedly, more distant metastases were found at the time of surgery among patients who didn’t get oxaliplatin (16 patients with spread to lungs, liver, or peritoneal surfaces vs only 2 who got oxaliplatin prior to surgery.)  Survival data is not yet available.
• In France, researchers in the ACCORD trial combined both an increase in radiation to 50Gy and the addition of oxaliplatin to standard treatment of 45Gy and capecitabine in an attempt to improve pathological complete response rates for chemoradiotherapy before rectal cancer surgery.  However, there was no significant impact on tumor response at surgery and no decrease in colostomies.  Serious diarrhea was significant worse (3 percent with no oxaliplatin, 13 percent in the increased radiation with oxaliplatin.)  They did show that Xeloda® (capecitabine) can be substituted for infusional 5-FU in chemoradiotherapy regimens.
• A large trial of anal cancer in the United Kingdom tried to improve both complete response to chemoradiation and disease-free and overall survival by using cisplatin instead of standard mitomycin-C during radiotherapy and by randomly giving two doses of cisplatin and 5-FU after radiation treatment ended.  Response to chemoradiation was excellent with 95 percent of patients having a complete response with either mitomycin-C or cisplatin.  Furthermore, maintenance chemotherapy didn’t change relapse-free survival at three years, with 75 percent of patients without recurrences whether or not they had the extra chemo.  The research team concluded that mitomycin-C remains standard treatment for anal cancer.