In some patients with colorectal cancer, the tumor is large enough to obstruct the colon or cause a bowel perforation.  Obstruction or bowel perforation can result in emergency admission to the hospital and are usually a sign of advanced cancer. Low-income women are at greater risk for being diagnosed with colorectal cancer after bowel obstruction, perforation, or an emergency hospital admission.

Researchers led by Dr. Linda Raubeneck in Toronto reviewed health data from 1997 through 2001 in Ontario for all patients diagnosed with colorectal cancer, looking specifically at those who also had a diagnosis of bowel obstruction or perforation or who were diagnosed during an emergency hospital admission (OPE).  During the time period about 41,000 people were diagnosed with colorectal cancer and 7,700 (19%) met the OPE criteria — obstruction, perforation or emergency admission.

Looking at risk factors that made OPE diagnosis more likely, Dr. Raubeneck’s team identified the following:

• Females
• Lower income
• Less likely to have had a colonoscopy or other bowel exam in the past five years
• Without a regular source of primary care
• Living in the urban Toronto area

A previous study by Dr. Raubeneck found that low income decreased the chances that an individual would have had a colonoscopy and that access to colonoscopy is better in rural than in urban areas of Ontario.

Expanding and targeting colorectal cancer screening programs are essential to reaching this group of women before cancer is advanced and cannot be successfully treated. 

In conclusion, she writes

Among persons with a new diagnosis of CRC in Ontario, women and those who are poor are more likely to present with obstruction, perforation, or emergency admission to hospital. Population-based CRC screening is needed to address these adverse outcomes.

Raubeneck et. al. American Journal of Gastroenterology Volume 101 Issue 5 Page 1098 Date May 2006:  Risk Factors for Obstruction, Perforation, or Emergency Admission at Presentation in Patients with Colorectal Cancer: A Population-Based Study

A detailed discussion of the Raubeneck study appears on Medscape.

INFORMATION FROM 2006 ASCO MEETING IN ATLANTA

Peripheral sensory neuropathy can be a serious side effect during treatment with some chemotherapies, including oxaliplatin which is now a standard therapy for both early stage and advanced colon cancer.

Lamotrigine or Lamictal is an anticonvulsant drug used to treat epilepsy.  Researchers randomized patients with severe painful peripheral neuropathy to 10 weeks of lamotrigine or placebo to assess its ability to reduce pain and other neurotoxicity from chemotherapy. Patients were being treated with vinca alkaloids, taxanes, platinum agents, or combinations of neurotoxic drugs.

Neither pain nor neuropathy scores were significantly different between the treatment group who received lamotrigine and the placebo group.  More lamotrigine patients (60%) discontinued therapy because of side effects than those on placebo (78%) and were less likely to complete all 10 weeks of therapy.

S.I. Renno and colleagues concluded:

These results suggest that lamotrigine is not effective for managing pain and symptoms due to CIPN.

ASCO 2006 Abstract 8530 — The efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: A phase III randomized, double blind, placebo-controlled NCCTG trial, N01C3.

peripheral sensory neuropathy

INFORMATION FROM THE 2006 ASCO MEETING IN ATLANTA

Although statistical chances for survival at 5 years are usually determined at the time of diagnosis, the reality is that prognosis improves the longer the patient lives.  Rather looking at the initial risk, conditional survival gives patients and their doctors a more realistic view of life expectancy after a cancer diagnosis. Conditional survival improves over time.

Statisticians at the National Surgical Adjuvant Breast and Bowel Project examined survival curves for patients in NSABP colon cancer clinical trials to determine how conditional survival improved as patients survived in the years past initial diagnosis.  They analyzed survival information for nearly 5,600 patients who had received treatment with 5FU in one of several clinical trials.  Patients in these trials all were initially diagnosed with either stage II or III colon cancer.

They found that as the number of years since diagnosis increased without cancer recurring statistical chance of survival increased.  At diagnosis the patients studied had a 76% chance survival risk; after 5 years that percentage had increased to 85%.  For Stage III patients a 68% risk increased to 88% after 5 years.

Prognostic factors, such as number of positive lymph nodes or stage, that reduced survival risk at diagnosis had almost no significance at 5 years.  Patients who were older or had poor performance status unfortunately did not experience a reduction in risk as they continued to live past diagnosis.

In the NSABP study, stage II patients had an 87% chance of overall survival at diagnosis.  This remained at 87% after 1 year and increased to 90% at 2 years, 92% at 3 years, 91% at 4 years and, 92% at 5 years.  Stage III patients had a 68% survival risk at diagnosis which increased to 72% at 1 year, 81% at 2 years, 87% at 3, 89% at 4, and 88% at 5 years.

In considering this data, is is important to remember that an older treatment was used that did not contain the standard oxaliplatin, that all patients received some form of 5FU, and that the patients were enrolled in clinical trials.  So the statistics may not translate to the general population today, although the principles behind conditional survival probably do — the longer a patient lives past diagnosis, the better the chance for disease-free survival.

Samuel Wang, M.D. Ph.D. presented the data.

An additional article about the study appears in Science Daily, June 7, 2006.

ASCO 2006 Abstract 6005 —  Conditional survival for patients with colon cancer: An analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) trials C-03 through C-06.

 conditional survival

INFORMATION FROM 2006 ASCO MEETING IN ATLANTA

Patients can safely be treated intermittently with FOLFIRI (irinotecan, leucovorin, and continuous infusion 5FU) with no negative effect on overall survival according to a study presented at the meeting of the American Society for Clinical Oncology in Atlanta. 

Italian researchers, headed by Dr. Roberto Labianca compared two strategies for administering FOLFIRI to patients with advanced colorectal cancer who had not yet received chemotherapy for their metastatic cancer.

• ARM A: Two months of FOLFIRI (irinotecan, leucovorin, and infusional 5FU) followed by a two month “vacation” followed by a 2 month resumption of FOLFIRI.  Four month cycles of vacations and treatment were repeated until tumor progression when patients changed to a second line regimen with oxaliplatin.
• ARM B: Standard FOLFIRI treatment given every two weeks until tumors progressed.  After progression, patients moved to second-line treatment with oxaliplatin.

Results were similar in both arms of the trial:

• Response rate was 29% in intermittent arm A and 35% in arm B where treatment was continuous.
• Time to tumor progression was 8.8 months in A versus 7.3 months in B.
• At a median follow-up time of 27 months, median overall survival was 16.9 months (A) versus 17.6 months (B).  This is not the final analysis, but survival curves are almost identical at this point.
• The worst toxicity experienced by patients was also similar in both arms.

The research team concluded:

Our results demonstrate that alternatiing FOLFIRI obtains the same survival as continuous treatment, thus reducing the discomfort to patients and the economic costs.

ASCO 2006 Abstract 3505 — Alternating versus continuous “FOLFIRI” in advanced colorectal cancer (ACC): A randomized “GISCAD” trial.

FOLFIRI intermittent chemotherapy

INFORMATION FROM 2006 ASCO MEETING IN ATLANTA

Patients with metastatic can have time off entirely from chemotherapy for metastatic colorectal cancer without sacrificing effectiveness according to the OPTIMOX2 study presented at the American Society of Clinical Oncology meeting in Atlanta.

Oxaliplatin in the FOLFOX chemo regimen can cause tingling, numbness, pain, and other neurological problems in the hands and feet as doses accumulate.  Sometimes patients who are still responding to treatment have to stop because of this neuropathy. Strategies to reduce the amount of oxaliplatin received during treatment.can reduce neuropathy, allow therapy to continue, and improve quality of life.  A previous study — OPTIMOX1  — used a Stop-and-Go strategy to administer FOLFOX for patients newly diagnosed with advanced colorectal cancer.

• Give 6 treatments with FOLFOX4, a combination of oxaliplatin, leucovorin, and infusional 5FU.
• Stop oxaliplatin and continue with 12  maintenance doses of infusional 5FU with leucovorin.
• Begin FOLFOX7, including oxaliplatin, again and continue until tumors progress.

When the OPTIMOX1 intermittent strategy was compared to standard FOLFOX treatment patients had no significant difference in response rate (58.5% for OPTIMOX1 versus 58.3% for traditional FOLFOX), progression-free survival (9 months vs. 9.2 months), and overall survival (20.0 vs 20.6 months).  Fewer patients had severe neurotoxicity in the Stop-and-Go arm (13.3%) compared to the standard approach (18.7%).

OPTIMOX2 sought to find out whether the maintenance treatment could be eliminated completely, giving patients a break from chemotherapy until their cancer began to grow worse.  The study compared two approaches.

• The intermittent Stop-and-Go regimen used in OPTIMOX1 with slight changes in dosages.
• A similar regimen beginning with FOLFOX7 treatments but then moving to a chemotherapy free interval (CFI) until tumor progression. Treatment with FOLFOX resumed when tumors began growing again.  However,chemotherapy was not started until tumors reached the size they were at the very beginning of treatment, further extending the CFI for those patients whose cancer responded to the initial therapy.

Two hundred patients were enrolled in the study, half in each arm.  Results available at the time of the ASCO presentation:

• Duration of disease control (total time of progression free survival before and after the maintenance phase) was the same in both arms of the study. 
• It is too soon to know whether overall survival times will also be the same.
• Overall, patients on the OPTIMOX2 arm had a median 4.6 months without any chemo.  Those with good prognostic factors did even better with  median 8 months until tumors progressed for the second time and they resumed FOLFOX chemotherapy.
• Twelve patients in each arm had tumors reduced enough to have them surgically removed.

Dr. Frederique Maindrault-Goebel presented the results of the trial for the GERCOR team.  Concluding her presentation, she said,

“We believe that we can safely stop modified FOLFOX7 after only 6 cycles, especially in patients with response or stabilization and no negative prognostic factors.”

ASCO 2006 Abstract 3504 — OPTIMOX2, a large randomized phase II study of maintenance therapy or chemotherapy-free intervals (CFI) after FOLFOX in patients with metastatic colorectal cancer (MRC). A GERCOR study.

chemotherapy free interval FOLFOX