Combination versus sequential chemotherapy for advanced colorectal cancer

Now that there are several effective drugs to treat advanced colon and rectal cancer,  is it better to give several at once in combination or one after the other in sequence? 

The current issue of The Lancet has reports of two large randomized trials to compare overall survival and serious side effects of sequences of chemotherapy versus combination strategies.  The CAIRO  trial tested strategies with oral capecitabine (Xeloda®), irinotecan (Camptosar®),and oxaliplatin (Eloxatin®).  The FOCUS trial studied continuous infusion 5FU (fluorouracil), irinotecan, and oxaliplatin.

Neither trial included biologic agents bevacizumab (Avastin®), cetuximab (Erbitux®), or panitumumab (Vectibix®) which have become part of standard treatment for metastatic colorectal cancer.

A comment  in The Lancet considers whether or not this new information should prompt a change in standard chemotherapy regimens in the United States and Europe.

In the Netherlands CAIRO trial, 820 patient who had not been previously treated for metastatic colorectal cancer were randomized to receive either:

• Sequential strategy:  (First) single drug capecitabine, (Second) single drug irinotecan, (Third) combination of oxaliplatin and capecitabine (CAPOX).
• Combination strategy:  (First)combination of capecitabine and irinotecan (CAPIRI) followed by (Second) combination of capecitabine and oxaliplatin (CAPOX).

In both strategies, patients remained on each regimen until their cancer progressed and then moved to the next line of treatment.

There was no significant difference in overall survival in the CAIRO trial between the two groups.  Median overall survival for the sequential strategy was 16.3 months; for the combination strategy 17.4 months.  There was more serious hand-foot syndrome in the sequential arm (13 percent versus 7 percent for the combination arm.)

The FOCUS trial, conducted in the United Kingdom, used continuous infusion 5FU rather than oral capecitabine.  2135 patients were randomized to one of three strategies:

• A:  Continuous infusion 5FU with leucovorin followed by single agent irinotecan.
• B:  Continuous infusion 5FU followed by either 5FU plus irinotecan (FOLFIRI) or 5FU plus oxaliplatin (FOLFOX)
• C: Either FOLFIRI or FOLFOX from the beginning of treatment.

Median survival for the A strategy that used two single drugs was 13.9 months,  not as good as either B or C.  For B, median survival was 15.0 months for FOLFIRI and 15.2 months for FOLFOX.

When combinations were given from the beginning, median survival for the FOLFIRI group was 16.7 months compared to 15.4 months for FOLFOX.  Statistically, using the combination FOLFIRI strategy for first-line treatment was superior to other treatment approaches.

Writing for the CAIRO trial, lead author Miriam Koopman MD, concluded,

Our results show that, for patients with advanced colorectal cancer, combination treatment with all effective cytotoxic drugs was no better than their sequential use. Progression-free survival over all subsequent treatment lines was not significantly different between the study groups. Additionally, sequential treatment was associated with less toxicity during first-line treatment than was combination therapy.

For the FOCUS trial, Matthew T. Seymour MD and his colleagues wrote,

Our data challenge the assumption that, in this non-curative setting, maximum tolerable treatment must necessarily be used first-line. The staged approach of initial single-agent treatment upgraded to combination when required is not worse than first-line combination, and is an alternative option for discussion with patients.

Comments from Hans-Joachim Schmoll and Daniel Sargent on the meaning of these two trials and their impact on patient decision-making will be discussed in a subsequent C3 News and Events post.

SOURCE 

For CAIRO trial:  Koopman et. al.The Lancet, Volume 370, Number 9582, July 14, 2007.

For FOCUS trial:  Seymour et. al. The Lancet, Volume 370, Number 9582, July 14, 2007

Posted by Kate Murphy on July 15th, 2007
Posted in: Research & Treatment News | 1 Comment »

Subcommittee Allocates FY08 Funds to FDA

Yesterday the House of Representatives’ Agriculture Appropriations
Subcommittee marked up its Fiscal Year 2008 Appropriations bill. The appropriations bill allocates funds to the Food and Drug Administration. Chairwoman Rosa DeLauro (D-CT) stated that she recognized there is a resource problem at the FDA and made a commitment to multi-year funding.

The FDA is funded at $1.7 billion, $121.5 million (7.7%) above Fiscal Year 2007 and $55 million (3.4%) above the President’s budget request.

Though not as high as hoped for, this is the best FDA budget in recent years.

Posted by Joe Arite on July 13th, 2007
Posted in: Policy & Advocacy News | No Comments »

NCI wants to interview women caring for people with cancer

The National Cancer Institute and the George Washington School of Public Health want to talk to women who are caring for a family member or friend with cancer.   They want to learn more about the caregiving experiences and how caregivers cope.

The study wants to reach

• Women
• Between the ages of 31 and 80
• Currently providing care for someone over the age of 20 with cancer, OR
• Provided care for someone over the age of 20 with cancer at end-of-life within the last year

Study participation involves a 15-20 minute telephone interview.  Some eligible caregivers will be asked to provide additional information about their experience during a follow-up 45-60 minute phone call.

To participate call

• 1-888-249-0029
• Monday to Friday, 9am-5pm EDT

Posted by Kate Murphy on July 11th, 2007
Posted in: Research & Treatment News | 1 Comment »

FDA rejects health claims that tomatoes and lycopene reduce cancer risk

The United States Food and Drug Administration has refused to allow health claims that tomatoes or lycopene reduce the risk of getting cancer.  For such claims to appear on the labels of food products or dietary supplements, the FDA must approve them before they are marketed. 

According to a review in the Journal of the National Cancer Institute, the FDA found

• No credible evidence that there was an association between lycopene intake and a reduced risk of prostate, lung, colorectal, gastric, breast, ovarian, endometrial, or pancreatic cancer.
• No credible evidence for an association between tomato consumption and a reduced risk of lung, colorectal, breast, cervical, or endometrial cancer
• Very limited evidence to support an association between tomato consumption and reduced risks of prostate, ovarian, gastric, and pancreatic cancers.

In 2004 the FDA received two petitions for qualified health claims supporting the association between tomatoes, lycopene, and the risk of certain cancers.

In an accompanying editorial, Paul M. Coates from the Office of Dietary Supplements at the National Institutes of Health points out the difficulties of finding strong evidence to support tomato and lycopene claims.  Many studies were preclinical, small, or based on observation.  However, he defends the importance of clear and transparent evidence-based reviews and points out that such reviews can be updated if new information becomes available.

A second editorial writer, Edward Giovannucci, from the Department of Nutrition at the Harvard School of Public Health points out that studies supporting an association between tomato sauce, lycopene, and prostate cancer were done before PSA testing became common in the United States.  More recent studies don’t agree.  However, he believes that there may be a connection between more advanced prostate cancer and tomatoes that should be studied further, along with possible genetic associations and combinations of tomatoes, lycopene and other antioxidants.

More information is available in a JCNI press release.

SOURCE: Kavanaugh et. al, Journal of the National Cancer Institute, advance access, July 10, 2007.

Posted by Kate Murphy on July 11th, 2007
Posted in: Research & Treatment News | No Comments »

Weighing complications and survival in treating pelvic recurrences of rectal cancer

Even after successful surgery to remove rectal cancer, pelvic recurrences can happen.  Surgery to remove the cancer offers a possibility of cure, but also has risks.

Surgical oncologists at Fox Chase Cancer Center in Philadelphia retrospectively reviewed surgeries to remove pelvic recurrences after rectal cancer surgery from 1988 through 2003 where the goal was curing the cancer. 

Studying outcomes for 90 patients, they found

• 4 (4.4%) died during surgery
• 53 percent had surgical complications
• 5-year survival rate was 40%
• 51 of 86 patients had another recurrence: 15 locally, 16 to distant organs, and 20 both locally and distant

Carcinoembryonic antigen level (CEA) before surgery and clear surgical margins helped predict successful treatment.

Writing in the Annals of Surgical Oncology, Leonard B. Henry, MD, concluded,

The resection of pelvic recurrences after colorectal surgery for cancer can be performed with low mortality and good long-term outcome; however, morbidity from such procedures is high. Low preoperative carcinoembryonic antigen and negative margin of resection predict improved survival.

SOURCE: Henry et. al. Annals of Surgical Oncology, Volume 14, Issue 7, July 2007.

Posted by Kate Murphy on July 9th, 2007
Posted in: Research & Treatment News | No Comments »