Listen to interviews with oncologists and patients at Cancer Questions and Answers to get some real-world perspective on issues such as:

• What is adjuvant therapy and why might I need it?
• What are the common side effects of the most common chemotherapy?
• What will life be like when adjuvant therapy is over?

The interviews can be read or listened to online, and can be downloaded to MP3 players.

Participating oncologists include:

• George Fisher MD PhD, Stanford University
• Axel Grothey* MD, Mayo Clinic
• John Marshall* MD, Lombard Cancer Center
• Neal Meropol* MD, Fox Chase Cancer Center
• Leonard Saltz MD, Memorial Sloan Kettering Cancer Center
• Robert Wolff MD, MD Anderson Cancer Center

* Member of C3 Medical Review Network

This website was developed by Research to Practice, a medical education company headed by Dr. Neil Love.

By Andy Giusti, Ph. D, C3 Research Program Manager

A phase IV clinical trial designed to test if calcium/magnesium infusions lessened neuropathy when administered with Eloxatin (oxaliplatin) as part of the common FOLFOX+Avastin chemotherapeutic regimen has been closed. The manufacturer of Eloxatin, Sanofi-Aventis has stopped the trial after an interim analysis indicated that the use of calcium/magnesium could reduce the effectiveness of this chemotherapy treatment.

Read the text of the alert here in PDF format.

This study compared the use of calcium/magnesium infusions vs. placebo in previously untreated colorectal cancer patients receiving FOLFOX+ Avastin. The objective of the study was to determine if the addition of calcium/magnesium would reduce the severity or incidence of neuropathy, a commonly observed side effect in patients that are receiving Eloxatin as part of their chemotherapy treatments.

The trial was stopped while Sanofi-Aventis performs a more complete analysis of their data. It should be noted that this was not a safety issue with Eloxatin, but rather an issue of reduced efficacy when using calcium/magnesium in an attempt to lessen the side effects of Eloxatin treatment.

Until this analysis is made available, patients should carefully weigh the supposed benefit of decreased neuropathy that may be obtained when using calcium/magnesium, with the potentially more serious prospect of reduced effectiveness of their chemotherapy treatment.

Disclosure: C3 has accepted funding for projects and educational programs from Sanofi-Aventis in the form of charitable donations. C3 has ultimate authority over website content.

NEWS FROM ASCO 2007

Chemotherapy given before and after surgery to remove colorectal cancer tumors that have spread to the liver significantly improves three-year progression-free survival.

Results of a randomized phase III clinical trial were discussed at the 2007 ASCO annual meeting in Chicago.  Patients who had cancer that had spread to their liver  considered surgically removable by their doctors either had surgery to remove the liver tumors right away or were assigned to a chemotherapy group.

Patients in the trial had four or fewer liver metastases and had no other cancer outside their livers. 

The chemotherapy group received 6 FOLFOX4 treatments before surgery and 6 treatments afterwards.

After three years there was almost a ten percent absolute improvement in progression-free survival in the group that had chemotherapy — 42.4 percent had not had their cancer return or spread outside the liver versus 33.2 percent for those who had surgery alone.

Bernard Nordlinger M.D. presented the results of the international EPOC trial at the ASCO Plenary session on Monday, June 4th.  In discussing the improved progression-free survival with the use of chemotherapy, he concluded:

This treatment should be proposed as a new standard for these patients and should be delivered by a multidisciplinary team.

Nicholas Petrelli, M.D., a surgical oncologist, disagreed that the approach should be the standard first choice for treating resectable liver metastases.  In a discussion following Nordlinger’s presentation, Petrelli pointed out that chemotherapy can harm normal liver tissue and lead to surgical complications.

He said that doing surgery first is still a good option for people whose liver metastases are resectable.

He called for a clinical trial to compare effectiveness of both pre and post surgical chemotherapy to improve survival.

SOURCE: Nordlinger et. al. Abstract #LBA5 ASCO 2007.

NEWS FROM ASCO 2007

In an effort to predict which patients might benefit the most from treatment with cetuximab (Erbitux), researchers studied three biological markers in both primary and metastatic colorectal cancers. 

They measured EGFR (epidermal growth factor receptor) levels using both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) tests.  They also measured cchanges copy numbers of the HER2 gene with FISH.  In addition, they tested for mutations in the KRAS gene.

• While IHC tests of EGFR showed no difference in response rates, FISH EGFR positive patients had a significantly higher response rate to cetuximab — 29.3 percent had tumor shrinkage compared to 6.8% of those with negative EGFR FISH.
• Positive EGFR by FISH testing almost doubled the median time to when the cancer began progressing again — 6.6 months versus 3.7 months.
• Increased HER2 gene copy number was associated with shorter time to progression and survival.
• KRAS mutation carriers had a significantly lower response rate (6.4 percent versus 26.5 percent).  They also had shorter median time to progression  (3.7 months versus 6.3 months) and shorter survival (8.3 versus 10.8 months).

Giovanna Finocchiaro  M.D. presented the results of the study at ASCO:

This study, the largest biomarker analysis in colorectal cancer patients treated with cetuximab, shows a significant benefit in response and TTP for EGFR FISH positive patients. KRAS mutation analysis identifies a group of patients with the lowest chance to benefit from the therapy. Increased HER2 gene copy number predicts early escape from cetuximab therapy.

Combining EFGR status determined by FISH analysis and KRAS mutations may predict those patients most likely to benefit from cetuximab and help others avoid its expense and side effects.

SOURCE:  Finocchiaro et. al. Abstract #4021 ASCO 2007

NEWS FROM ASCO 2007

When cetuximab (Erbitux®) was added to a combination of irinotecan, leucovorin, and fluorouracil (FOLFIRI), both response rates and progression-free survival improved.

The phase III CRYSTAL trial randomized 1200 patients who had not had previous chemotherapy for metastatic colorectal to receive either

• Standard arm: FOLFIRI regimen of intravenous irinotecan and leucovorin followed by a 46 hour continuous infusion of 5FU every two weeks.
• Experimental arm: Weekly infusion of cetuximab added to the FOLFIRI treatment.

Cetuximab improved progression free survival by 15%, with median time to when cancer got worse of 8.0 months for FOLFIRI alone and 8.9 months for the combination treatment of FOLFIRI plus cetuximab.

At one year 23 percent of patients on FOLFIRI had not had any progression compared to 34 percent of those on the experimental cetuximab arm.

More patients had their tumors shrink while on the experimental arm that included cetuximab (46.9 percent versus 38.7 percent).

Three times as many patients on the cetuximab arm were able to have liver metastases successfully removed. (6 percent vs. 2.5%).  Among patients whose only metastases were in their livers, nearly 10 percent who initially could not have a surgery to remove them were able to have complete resection surgery after treatment with the FOLFIRI plus cetuximab.

Grade 3 or 4 serious side effects included low white cell counts, vomiting, and fatigue that were similar in both arms.  There was slightly more severe diarrhea in the cetuximab arm (10.5 percent versus 15 percent.)  Nearly 20 percent of the cetuximab patients experienced a serious skin rash, and 2.3 percent had a reaction during the infusion.

Skin reactions were strongly related to length of progression-free time, with those having the most severe rash also having the longest progression-free survival.

Eric Van Cutsem reported the CRYSTAL results at ASCO, concluding:

Cetuximab in combination with FOLFIRI significantly increases response rate and significantly prolongs PFS in the first-line treatment of pts with mCRC, reducing the relative risk of progression by approximately 15%. Treatment-related side effects of cetuximab in combination with FOLFIRI were as expected, with diarrhea being moderately and skin reactions significantly more frequent as compared to FOLFIRI alone.

WHAT THIS MEANS FOR PATIENTS

Patients newly diagnosed with metastatic colorectal cancer have another option for treatment.  The FOLFIRI plus cetuximab treatment may be especially helpful to those with with liver-only mets that are initially not able to be removed surgically — shrinking them so they can be treated with surgery and potential cure.