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Erbitux Plus Chemo Can Make Liver Mets Surgery Possible

Chemotherapy and Erbitux® (cetuximab) reduced liver tumors from colorectal cancer enough for patients to have them removed surgically.

Although their cancer was initially too extensive to be surgically removed (resected) chemotherapy combined with Erbitux allowed about a third of patients to have surgery that completely removed all visible signs of liver tumors.  Tumor shrinkage occured in about two out of three patients, despite which chemotherapy was used.

During a phase II clinical trial in Germany and Austria, 111 patients with colorectal cancer that had spread to their liver were treated with Erbitux and either FOLFOX6 (oxaliplatin, fluorouracil, and leucovorin) or FOLFIRI (irinotecan, fluorouracil, and leucovorin).  All were considered to have liver tumors that could not be removed surgically.

Every eight weeks, CT scans or MRIs were used to measure any tumor shrinkage (response). After 16 weeks and then every 8 weeks for two years, a local, multidisciplinary team decided whether the situation had changed and patients were able to have surgery.

The study found:

  • 38 of 53  patients (68 percent) on FOLFOX6 had a partial or complete response to treatment with measurable tumor shrinkage compared to 30 of 53 (57 percent) of those on FOLFIRI.  This difference between chemotherapies was not significant.
  • 20 of 53 patients (38 percent) on FOLFOX were able to have surgery that removed all signs of cancer in the liver, including tumor margins (R0 resection) while 16 of 53 (30 percent) of FOLFIRI patients had an R0 resection.  Again, this was not a significant difference.

The study included patients with both KRAS and BRAF mutations.  Normal or wild-type KRAS made a difference in response to treatment with 70 percent of KRAS wild-type tumors shrinking compared to 41 percent of tumors with KRAS mutations.

Serious side effects included skin rash in 34 percent of patients and lowered white cell counts (neutropenia) in 23 percent.

Dr. Gunner Folbrecht and the CELIM team concluded,

Chemotherapy with cetuximab yields high response rates compared with historical controls, and leads to significantly increased resectability.

After the trial was over, a team of radiologists reviewed patient scans at the beginning and end of treatment to access how many could have had surgery initially and how many after chemotherapy (resectability rate). The radiologists didn’t know which patients had been able to have surgery or what chemotherapy they received.  The team found that the percentage whose tumors could have been operated on almost doubled during treatment from 32 percent initially to 60 percent after chemotherapy with Erbitux.

In a comment in HemOnc Today, Alan Vernook, MD, points out that although all patients had to have unresectable tumors to be included in the trial, the blinded retrospective review found that almost a third could have had surgery initially.  He urges multidisciplinary team involvement in treatment of patients with liver mets.

One interesting finding is that these patients were deemed unresectable at the outset as part of eligibility criteria. Yet, in a blinded independent retrospective review, about 30% of the patients were felt to be resectable. So, on one hand, the treatment effect of this study brings us the hope that in KRAS wild-type patients, cetuximab plus chemotherapy may make more patients resectable. But, it also raises the question that deeming who is resectable at the outset is in the eye of the beholder. So, this study emphasizes the need for more and more multidisciplinary therapy and the idea that one surgeon’s unresectable is another surgeon’s resectable.

SOURCE:  Folprecht et al, The Lancet, early online November 25, 2009.

Disclosure: C3 has accepted funding for projects and educational programs from ImClone Systems and Eli Lilly in the form of unrestricted educational grants. C3 has ultimate authority over website content.

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