Home: Web Guide 1: Edward Chu, MD

Edward Chu, MD

Director, Comprehensive Cancer Center VA Connecticut Healthcare System

comments on case presentation

This patient had two main options: standard therapy with capecitabine or enrollment in an experimental protocol. Capecitabine is now approved as front-line therapy, and in patients with prior adjuvant therapy, capecitabine results in about a 20% to 25% response rate. In contrast, if you treat these same patients with 5-FU/leucovorin, the response rate is less than 10%. So for this man, capecitabine was the best option.

dose and scheduling of capecitabine

Since this man was in fairly good shape, we decided to be a bit more aggressive and wanted to push the dose. So, we went with the standard dose of capecitabine — 1,250 mg/m2 orally twice daily with two weeks on and one week off. Fortunately, he tolerated the standard dose extremely well.

response to treatment

This man’s overall performance status has improved. He is eating, not as fatigued and he does not have any right upper quadrant abdominal pain. On palpation, his liver has decreased in size. On CT scanning, both his liver and lung metastases have decreased in size after two cycles of capecitabine. In the past year, my group has switched over to using capecitabine instead of intravenous 5-FU/leucovorin. I have been impressed with how well capecitabine is tolerated as well as its efficacy. We have even seen dramatic responses in some patients receiving capecitabine as third- or fourth-line therapy.

phase i/ii trials of capecitabine in combination with oxaliplatin or cpt-11

At the European Cancer Conference (ECCO), Chris Twelves presented an update on an international phase II trial evaluating capecitabine in combination with oxaliplatin. This study demonstrated quite high response rates with an overall response rate of 55%. These responses were seen across the board amongst a number of different patient subgroups. Capecitabine in combination with oxaliplatin was extremely well-tolerated.

The main toxicities were gastrointestinal in nature, such as nausea, vomiting and diarrhea. Not surprisingly, there was sensory toxicity related to the oxaliplatin. Grade III-IV hand-foot syndrome occurred in less than 5% of the patients. Overall, the safety profile for the capecitabine/oxaliplatin combination was extremely manageable, and the response rates were comparable to those reported for infusional 5-FU/leucovorin/oxaliplatin.

The ECCO meeting also included reports on several different schedules of capecitabine in combination with CPT-11. The bottom line is, on all of these different schedules of administration, response rates were very promising — on the order of 45 to 55 percent. The main dose-limiting toxicities were GI, in the form of diarrhea, and myelosuppression. But for the most part, these have been very well-tolerated. To put this into perspective, the response rates that were seen with capecitabine and CPT-11 are on the same order of responses that were reported initially with the Douillard regimen — CPT-11/infusional 5-FU — and by the Saltz group, using the Saltz regimen.

The hope is that these will quickly go on to phase III studies to show that response rates and efficacy are similar to the Saltz regimen, with a reduced incidence of toxicity. And, certainly, compared to the Douillard European regimen with infusional 5-FU, it may be much easier on the patient. The patients I currently treat in our clinic would prefer to get an oral pill instead of coming to the clinic every day for five days on a weekly basis.

We cannot yet incorporate these newer capecitabine combinations into clinical practice — certainly not capecitabine/oxaliplatin, because oxaliplatin is not yet FDA-approved. Even though CPT-11 is FDA-approved, we need to be cautious and do further studies to ascertain the correct dosing and scheduling.

trials with the chinese herb phy-906

Recently, we have opened to accrual a very interesting study evaluating the Saltz regimen — at full dose — with or without a Chinese herb (PHY 906). The objective of the study is to determine whether or not the Chinese herb is able to protect against some of the toxicities associated with the Saltz regimen. In preclinical in vivo studies conducted in our Yale drug development laboratory, this Chinese herb has allowed the administration of otherwise lethal doses of 5-FU/CPT-11 to mice.

The global toxicity is clearly protected and, if anything, the antitumor activity of 5-FU/leucovorin/CPT-11 may be a little better. The herb is not a pure preparation. It actually has four main ingredients. Within the next 4-6 months, we should have some preliminary idea about the efficacy of this herb.