You are here: Home: CCU 5 | 2007: Joel E Tepper, MD

Tracks 1-15

Track 1 Current clinical trial objectives in rectal cancer Track 2 Clinical trials evaluating oxaliplatin as part of neoadjuvant therapy of rectal cancer Track 3 Use of capecitabine as part of treatment of rectal cancer Track 4 Combining EGFR inhibition with radiation therapy in rectal cancer Track 5 Vascular normalization as a rationale for combining bevacizumab with radiation therapy Track 6 Tumor and nodal staging errors with the use of endoscopic ultrasound Track 7 Role of MRI in rectal cancer Track 8 Treatment algorithm for local and systemic therapy of rectal cancer Track 9 Use of postoperative adjuvant chemotherapy for rectal cancer Track 10 Adequacy of lymph node sampling in rectal cancer Track 11 Treatment for patients presenting with synchronous primary rectal tumors and metastatic disease Track 12 Abdominoperineal (AP) resection in the community versus specialty centers Track 13 Local excision for rectal cancer Track 14 New directions in the treatment of anal cancer Track 15 Modification of radiation therapy techniques in the treatment of anal cancer

Select Excerpts from the Interview

Tracks 1-2

DR TEPPER: The major emphases in clinical trial development in rectal cancer are in two separate areas. One is trying to enhance local control to the point of being able to treat rectal cancer without a surgical resection. Virtually all those trials have included radiation therapy and all include a fluoropyrimidine.

People are also interested in using other agents to enhance response to radiation therapy. The new cytotoxics have been studied to a great extent. Irinotecan has been of some interest but is problematic due to the possibility of diarrhea associated with irinotecan being additive to the diarrhea already associated with radiation therapy and the fluoropyrimidine.

Much more interest has been shown in oxaliplatin, which has been evaluated in Phase I and II studies. We performed a Phase I study and the initial parts of a Phase II study, which then went into CALGB as a Phase II study (Ryan 2006).

The study’s aim was to deliver the oxaliplatin in such a way as to optimize radiation sensitization. We used a once-weekly schedule throughout the course of radiation therapy, which is somewhat different from the schedule typically used with oxaliplatin alone as a cytotoxic. The Phase I study suggested that a dose of 60 mg/m² per week would be most appropriate.

Track 3

DR TEPPER: After treating a number of patients, I don’t believe the side effects to be much different. Some questions related to timing remain regarding the combination of capecitabine with radiation therapy. Based on some of the available pharmacokinetic data, we try to deliver the capecitabine approximately an hour and a half before the radiation therapy. I don’t know if that’s better, but it matches up with being at or slightly past the peak concentration of the agent.

DR LOVE: Any reason to believe that capecitabine might be more efficacious than 5-FU when combined with radiation therapy? There has been discussion about whether radiation therapy increases thymidine phosphorylase (TP). Could that in some way synergize with capecitabine better than 5-FU?

DR TEPPER: Yes, the issue of the synergism has been raised, but I’m aware of no clinical data to indicate that it is affecting the overall outcome. The response data appear similar between the agents based on early results, but it’s possible that the NSABP-R-04 study will demonstrate the superiority of capecitabine.

Track 5

DR TEPPER: Bevacizumab is an interesting drug to consider combining with radiation therapy. You would expect that the last thing you would want to do would be to use an anti-angiogenic agent with radiation therapy because shutting down the blood supply could lead to worse results by producing more hypoxic cells and a decreased response to radiation therapy.

That does not appear to be the case because the preclinical data suggest that drugs such as bevacizumab have a beneficial effect when combined with radiation therapy. Work from Rakesh Jain has suggested that what is occurring in these tumors treated with bevacizumab is vascular normalization rather than overall vascular shutdown ( Jain 2001; [2.1]).

By changing intratumoral pressure, we might actually allow better blood flow, better delivery of chemotherapy and better oxygenation effects for radiation therapy.

Few small studies have used bevacizumab with radiation therapy. Thus far, the toxicity appears to be acceptable, but I believe it’s too early to say how encouraged one should be with the results.

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