stereotactic radiosurgery and herceptin

[rose]

My onc was told today that herceptin is a radiosensitizer and should not be given the week of stereotactic surgery. Has anyone else heard this or been told to hold herceptin for that week? It was news to me!

[pattyz]

News to me, too. But this could be a recent finding...or could be misinformation. Just don't know for sure. I haven't seen any documentation on it.

Some drugs ARE radiosensitizers and are given for that purpose with radio resistant tumors.

It won't hurt to forego the Herceptin for this short a time.

hugs,
pattyz

[jeff]

Hello,

Below find an abstract presented at this past year's breast cancer conference in San Antonio. It's about a small study that shows herceptin to be a radiosensitizer. And suggests that for local control of disease in the breast that's a good thing. I'm not sure why it might be a bad thing elsewhere.

Good luck!
Jeff
P.S. I found this abstract at www.sabcs.org
[1042] Radiosensitization of locally advanced breast cancer with herceptin initial toxicity results of a phase II trial.

Sartor CI, Graham M, Carey L, Dees C, Ollila D, Sherron R, Halle J UNC School of Medicine and Lineberger Comprehensive Cancer Center, Chapel Hill, NC

Purpose/Objective: Patients with locally advanced, chemotherapy refractory breast cancer have poor local control with standard radiotherapy (RT). Preclinical studies demonstate that Herceptin radiosensitizes HER2 over-expressing breast cancer cells. We hypothesized that concurrent pre-operative RT and Herceptin would be well-tolerated, and would result in improved response in patients with residual disease after neoadjuvant chemotherapy.
Methods: Patients with T4, N2, or M1 breast cancer with measurable locoregional residual disease after neoadjuvant chemotherapy were eligible for pre-op RT and prospectively enrolled. To receive Herceptin, patients also must have normal cardiac function and biopsy-confirmation of residual HER2 over-expressing disease after chemotherapy. Treatment consisted of 50Gy to the breast and regional nodes concurrent with weekly, concurrent Herceptin (2mg/kg) followed by mastectomy. Primary endpoints were toxicity (acute skin, cardiac), and efficacy as determined by pathologic response. Acute toxicity and response were evaluated weekly during therapy. Cardiac function and disease status were evaluated every 6 months following completion of radiotherapy. Median follow-up is 23 months.
Results: 16 patients met disease eligibility criteria and were treated with pre-op RT. Seven of the 16 were ineligible to receive concurrent Herceptin due to inadequate cardiac function (6) or lack of confirmation of HER2 over-expressing residual disease (1), and serve as a control group. Herceptin-RT was well tolerated in the 9 patients who received the combined treatment. Two experienced grade 3 acute skin toxicity (both treated with bolus), and 1 prematurely terminated treatment due to grade 2 skin toxicity. No patients developed symptomatic cardiotoxicity, had decline in serial LVEF to below normal limits, or developed late toxicity. Toxicity was similar in the control group; 1 of 7 developed grade 3 acute skin toxicity and post-surgical wound complication. Some efficacy data is available as this early stage of the trial. Although the protocol stipulated mastectomy at the completion of neoadjuvant radiotherapy, only 3 of the 9 patients treated with Herceptin-RT received mastectomy, due to patient or physician preference. There were no pathologic complete responses. Interestingly, of the patients who declined surgery, 3 remained locally controlled for more than 1 year, and none have developed isolated locoregional progression despite the low radiotherapy dose.
Conclusions: In this ongoing Phase II trial, neoadjuvant radiotherapy with Herceptin is well-tolerated. While this trial was not designed to investigate the ability of Herceptin to enhance response to primary radiotherapy, durable local control of gross disease after only 50Gy suggests that Herceptin may be an effective radiosensitizer.
Supported by Genentech, Inc. and CA83753 to CIS

[Paul]

Rose,

I have to agree with Jeff. Although the area of herceptin as a radiosensitizer requires much more study, there are small, mainly in vitro studies, that suggest it is. The cross-link below will take you to one such study conducted by M.D. Anderson.

If most studies, albeit small ones, suggest herceptin is a radiosensitizer, I'm not sure what issue your doctor is raising. As Jeff suggested, the ability of a drug to make cancer more radiosensitive prior to or during radiation treatment is a good thing.

In addition, Herceptin generally does not penetrate the blood-brain barrier (BBB), so I'm not sure why it is an issue in the first place with respect to stereotactic surgery on the brain. Some patients believe that herceptin may penetrate the BBB in some quantity after whole brain radiation as general radiation is know to cause a breach of the BBB. Such belief is purely anecdotal.