ALTTO study and cooperative group trial modified (tykerb dose reduced) due 2 diarrhea

[Lani]

High-Dose Lapatinib in Breast CA Protocol Causes Diarrhea

Jun 10 - In trial of lapatinib and dose-dense chemotherapy for HER2-positive metastatic breast cancer, nearly half the women withdrew because of toxicities -- mainly grade 3 diarrhea associated with the lapatinib, according to a May 17th online report in the Journal of Clinical Oncology.

"We found that lapatinib at 1000 mg daily could not be administered with weekly paclitaxel and trastuzumab as 43% of the patients required a dose reduction of lapatinib."

As a result, researchers have modified the large ALTTO trial and a cooperative group study, "in which the dose of lapatinib is now reduced to 750 mg daily when given with weekly paclitaxel and trastuzumab," she said.

Previously, Dr. Dang and her colleagues at Memorial Sloan-Kettering Cancer Center in New York had established the utility of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab.

"To build on this finding, we conducted this study to test the feasibility of adding lapatinib to weekly paclitaxel and trastuzumab" after the doxorubicin and cyclophosphamide, she said.

For the phase II trial, the researchers enrolled 95 patients with stages I to III disease. The patients received doxorubicin and cyclophosphamide (60mg/m2 and 600 mg/m2) for 4 cycles every 2 weeks with pegfilgrastim (6 mg on day 2) followed by paclitaxel (80 mg/m2) for 12 doses IV weekly continuously.

They also received trastuzumab, in a 4 mg/kg loading dose followed by 2 mg/kg weekly during chemotherapy (and 6mg/kg every third week afterward) along with 1,000 mg of lapatinib orally daily.

The aim was to treat patients for one year. At a median follow-up of 22 months, 92 were evaluable. Forty-one (45%) had withdrawn because of paclitaxel/trastuzumab/lapatinib-specific toxicities.

"As we strive to improve outcomes through the addition of new target agents, it remains critically important to establish feasibility and provide guidance for the management of toxicities through phase II studies" like this one, the authors conclude.

The study was supported by GlaxoSmithKline, which markets lapatinib as Tyverb and Tykerb.

http://jco.ascopubs.org/cgi/content/...2009.26.5900v1

J Clin Oncol 2010.

[Nancy L]

After six days on 1000mg of Tykerb, I had massive hives all over my body. Dr. Slamon reduced my dosage to 750mg a day plus Herceptin every three weeks. I have been on that reduced dosage for 15 months and am currently NED. I believe in taking the least amount of medication to get the job done. All of our body types are different and prescribing the same for everyone is easy for the oncs but doesn't make sense to me. I must say I still have episodes of chronic diarrhea at 750mg per day but control it with Lomotil and diet.