Study Supports Activity of GEMZAR in the Treatment of Early-Stage Breast Cancer

 Behind the Cancer Headlines®

June 1, 2007 


GEMZAR® (gemcitabine HCl for injection), approved in combination with paclitaxel (Taxol®) in the first-line, post-surgical treatment of metastatic breast cancer, was the subject of a study with encouraging results in the pre-surgical treatment of breast cancer. The study was presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO).  

Results showed that adding GEMZAR to the current standard-of-care treatment was a promising regimen for patients with stage II-III breast cancer. Eli Lilly and Company, the manufacturer and marketer of GEMZAR, also cited five completed or ongoing Phase III trials which will further study GEMZAR as a chemotherapeutic foundation for the treatment of early-stage breast cancer.  

This Phase II study evaluated the addition of GEMZAR to the current standard-of-care of epirubicin and cyclophosphamide followed by paclitaxel in patients with stage II-III breast cancer. The treatment schedule was a dose-dense sequential neoadjuvant (pre-surgical) chemotherapy combination, meaning that the combination was administered at shorter intervals between treatments. Results showed a promising regimen in terms of pathologic complete response (pCR-the absence of invasive tumor in the breast). In addition, patients who tested positive for the HER-2 gene also were given trastuzumab (Herceptin®) and demonstrated additional response.  

“The data released today reflects our ongoing, aggressive research plan involving GEMZAR as a key therapeutic foundation for the treatment of breast cancer,” said Allen Melemed, M.D., medical director, global oncology at Lilly. “We are encouraged with the activity GEMZAR has shown in this breast cancer study.”  

Enrollment has been completed in one trial, and is ongoing in an additional four, Phase III early-stage breast cancer studies evaluating the addition of GEMZAR to commonly-used treatment regimens. Two adjuvant (post-surgical) therapy trials, NSABP B-38 (4,400 patients) and TANGO (3,000 patients), will compare the addition of GEMZAR to the paclitaxel arm of each study. A third adjuvant trial, SUCCESS (3,600 patients), will compare the addition of GEMZAR to a docetaxel-based regimen. Two additional trials, which are neoadjuvant specific, NSABP B-40 (1,200 patients) and Neo-TANGO (800 patients), will evaluate the addition of GEMZAR to the paclitaxel or docetaxel arm of the treatment regimen. 

The trial enrolled stage II-III breast cancer patients (with a median age of 45), including inflammatory tumors, a type of breast cancer that causes the breast to swell, redden and feel warm. Of the 73 patients enrolled in the study, 42 (57.5%) were classified as T2; 12 (16.5%) as T3, and; 19 (26%) as T4, which included 13 patients with inflammatory tumors. A T-classification represents the stage of the tumor with T4 being the most advanced. A biopsy was performed before treatment for the biomarker component of the study.  

Patients received a first sequence of epirubicin and cyclophosphamide (90/600 mg/m2) for three cycles followed by a second sequence of paclitaxel and GEMZAR (150/2500 mg/m2) for six cycles. Treatment was administered on day one, every two weeks, with growth factor support. HER-2 positive patients (20 patients, 27.3%), were given trastuzumab (2 mg/kg with a loading dose 4 mg/kg) concomitantly. Afterward, the patients underwent surgery, radiotherapy and adjuvant hormonal therapy according to institutional practice.  

All patients from the study showed response to the regimen. Of the entire study group, 27 (36.9%) patients achieved a pCR (absence of invasive tumor in the breast), with 50% representation from the HER-2 positive patients who also were given trastuzumab. Forty-seven patients (64.4%) underwent conservative surgery.  

The grade 3/4 hematological toxicities were: leukopenia in six patients (9%); neutropenia (a decrease in white blood cells) in eight patients (12%), and; anemia (a decrease in red blood cells) in one (2%). Nausea (13%) and vomiting (15%) were the most frequent grade 3/4 non-hematological toxicities. Asymptomatic decrease in cardiac ejection fraction was observed in one patient treated with trastuzumab with subsequent normalization. 



Annual Meeting of the American Society of Clinical Oncology, June 2, 2007, Chicago, IL