Study Supports Activity of Gemcitabine in Treatment of Early-Stage Breast Cancer

October 1, 2007
Oncology, ONCOLOGY Vol 21 No 11, Volume 21, Issue 11

Gemcitabine (Gemzar), which is approved in combination with paclitaxel (Taxol) in the first-line, postsurgical treatment of metastatic breast cancer, was the subject of a study presented at the 43rd annual meeting of the American Society of Clinical Oncology (ASCO), with encouraging results in the presurgical treatment of breast cancer.

Gemcitabine (Gemzar), which is approved in combination with paclitaxel (Taxol) in the first-line, postsurgical treatment of metastatic breast cancer, was the subject of a study presented at the 43rd annual meeting of the American Society of Clinical Oncology (ASCO), with encouraging results in the presurgical treatment of breast cancer.

Promising Regimen

Results of the study showed that adding gemcitabine to the current standard-of-care treatment was a promising regimen for patients with stage II/III breast cancer. The phase II investigation (abstract #595) evaluated the addition of gemcitabine to the current standard-of-care of epirubicin (Ellence) and cyclophosphamide followed by paclitaxel in patients with stage II/III breast cancer. The treatment schedule was a dose-dense sequential neoadjuvant (presurgical) 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). In addition, patients who tested positive for the HER2 gene also were given trastuzumab (Herceptin) and demonstrated additional response.

More About the ASCO Trial

The trial enrolled stage II/III breast cancer patients (with a median age of 45 years), 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 investigation, 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 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 gemcitabine (150/2,500 mg/m2) for six cycles. Treatment was administered on day 1, every 2 weeks, with growth factor support. HER2-positive patients (20 patients, 27.3%), were given trastuzumab (2 mg/kg with a loading dose of 4 mg/kg) concomitantly. Afterward, the patients underwent surgery, radiotherapy, and adjuvant hormonal therapy according to individual institutional practice.

All patients from the study showed a response to the regimen. Of the entire study group, 27 patients (36.9%) achieved a pCR, with 50% representation from the HER2-positive patients who also were given trastuzumab. A total of 47 patients (64.4%) underwent conservative surgery.

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

Aggressive Research Plan

"The data [presented at the ASCO meeting] reflects our ongoing, aggressive research plan involving Gemzar as a key therapeutic foundation for the treatment of breast cancer," said Allen Melemed, MD, medical director, global oncology at Eli Lilly and Company, the manufacturer and marketer of gemcitabine. "We are encouraged with the activity Gemzar has shown in this breast cancer study."

Lilly has also cited five completed or ongoing phase III trials that will further study gemcitabine as a chemotherapeutic foundation for the treatment of early-stage breast cancer. 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 gemcitabine to commonly used treatment regimens.

Two adjuvant (postsurgical) therapy trials, National Surgical Adjuvant Breast and Bowel Project (NSABP) B-38 (4,400 patients) and tAnGo (paclitaxel, Anthracycline, Gemcitabine, and cyclophosphamide, 3,000 patients), will compare the addition of gemcitabine to the paclitaxel arm of each study. A third adjuvant trial, SUCCESS (3,600 patients), is designed to compare the addition of gemcitabine 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 gemcitabine to the paclitaxel or docetaxel arm of the treatment regimen. For additional information on any of these investigations, log on to www.lillytrials.com or www.clinicaltrials.gov.

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