Evaluation of a Gemcitabine‐Doxorubicin‐Paclitaxel Combination Schedule through Flow Cytometry Assessment of Apoptosis Extent Induced in Human Breast Cancer Cell Lines

Combination chemotherapy with gemcitabine (Gem), doxorubicin (Dox), and paclitaxel (Pac) (GAT) has been considered attractive as first‐line treatment in metastatic breast cancer. We compared the potential of various schedules of GAT to induce apoptosis on MDA‐MB–231, MCF7, and T47D human breast cancer cell lines. The extent of apoptotic induction was analyzed by flow cytometry with 7–aminoactinomycin D (7AAD) staining. Differences between various schedules in terms of apoptotic induction were statistically significant (P<0.05). The most effective apoptotic induction regimen was achieved by the sequence: Dox for 16 h followed by Pac+Gem. Schedules employing a 16–h interval between drug administrations induced higher levels of apoptosis in human breast cancer cell lines compared with schedules using a 4–h interval. The therapeutic efficacy of the experimental results shown in this paper has been clinically corroborated in a phase II trial in metastatic breast cancer patients.