Rationale and clinical trial design for evaluating gemcitabine as neoadjuvant and adjuvant therapy for breast cancer

Over the past 30 years, much progress has been made in adjuvant chemotherapy for patients with early-stage breast cancer. The introduction of anthracyclines and, recently, taxanes has significantly improved the efficacy of adjuvant chemotherapy and has provided useful insight regarding future development of even more efficacious regimens. However, despite significant progress, there remains considerable room for improvement. Although the manipulation of chemotherapy doses has not been found to be a successful strategy, manipulation of the interval of chemotherapy administration recently showed promise. It appears, nonetheless, that introducing new chemotherapy agents into the adjuvant setting is a more promising strategy than attempting to optimize the dose and schedule of existing agents. Gemcitabine has demonstrated significant antitumor activity in patients with advanced breast cancer when used either as a single agent or in combination with other active drugs (as a double or a triplet). Most of the available information to date has been obtained by combining gemcitabine with anthracyclines and/or taxanes. This approach has shown considerable antitumor activity and a reasonable toxicity profile, making it an important strategy for developing new adjuvant and neoadjuvant chemotherapy regimens. Several currently ongoing and planned adjuvant trials are incorporating gemcitabine (either sequentially or in combination) into anthracycline/taxane regimens. These trials will be important in establishing a role for this agent in the adjuvant setting and will hopefully lead to the development of more effective adjuvant chemotherapy regimens in the future.