Phase II trial of gemcitabine as prolonged infusion in metastatic breast cancer

Gemcitabine is an active agent in the treatment of metastatic breast cancer . The phosphorylation of gemcitabine into the active gemcitabine triphospha te (dFdCTP) is catalyzed by deoxycytidine kinase. This enzyme is saturated at plasma concentrations achieved after an infusion over 30 min. Therefore accumulation of higher intracellular dFdCTP concentrations, which may resul t in an enhanced antineoplastic activity, cannot be achieved by higher dosa ge, but only by prolonged infusion time. In a previous phase I trial the ma ximum tolerated dose of gemcitabine given as a 6 h i.v. infusion was 250 mg /m(2). The objective of this phase II trial was to determine the efficacy a nd safety of gemcitabine as prolonged infusion in patients with metastatic breast cancer. Twenty patients [median age 50.4 years, range 35-63 years; performance stat us EORTC 0 (17 patients), 1 (two patients), 2 tone patient)] with metastati c breast cancer were treated with 250 mg/m(2) gemcitabine as infusion over 6 h on days 1, 8 and 15 q3 weeks for up to six courses (median 3.9 courses) . Treatment was first line for four patients, second line for five patients and third line or higher for 11 patients. Metastatic sites were liver in 1 4 patients, bone in 12 patients, lung in eight patients and lymph nodes in nine patients. Nine patients presented two metastatic sites, three patients three and five patients four. All patients were evaluable for response and toxicity. One patient (5%) achieved a complete remission (CR) and four patients (20%) a partial remission (PR) tone patient with CR of visceral metastases but s table bone metastases), for an overall response rate of 25% (five of 20). I n addition, six patients (30%) had stable disease and nine (45%) failed to respond to the treatment. Time to progression ranged from 2 to 23 months wi th a median of 6.3 months. Hematologic toxicity was mild with leukopenia gr ade 3 in only three patients (15%) and no grade 3 thrombocytopenia. Moderate elevations of liver enzymes (three patients grade 3), nausea and v omiting (two patients grade 2), and mild alopecia were observed, but only o ne patient had to be withdrawn due to toxicity. In conclusion gemcitabine a s prolonged infusion is an effective treatment in metastatic breast cancer. Toxicity, especially myelosuppression, is surprisingly mild. Therefore, ge mcitabine seems to be ideal for combination therapies. [(C) 1999 Lippincott Williams & Wilkins.]