Phase I trial of weekly docetaxel, weekly doxorubicin, daily oral cyclophosphamide, and G-CSF (ConTAC regimen) in advanced malignancies.

PURPOSE: This was a phase I study evaluating the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD) of weekly docetaxel, doxorubicin and daily oral cyclophosphamide with G-CSF support (ConTAC regimen).

PATIENTS AND METHODS: Cohorts of 3-6 patients with advanced breast or other solid malignancies were entered at subsequently higher dose levels until dose-limiting toxicities (DLT) were noted in 2 or more patients per dose level during the first 6 weeks of therapy. This study escalated dosages of docetaxel and doxorubicin simultaneously, while the dose of oral cyclophosphamide was fixed at 60 mg/m(2) daily.

RESULTS: Sixteen patients were enrolled. Grade 3-4 adverse events during the first 6 weeks of treatment were neutropenia (n = 1 at dose level #1 and n = 3 at dose level #4), anemia (n = 2 at dose levels 1 and 4), and nausea/vomiting (n = 1 at dose level #4). After 6 weeks of therapy, grade 3-4 toxicities included anemia (n = 3), neutropenia (n = 7), Hand-Foot syndrome (n = 2) and grade 3 cystitis and pneumonia (n = 1 at dose level #4). Five patients with advanced breast cancer and 1 patient with metastatic lung cancer responded to the chemotherapy.

CONCLUSIONS: Grade 4 neutropenia was the DLT. The MTD, was established at dose level #3 (doxorubicin at 25 mg/m(2) and docetaxel at 25 mg/m(2) weekly with oral cyclophosphamide dose of 60 mg/m(2) daily). Myelosuppression at that dose level was moderate with G-CSF given concurrently.