Shorter interval between cycles of cyclophosphamide, doxorubicin, cisplatin using recombinant human granulocyte colony-stimulating factor for urothelial cancer--phase I/II study.

BACKGROUND

Despite improvement in the response rate and protraction of the progression-free period of urothelial cancer produced by chemotherapy, severe bone marrow suppression often results in delays in the initiation of treatment cycles and/or decreases in drug dosages. Reduction of leukopenia during chemotherapy has been demonstrated by the combined administration of granulocyte colony-stimulating factor (G-CSF) in various malignancies.

METHODS

A phase I/II study was conducted to assess whether the interval between cycles of CISCA (cyclophosphamide, doxorubicin, cisplatin) chemotherapy could be shortened under support of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for urothelial cancer. Three or more patients with transitional cell carcinoma of the urinary tract were allocated to each of four different treatment intervals (step 1: 28 days, step 2: 21 days, step 3: 17 days, and step 4: 14 days) by reducing the interval in a step-wise manner. Two mg/kg/day of a rhG-CSF, lenograstim, was injected subcutaneously on days 3 to 16 (until day 14 for the 14-day interval group).

RESULTS

Sixteen patients were enrolled, four patients were treated with the step 1 protocol, five with step 2, four with step 3, and three with step 4. Leukopenia/neutropenia was the most severe toxic reaction, but none of the patients at any step manifested neutropenia of WHO grade 4 for more than four days. There were no significant differences in the hematological and nonhematological toxicities among the 4 steps. Seven of eight patients with measurable diseases were treated with CISCA on shortened schedules (steps 2-4), and one complete remission (CR) and four partial responses (PR) were demonstrated.

CONCLUSIONS

CISCA chemotherapy supported by rhG-CSF was safely shortened to a 14-day interval in the pilot study. The potential role of rhG-CSF in shortening the interval of CISCA, as well as the benefit of the intensified schedule, remains to be clarified.