Combination docetaxel/cyclophosphamide in patients with advanced solid tumors

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Docetaxel (Taxotere) and cyclophosphamide (Cytoxan, Neosar) exhibit synergistic activity against mammary adenocarcinoma in preclinical models.
• Both docetaxel and cyclophosphamide demonstrate significant efficacy as monotherapy in various tumors, including metastatic breast cancer.

Purpose of the Study:

• To conduct a phase I dose-finding study to establish the maximum tolerated dose (MTD) of the combination regimen of docetaxel and cyclophosphamide.
• To evaluate the safety and tolerability of escalating doses of this combination in patients with advanced solid tumors.

Main Methods:

• A total of 45 patients with advanced solid tumors were enrolled in the phase I study.
• Patients received cyclophosphamide followed by docetaxel intravenously every 3 weeks, with dose escalation across several cohorts.
• Dose-limiting toxicity was defined as neutropenic fever, and granulocyte colony-stimulating factor (G-CSF) support was utilized in later cohorts.

Main Results:

• The recommended dose for phase II studies was determined to be 700/75 mg/m² for previously treated patients and 800/75 mg/m² for previously untreated patients.
• Neutropenic fever was identified as the dose-limiting toxicity.
• In a subset of 32 patients with metastatic breast cancer, the combination regimen achieved an objective response rate of 69%, including 3 complete responses.

Conclusions:

• The combination of docetaxel and cyclophosphamide is a promising regimen for advanced solid tumors, particularly metastatic breast cancer.
• The recommended doses for phase II trials provide a basis for further clinical investigation of this synergistic combination.