Combination docetaxel/cyclophosphamide in patients with advanced solid tumors.
Preclinical studies show that docetaxel (Taxotere) and cyclophosphamide (Cytoxan, Neosar) are synergistic against MA 13/C mammary adenocarcinoma. Both agents are highly active as monotherapy in a number of tumors, including metastatic breast cancer. Therefore, we performed a phase I dose-finding study to determine the maximum tolerated dose of this combination regimen in patients with advanced solid tumors. A total of 45 patients were enrolled and received cyclophosphamide followed by docetaxel, both administered as 1-hour intravenous infusions once every 3 weeks. The dose levels of cyclophosphamide/docetaxel were 600/60 mg/m2 (group 0), 600/75 mg/m2 (group I), 700/75 mg/m2 (group 2), 800/75 mg/m2 (group 3), 800/85 mg/m2 (group 4), 800/75 mg/m2 (group 5), and 800/85 mg/m2 (group 6). Patients with dose-limiting neutropenia in groups 5 and 6 received 300 micrograms of granulocyte colony-stimulating factor (G-CSF) (filgrastim [Neupogen]) support on days 2 through 9 during subsequent cycles of chemotherapy. All patients received premedication with 8 mg of dexamethasone twice daily for 5 days, beginning 1 day prior to chemotherapy. The dose-limiting toxicity was neutropenia fever. The recommended dose for phase II studies of cyclophosphamide/docetaxel is 700/75 mg/m2 in previously treated patients and 800/75 mg/m2 in previously untreated patients. G-CSF support did not allow for further dose escalation. Preliminary results from this phase I trial indicate that the combination of docetaxel and cyclophosphamide produced an objective response rate of 69% in 32 patients with metastatic breast cancer (including 3 patients who achieved complete responses).
Valero
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University of Texas M. D. Anderson Cancer Center, Houston, USA.
D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy; D017322:Clinical Trials, Phase II as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000627:therapeutic use; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000139:chemically induced; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011292:Premedication; D012074:Remission Induction; D012509:Sarcoma / Q000188:drug therapy; D043823:Taxoids
D000932:Antiemetics; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D003907:Dexamethasone; D003520:Cyclophosphamide; D017239:Paclitaxel