Severe myelosuppression from piperazinedione, (NSC No. 135758), cyclophosphamide plus dimethyl-triazeno-imidazole carboxamide (DTIC).
In order to determine whether piperazinedione used in low doses in combination with cyclophosphamide plus dimethyl-triazeno-imidazole carboxamide (DTIC) produced variable or severe myelosuppression, a Phase I Study was performed in 10 patients who received 16 courses of the three-drug combination. Although mild myelosuppression was consistently observed at doses of 4 mg piperazinedione, 400 mg cyclophosphamide, plus 400 mg DTIC, variable, severe, and prolonged myelosuppression was seen in three of six patients who received a dose of each of the drugs only 25% higher. The only other abnormality observed was nausea and vomiting. This study indicates that low doses of piperazinedione can produce variable and severe myelosuppression when used in combination with other myelosuppressive agents, and that only small increments in dosage may produce marked increases in the degree of myelosuppression. Future combination chemotherapy regimens employing piperazinedione should undergo cautious Phase I toxicity testing to avoid severe depression of blood counts.
D001853:Bone Marrow / Q000187:drug effects*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D003606:Dacarbazine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects*; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D014226:Triazenes / Q000627:therapeutic use*
D010879:Piperazines; D010880:Piperidines; D014226:Triazenes; C003905:3,6-bis(5-chloro-2-piperidyl)-2,5-piperazinedione; D003606:Dacarbazine; D003520:Cyclophosphamide