Moderate-dose vincristine infusion in refractory breast cancer.

Continuous infusion of vincristine at the maximally tolerated infusion dosage of 0.5 mg/m2/day for 5 days has been investigated in 15 patients with refractory breast cancer. Infusion courses were repeated every 3 weeks in the absence of disease progression or prohibitive toxicity. Progressive disease was observed in 14 patients. A partial response lasting 2 months occurred in a patient with pulmonary and skin metastases who had previously received vincristine by bolus injection. Toxicity consisted primarily of mild neurotoxicity of similar degree to that expected with bolus injection. Thrombocytopenia occurred, but was uncommon. The cumulative response rate at this dosage level (2/16, 13%) in our phase I-II trials indicates very limited clinical activity of vincristine infusion in advanced, refractory metastatic breast cancer.

Clinical trial of folinic acid to reduce vincristine neurotoxicity.

In a murine model system, folinic acid demonstrated host-protective properties during administration of repetitive and lethal doses of vincristine (VCR). Subsequently, folinic acid was evaluated in patients receiving VCR during an adjuvant chemotherapy program for stage II carcinoma of the breast. The toxicities, cumulative VCR dosage, and percentage of ideal dosage observed in 18 patients receiving folinic acid have been compared with those observed in 70 patients who previously received VCR without folinic acid in the same chemotherapy program. All patients ideally were intended to receive VCR 1.0 mg/m2 weekly for 6 weeks, with dose modification for neurotoxicity. Treatment patients received folinic acid 800 mg PO daily in three divided doses during the 6-week course. The degree of neurotoxic manifestations of VCR was similar in the treatment and comparison patients. Absent to mild neurotoxicity was observed in approximately 70% of patients in both groups; moderate or greater neurotoxicity occurred in about 30% of patients in both groups. Full dosage (6.0 mg/m2) was attained in 7 (39%) treatment patients and 17 (24%) comparison patients (P = 0.21). The mean percentage of the ideal dosage of VCR was 73.7 +/- 28.7 in patients receiving folinic acid and 76.1 +/- 20.5 in those given only VCR (P = 0.69). Hematologic toxicities were similar in both groups, but nausea occurred more frequently in the folinic acid group. Folinic acid in this dose and schedule afforded no protection from the neurotoxic side effects of VCR.

Clinical trial of pyridoxine to reduce vincristine neurotoxicity.

In a murine model system, pyridoxine has demonstrated protective properties during administration of lethal doses of vincristine (VCR). Subsequently, pyridoxine has been evaluated in patients receiving VCR during an adjuvant chemotherapy program for stage II carcinoma of the breast. The toxicities, cumulative VCR dosage, and percentage of ideal dosage observed in 24 patients receiving pyridoxine have been compared to those observed in 88 patients who previously received VCR without pyridoxine in the same chemotherapy program. All patients ideally were to receive VCR 1.0 mg/m2 weekly for 6-weeks with dose modification for neurotoxicity. Treatment patients received pyridoxine 1.5 grams p.o. daily in three divided doses during the 6-week course. The degree of neurotoxic manifestations of VCR was similar in the treatment and comparison patients. Absent to mild neurotoxicity was observed in approximately 70% of patients in both groups; moderate or greater neurotoxicity occurred in about 30% of patients in both groups. Full dosage (6.0 mg/m2) was attained in 8 (33%) treatment patients and 18 (24%) comparison patients (p = 0.28). The mean percentage of ideal dosage of VCR was 84.6 +/- 10.8 in patients receiving pyridoxine and 81.9 +/- 21.6 in those given only VCR (p = 0.59). Gastrointestinal and hematologic toxicities were similar in both groups. Pyridoxine in this dose and schedule afforded no protection from the neurotoxic side effects of VCR.