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Historically, vinblastine given by intravenous bolus injection has not been an effective treatment for non-Hodgkin's lymphomas; vincristine has displayed greater activity. Also, vinblastine has generally been considered to be cross-resistant with vincristine in such patients. In an attempt to overcome these obstacles, a protracted infusion of vinblastine was administered (0.5-1.5 mg/m2 per day for 5 days) and repeated every 3 weeks. Partial responses were observed in 4 of 29 (14%) patients with a variety of non-Hodgkin's lymphoma lasting 2.4, 2.4, 5.5, and 9.0 months. Just prior to treatment the responding patients had received and eventually become refractory to vincristine. These data show a lack of total cross-resistance between vinblastine and vincristine which might have important therapeutic implications in this disease.

Actinomycin D is generally administered by serial low-dose injection over 5–10 days. Recent recognition of prolonged serum and tissue half-lives suggests that high-dose intermittent injection should be equally effective and less toxic. An intermittent single dose schedule was selected for this phase II trial of actinomycin D in 23 patients with advanced breast cancer refractory to standard combination chemotherapy. The drug was given in doses of 0.75–1.5 mg/m2 at 2-week intervals or on days 1 and 8 of 28-day treatment cycles. One patient obtained a partial response with a duration of 5.7 months. Four patients experienced stabilization of advanced disease, with a mean duration of response of 6.4 months. Gastrointestinal toxicity occurred in 47% of patients and mild to moderate myelosuppression in 39%. We conclude that actinomycin D in this dosage and schedule has limited activity in advanced breast cancer. Higher doses might result in increased response rates but would be associated with greater toxicity.