Phase I trial of escalating dose doxorubicin administered concurrently with alpha 2-interferon.

The clinical use of alpha 2-interferon and doxorubicin is based on in vitro and preclinical in vivo observations of synergistic antitumor efficacy. To test this combination a Phase I clinical and pharmacokinetic study of the concurrent use of alpha 2-interferon and doxorubicin was initiated in patients with malignant solid tumors. Each 5-wk treatment cycle consisted of 3 wk of drug administration and 2 wk of rest. The alpha 2-interferon was administered s.c. at a constant dose of 10 million IU/m2 on Mondays, Wednesdays, and Fridays in all patients while the doxorubicin was administered weekly beginning with a dose of 5 mg/m2 and escalated to the maximum tolerated dose of 25 mg/m2. At least three evaluable patients were entered at each dose level, and no dose escalations were allowed within patients. The dose-limiting toxicities were granulocytopenia and thrombocytopenia. Hepatic enzyme elevations and systemic symptoms due to interferon occurred at all dose levels. None was severe or dose limiting, and all were reversible. These toxicity data suggest that the hepatotoxic effects of interferon do not enhance doxorubicin toxicity when given by this dose and schedule. Doxorubicin plasma levels were measured at each dose level. The recommended dose of doxorubicin is 25 mg/m2 per wk when administered with 10 million IU/m2 of interferon in this schedule. This schedule allows for the administration of a greater total dose of doxorubicin than has been achieved when given every 3 wk with the same dose and schedule of alpha 2-interferon in a parallel study.

Single-dose dacarbazine and dactinomycin in advanced malignant melanoma.

Twenty-one patients with advanced malignant melanoma were treated with dacarbazine at a dose of 800 mg/m2 as a single infusion and dactinomycin at a dose of 1.2 mg/m2 every 3 weeks. Hematologic toxicity was mild and gastrointestinal toxicity was tolerable. The response rate for evaluable patients was 22%, which included both men and women with visceral disease. Three of the four responses were complete. Durations of response were 4, 6, 9, and 48+ months. We conclude that dacarbazine can be safely and effectively given as a single dose along with dactinomycin. The possibility that this combination may be more effective than single agents in obtaining complete responses in patients with visceral disease must be explored further.

Retinoblastoma with anterior chamber extension.

Anterior chamber retinoblastoma is a rare clinical entity. The authors have reviewed the records of 1500 patients with retinoblastoma to determine the incidence and prognostic ramifications. Of 30 patients with anterior chamber involvement, 15 were noted on initial examination and 15 during observation after therapy. Despite aggressive multimodality treatment, total response was never achieved and all eyes were eventually lost. Results of pathologic examination showed ciliary body invasion, which was held accountable for the poor response to therapy. Anterior chamber retinoblastoma is a poor prognostic sign which cannot be controlled effectively with current techniques and should be considered an indication for enucleation without delay.