Feasibility and low toxicity of early radiotherapy after high-dose chemotherapy and autologous stem cell transplantation for patients with high-risk stage II-III and locally advanced breast carcinoma.

BACKGROUND: This prospective trial examined the feasibility, toxicity, and effectiveness of early locoregional radiotherapy after high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk American Joint Committee on Cancer (AJCC) Stage II-III and locally advanced breast carcinoma. METHODS: One hundred forty-seven consecutive patients with high-risk and locally advanced breast carcinoma were included in the current study. All patients received induction chemotherapy with a doxorubicin-based therapy, which was consolidated with high-dose cyclophosphamide, carboplatin, and thiotepa followed by autologous stem cell support. Within 50 days of the transplant, the patients were treated with locoregional radiotherapy that included the chest wall or breast, the axilla and supraclavicular area, and the internal mammary chain. The volume of lung included in the treatment volume was kept to a minimum. The central lung distance of the tangential fields ranged from 0.6-2.0 cm (mean, 1.1 cm). Tamoxifen was given based on receptor status. RESULTS: One hundred forty-six of 147 patients received the planned treatment. Only six patients had a delay in the initiation of radiotherapy, and another 16 patients had delays during radiotherapy. Leukocyte and platelet toxicities during radiotherapy were not life-threatening and blood counts thereafter returned to normal. Grade 2 (according to National Cancer Institute Common Toxicity Criteria) skin toxicity occurred in 22% of patients and Grade 3 skin toxicity occurred in 6% of patients. Radiation pneumonitis was reported to occur in 5 patients (< 4%). After a median follow-up of 36 months from diagnosis (range, 6-64 months), there were no long-term organ toxicity and no secondary malignancy reported. No treatment-related deaths were reported. Three patients (< 3%) developed locoregional recurrence. CONCLUSIONS: Locoregional radiotherapy after high-dose chemotherapy and autologous stem cell transplantation appears to be feasible and can be delivered safely within 10 weeks of transplantation. The short-term and long-term toxicity are reported to be low, with good local control.

Immunologic effects of AS101 in the treatment of cancer patients.

AS101 [ammonium trichloro(O,O'-dioxyethylene)tellurate] is a new immunomodulator previously shown to stimulate the production of different cytokines in vitro and in vivo. We report here our results of a phase I clinical trial conducted on 47 cancer patients with advanced malignancies. AS101 was administered intravenously at escalating doses from 1 to 10 mg/m2, twice or thrice a week. The maximal tolerated dose has not yet been determined. However, significant immunologic responses were noted at dose levels of 1-3 mg/m2 administered three times a week. At these doses statistically significant rises in gamma-interferon, natural killer cell activity, tumor necrosis factor and interleukin-2 (IL-2) levels as well as the expression of IL-2 receptors were noted. In most of the immunologic parameters the maximal response was seen at 3 mg/m2. Throughout the study toxicity was minimal. In view of these results phase II studies are currently being initiated.