TOXICITY AND EFFICACY OF ESCALATING DOSAGES OF RECOMBINANT HUMAN INTERLEUKIN-6 AFTER CHEMOTHERAPY IN PATIENTS WITH BREAST-CANCER OR NON-SMALL-CELL LUNG-CANCER

Purpose: To evaluate the safety, tolerability, and efficacy varying doses of recombinant human interleukin -6 (rhIL-6) after chemotherapy,

Patients and Methods: In this phase I/II study, 19 breast (stage III to IV) or non-small-cell lung cancer (NSCLC) patients received mitoxantrone (10 mg/m(2)) and thiotepa (40 mg/m(2)) every 3 weeks, followed by rhIL-6 subcutaneously (days 5 to 15) at six dose levels: 0.5, 1.0, 2.5, 5.0, 10.0, and 20.0 mu g/kg body weight/d (mu g/kg/d), rhIL-6 was increased to the next level in the individual patient in case of incomplete bone marrow recovery (leukocyte count <3 x 10(9)/L and/or platelet count <100 x 10(9)/L at day 22) and/or platelet nadir less than 25 x 10(9)/L in two consecutive cycles.

Results: Flu-like symptoms were observed in most of the patients. Nausea and vomiting were reported in seven of 48 and 19 of 48 cycles, respectively, Dose-limiting toxicity at 20.0 mu g/kg/d of rhIL-6 consisted of World Health Organization (WHO) grade 3 to 4 fly-like symptoms, nausea, and vomiting, Platelet recovery was faster in cycle 1 at 10.0 and 20.0 mu g/kg/d of rhIL-6 than at lower dose levels (P <.05); thrombocytopenia grade 4 was observed at most levels. However, only two patients needed platelet transfusions (1.0 and 2.5 mu g/kg/d rhIL-6), rhIL-6 effects on leukocytes were not dose-related, with a trend for the neutrophil nadir to increase with rhIL-6 up to 10 mu g/kg/d, rhIL-6 dose escalation did not affect hematologic parameters and chemotherapy cycle duration. Hemoglobin (P <.001) and cholesterol (P <.05) levels decreased, while acute-phase proteins increased,

Conclusion: rhIL-6 following chemotherapy is tolerable up to 10 mu g/kg/d; flu-like symptoms and nausea were dose-limiting at 20 mu g/kg/d Platelet nadir did not differ for the various rhIL-6 doses, However, a faster platelet recovery was observed at 10.0 and 20.0 mu g/kg/d of rhIL-6. (C) 1995 by American Society of Clinical Oncology.