928 Phase I trial of the topoisomerase I inhibitor GG211 as a 72-hour infusion

In a Phase I trial of the water soluble camptothecin analog GG211, 44 patients received a 72-hour infusion at doses ranging from 0.25 to 2.5 mg/m 2 /day. Myelosuppression is dose limiting. At doses ≥ 2.0 mg/m 2 /day, 6 of 14 patients experienced grade 4 granulocytopenia and 2 of 14 grade 4 thrombocytopenia. Additional side effects (≥ grade 2) included nausea, vomiting, anorexia, diarrhea, fatigue, and phlebitis. One patient at the highest dose had grade 3 mucositis in association with myelosuppression. Partial responses have been observed in ovarian, colon, and breast cancers and hepatoma. Additional minor responses have been observed in colon cancer. Whole blood GG211 lactone C SS concentrations increased linearly with dose. The mean terminal half life was 7.5 ± 3.5 hrs, and mean clearance 922 ± 292 ml/min/m 2 . Pharmacodynamic analyses demonstrated that steady-state concentrations were predictive of toxicity. Phase II studies with this novel compound are in progress.