1. ¹Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
2. ²Brigham and Women's Hospital Division of Gynecologic Oncology, Boston, MA 02114, USA
3. ³Dana-Farber Cancer Institute and Division of Adult Oncology, Department of Medicine and the Dana Farber/Harvard Cancer Center, Boston, MA 02114, USA
4. ⁴Department of Gynecology and Obstetrics, Massachusetts General Hospital, Boston, MA 02114, USA

Correspondence: Dr RT Penson, Massachusetts General Hospital, Cox 548, 100 Blossom Street, Boston, MA 02114, USA. E-mail: rpenson@partners.org

Received 25 February 2005; Revised 18 May 2005; Accepted 20 May 2005; Published online 28 June 2005.

Abstract

The goal of this phase I study was to develop a novel schedule using oral etoposide and infusional topotecan as a continually alternating schedule with potentially optimal reciprocal induction of the nontarget topoisomerase. The initial etoposide dose was 15 mg m^-2 b.i.d. days (D)1–5 weeks 1,3,5,7,9 and 11, escalated 5 mg per dose per dose level (DL). Topotecan in weeks 2,4,6,8,10 and 12 was administered by 96 h infusion at an initial dose of 0.2 mg m^-2 day^-1 with a dose escalation of 0.1, then at 0.05 mg m^-2 day^-1. Eligibility criteria required no organ dysfunction. Two dose reductions or delays were allowed. A total of 36 patients with a median age of 57 (22–78) years, received a median 8 (2–19) weeks of chemotherapy. At DL 6, dose-limiting toxicities consisted of grade 3 nausea, vomiting and intolerable fatigue. Three patients developed a line-related thrombosis or infection and one subsequently developed AML. There was no febrile neutropenia. There were six radiologically confirmed responses (18%) and 56% of patients demonstrated a response or stable disease, typically with only modest toxicity. Oral etoposide 35 mg m^-2 b.i.d. D1–5 and 1.8 mg m^-2 96 h (total dose) infusional topotecan D8–11 can be administered on an alternating continual weekly schedule for at least 12 weeks, with promising clinical activity.