A phase I clinical trial of continual alternating etoposide and topotecan in refractory solid tumours.
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.
Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. rpenson@partners.org
R T
RT
Penson
M V
MV
Seiden
U A
UA
Matulonis
L J
LJ
Appleman
A F
AF
Fuller
A
A
Goodman
S M
SM
Campos
J W
JW
Clark
M
M
Roche
J P
JP
Eder
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D019772:Topotecan / Q000008:administration & dosage
D005047:Etoposide; D019772:Topotecan