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.
Penson
R T
RT
Division of Hematology and Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. rpenson@partners.org
Seiden
M V
MV
Matulonis
U A
UA
Appleman
L J
LJ
Fuller
A F
AF
Goodman
A
A
Campos
S M
SM
Clark
J W
JW
Roche
M
M
Eder
J P
JP
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