PURPOSE: To define the maximum tolerated dose of etoposide phosphate when used with G-CSF in the treatment of patients with refractory malignancies. PATIENTS AND METHODS: Eleven patients with advanced cancer refractory to standard therapy were treated with etoposide phosphate given over 1-2 hours on three consecutive days. The first cohort of patients received a total dose of 1596 mg/m2 (equivalent to etoposide 1400 mg/m2); doses were escalated in subsequent patient cohorts. G-CSF 5 micrograms/kg was administered subcutaneously from day 4 until the total leukocyte count rose to > 10,000/microL. Two courses were given at 28 day intervals. RESULTS: Toxicity produced by high dose etoposide phosphate included myelosuppression and mucositis. Three of five patients treated at the 2280 mg/m2 dose level (equivalent to etoposide 2000 mg/m2) had dose limiting toxicities (grade 4 leukopenia for 7 days, 2 patients; grade 4 mucositis + leukopenia, 1 patient). In addition, median days with severe thrombocytopenia (< 50,000/microL) rose to six days at this dose. Other toxicity was uncommon. CONCLUSIONS: In pretreated patients, the maximum tolerated dose of etoposide phosphate with G-CSF is 1938 mg/m2 (equivalent to etoposide 1700 mg/m2). Dose-limiting toxicities were myelosuppression and mucositis, as with high dose etoposide. Etoposide phosphate can be substituted for etoposide in high dose regimens; due to its greater solubility, administration can be more rapid, requires less fluid volume, and is not associated with acidosis.
PURPOSE: To define the maximum tolerated dose of etoposide phosphate when used with G-CSF in the treatment of patients with refractory malignancies. PATIENTS AND METHODS: Eleven patients with advanced cancer refractory to standard therapy were treated with etoposide phosphate given over 1-2 hours on three consecutive days. The first cohort of patients received a total dose of 1596 mg/m2 (equivalent to etoposide 1400 mg/m2); doses were escalated in subsequent patient cohorts. G-CSF 5 micrograms/kg was administered subcutaneously from day 4 until the total leukocyte count rose to > 10,000/microL. Two courses were given at 28 day intervals. RESULTS:Toxicity produced by high dose etoposide phosphate included myelosuppression and mucositis. Three of five patients treated at the 2280 mg/m2 dose level (equivalent to etoposide 2000 mg/m2) had dose limiting toxicities (grade 4 leukopenia for 7 days, 2 patients; grade 4 mucositis + leukopenia, 1 patient). In addition, median days with severe thrombocytopenia (< 50,000/microL) rose to six days at this dose. Other toxicity was uncommon. CONCLUSIONS: In pretreated patients, the maximum tolerated dose of etoposide phosphate with G-CSF is 1938 mg/m2 (equivalent to etoposide 1700 mg/m2). Dose-limiting toxicities were myelosuppression and mucositis, as with high dose etoposide. Etoposide phosphate can be substituted for etoposide in high dose regimens; due to its greater solubility, administration can be more rapid, requires less fluid volume, and is not associated with acidosis.
Authors: S Z Fields; D R Budman; R R Young; W Kreis; R Ingram; P Schulman; R C Cherny; J Wright; J Behr; C Snow; L P Schacter Journal: Bone Marrow Transplant Date: 1996-11 Impact factor: 5.483
Authors: T Philip; C Guglielmi; A Hagenbeek; R Somers; H Van der Lelie; D Bron; P Sonneveld; C Gisselbrecht; J Y Cahn; J L Harousseau Journal: N Engl J Med Date: 1995-12-07 Impact factor: 91.245
Authors: M L Slevin; P I Clark; S P Joel; S Malik; R J Osborne; W M Gregory; D G Lowe; R H Reznek; P F Wrigley Journal: J Clin Oncol Date: 1989-09 Impact factor: 44.544
Authors: J D Hainsworth; N Levitan; G L Wampler; C P Belani; M S Seyedsadr; J Randolph; L P Schacter; F A Greco Journal: J Clin Oncol Date: 1995-06 Impact factor: 44.544
Authors: R A Brown; R H Herzig; S N Wolff; D Frei-Lahr; L Pineiro; B J Bolwell; J N Lowder; E A Harden; K R Hande; G P Herzig Journal: Blood Date: 1990-08-01 Impact factor: 22.113