Ambulatory 4-day continuous-infusion schedule of high-dose ifosfamide with mesna uroprotection and granulocyte colony-stimulating factor in advanced solid tumours: a phase I study.
BACKGROUND
There is evidence that continuous infusion allows the delivery of higher doses of a drug while reducing the incidence of neurologic and renal toxicity. To verify prior to phase II testing the feasibility of ambulatory treatment with high-dose ifosfamide/mesna by continuous infusion in adult solid tumours, the maximum tolerated dose (MTD) and the non-haematological dose-limiting toxicities for the achievement of 2 courses of therapy were determined.


METHODS
Thirty-two patients with advanced solid tumours were given continuous-infusion ifosfamide, from 9 to 16 g/m2, over 4 consecutive days, with equidose mesna uroprotection and granulocyte colony-stimulating-factor support; courses were repeated every 3 weeks. Total dose/course was escalated by 1 g/m2, in cohorts of 3 to 5 patients until the MTD was determined.


RESULTS
At 16 g/m2, the dose-limiting toxicity was renal, with 2 of the 5 patients treated developing renal failure. Haematological toxicity was dose-related and significant at higher dosages, but generally surmountable. Ifosfamide at 15 g/m2/course with mesna uroprotection was identified as the MTD.


CONCLUSIONS
The present study shows that high-dose continuous-infusion ifosfamide, administered by portable infusion pumps, is feasible in an ambulatory regimen, with acceptable non-haematological toxicity and good patient compliance.
Toma
S
S
Department of Medical Oncology, National Institute for Cancer Research-IST, Turin, Italy.
Palumbo
R
R
Comandone
A
A
Oliva
C
C
Vincenti
M
M
Bumma
C
C
Rosso
R
R
D000328:Adult; D000368:Aged; D000553:Ambulatory Care; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D015080:Mesna / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D016896:Treatment Outcome
D007155:Immunologic Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015080:Mesna; D007069:Ifosfamide