High-dose ifosfamide with mesna and granulocyte-colony-stimulating factor (recombinant human G-CSF) in patients with unresectable malignant mesothelioma.
BACKGROUND
The current study was conducted to assess the activity and toxicity of high-dose ifosfamide and mesna with recombinant human granulocyte-colony-stimulating factor (rhG-CSF), given in an outpatient setting, in the treatment of patients with unresectable malignant mesothelioma.


METHODS
Between September 1994 and September 1996, 41 patients with histologically verified, unresectable malignant mesothelioma were registered, 38 of whom were analyzable (2 were ineligible and 1 was nonanalyzable). Patients received intravenous ifosfamide at a dose of 2.8 g/m2 over 3 hours (total dose of 14 g/m2), plus mesna at a dose of 0.56 g/m2 prior to and at 4 hours and 8 hours after ifosfamide infusion daily for 5 days every 21 days. rhG-CSF at a dose of 5 microg/kg/day was administered subcutaneously on days 6-15.


RESULTS
Response assessment could be determined adequately in 21 patients. Two patients obtained responses; 1 was a confirmed partial response (3%; 95% confidence interval [95% CI], 0-14%) and 1 was an unconfirmed response (3%; 95% CI, 5-14%). Eleven patients had stable disease (29%), 7 patients developed disease progression (18%), 1 patient had an early death (3%), and 17 patients had inadequate assessment (45%). At the time of last follow-up, 36 of the 38 eligible patients had developed disease progression, with a median progression-free survival of 5 months (95% CI, 3-7 months) and 34 patients had died with a median survival of 7 months (95% CI, 6-9 months). Twenty-four patients (63%) and 7 patients (18%), respectively, had Grade (according to Southwestern Oncology Group Toxicity Criteria) 4 hematologic toxicities and Grade 4 nonhematological toxicities. There was one treatment-related death, the result of infection, pulmonary edema, and renal failure.


CONCLUSIONS
This regimen demonstrated a low overall objective response rate with substantial toxicity, and in the opinion of the authors does not warrant further investigation in the treatment of patients with unresectable malignant mesothelioma.
Talbot
Susan M
SM
Division of Medical Oncology, Columbia University, College of Physicians and Surgeons, New York, New York, USA.
Rankin
Cathryn
C
Taub
Robert N
RN
Balcerzak
Stanley P
SP
Bhoopalam
Nirmala
N
Chapman
Robert A
RA
Baker
Laurence H
LH
Middleman
Edward L
EL
Antman
Karen H
KH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D015080:Mesna / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008654:Mesothelioma / Q000188:drug therapy*; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy*; D020011:Protective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D020011:Protective Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D015080:Mesna; D007069:Ifosfamide