High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence.
OBJECTIVE
To evaluate the efficacy and feasibility of high-dose ifosfamide (HDI) at a total dose of 14 g/m2 per cycle with mesna in combination with granulocyte colony-stimulating factor (G-CSF) in adult patients with sarcomas.


METHODS
Between July 1991 and February 1994, 74 patients with sarcomas (37 bone and 37 soft tissue) were treated on two simultaneous phase II studies that evaluated HDI given as a continuous infusion over 74 hours. G-CSF was started on day 5 at 5 microg/kg/d until recovery of granulocyte count. Additionally, between March 1993 and March 1994, 15 similar patients with previously treated bone or soft tissue sarcomas were treated on a pilot study in which the same total dose of ifosfamide was administered by a bolus schedule, along with mesna and G-CSF. Patients were treated until maximal response, and where possible, surgical resection of gross disease was performed.


RESULTS
Seventy-two patients from the phase II study using continuous infusion are assessable for response. Four complete responses (CRs) and 17 partial responses (PRs) were noted, for an overall response rate of 29% (95% confidence interval [CI], 19% to 39%). The response rate was 40% (95% CI, 24% to 56%) for bone sarcomas and 19% (95% CI, 6% to 32%) for soft tissue sarcomas. Fourteen patients from the pilot study that used a bolus schedule are assessable for response. One CR and seven PRs were noted, for an overall response rate of 57% (95% CI, 31% to 83%) and a response rate of 45% for soft tissue sarcomas. Two patients developed grade 3 to 4 renal toxicity, three developed grade 3 CNS toxicity, one had possible grade 3 cardiac toxicity, and two developed severe painful peripheral neuropathy. There were no treatment-related deaths.


CONCLUSIONS
HDI at 14 g/m2 with mesna and G-CSF is an active salvage regimen for patients with bone and soft tissue sarcomas. There is a definite positive dose-response curve, and bolus administration appears to be more active than continuous infusion.
Patel
S R
SR
The Sarcoma Center, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. shreyaskumar_patel@mel_sarc.mda.uth.tmc.edu
Vadhan-Raj
S
S
Papadopolous
N
N
Plager
C
C
Burgess
M A
MA
Hays
C
C
Benjamin
R S
RS
D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D015080:Mesna / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D012509:Sarcoma / Q000188:drug therapy*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D016179:Granulocyte Colony-Stimulating Factor; D015080:Mesna; D007069:Ifosfamide