LISBON, Portugal--A new regimen that employs escalating doses
of etoposide (VePesid) and ifosfamide (Ifex), together with G-CSF
(Neupogen), appears to be among the most active combinations tested
to date in adult soft-tissue sarcoma, according to a report from
the Scandinavian Sarcoma Group.
The key to success with the so-called VIG regimen, said Dr. G.
Saeter of the Norwegian Radium Hospital, Oslo, is to take advantage
of the phase-specificity of etoposide by giving the drug as a
3-day continuous infusion rather than as a bolus. "We believe
that etoposide is an underrated drug in soft-tissue sarcoma, which
has previously been used incorrectly," Dr. Saeter said at
the European Society of Medical Oncology congress.
In this prospective phase II study, more than 90 patients with
histologically proven sarcomas, most of whom had metastatic disease,
received etoposide, 600 mg/m² over 72 hours, and ifosfamide,
1,500 mg/m²/day for 3 days, every 3 weeks, along with G-CSF,
5 mcg/kg on days 4 through 15. The protocol allowed for successive
10% dose escalations, up to a maximum of 130%, provided that white
blood cell nadirs were greater than 1.5 and platelet nadirs were
greater than 70 at defined time points.
Response Rate of 42%
The VIG regimen elicited a total response rate of 42%, with a
median duration of response of 8.5 months in patients who did
not undergo surgery. "Interestingly, we saw no responses
among patients with liver disease, but when we looked at patients
with high-grade lesions outside the liver, the total response
rate was 62%," Dr. Saeter said. Overall 3-year survival was
Relative to earlier studies that did not use growth factor, G-CSF
drastically reduced the incidence of grade IV neutropenia and
neutropenic fever. "We were able to escalate the dose in
half of the courses, as compared with 13% of courses in a pilot
study," Dr. Saeter said.