LISBON, Portugal--A new regimen that employs escalating doses of etoposide(Drug information on etoposide) (VePesid) and ifosfamide(Drug information on 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 26%.
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.