Ifosfamide and continuous infusion etoposide in advanced adult soft tissue sarcoma. A Scandinavian sarcoma group phase II study

• Published in: European journal of cancer (1990) Vol. 33; no. 10; pp. 1551 - 1558
• Main Authors: Sæter, G., Alvegård, T.A., Monge, O.R., Strander, H., Turesson, I., Klepp, R., Söderberg, M., Wist, E., Raabe, N., Erlanson, M., Solheim, Ø.P., Hannisdal, E.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-09-1997; Elsevier
• Subjects: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Child; Combined Modality Therapy; Diseases of the osteoarticular system; dose intensity; Dose-Response Relationship, Drug; Drug Administration Schedule; etoposide; Etoposide - administration & dosage; Female; Filgrastim; Granulocyte Colony-Stimulating Factor - therapeutic use; Humans; ifosfamide; Ifosfamide - administration & dosage; Infusions, Intravenous; Male; Medical sciences; metastasectomy; Middle Aged; phase specificity; Recombinant Proteins - therapeutic use; response; Sarcoma - drug therapy; Sarcoma - secondary; Sarcoma - surgery; Soft Tissue Neoplasms - drug therapy; Soft Tissue Neoplasms - surgery; soft tissue sarcoma; Survival Rate; Treatment Outcome; Tumors of striated muscle and skeleton; Scandinavia; Europe; ifosfamide; phase specificity; metastasectomy; response; filgrastim; etoposide; dose intensity; soft tissue sarcoma; Antineoplastic agent; Human; Sarcoma; Ifosfamide; Toxicity; Treatment efficiency; Diseases of the osteoarticular system; Enzyme inhibitor; Etoposide; Malignant tumor; Dose activity relation; Podophyllotoxine derivatives; Alkylating agent; Oxazaphosphinane derivatives; Nitrogen mustard; Phase II trial; Soft tissue; Antimitotic
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/S0959-8049(97)00102-0

The purpose of this study was to evaluate tumour response and toxicity to ifosfamide and continuous infusion etoposide in metastatic or locally advanced soft tissue sarcoma, with dose escalations under G-CSF (granulocyte colony-stimulating factor) support. Of 92 eligible patients (median age 51 years), 85% had tumours of high-grade malignancy and 82% had metastatic disease. Chemotherapy, the baseline dose, consisted of etoposide 600 mg/m
2 as a 72 h infusion and ifosfamide 1500 mg/ m
2/day for 3 days, followed by G-CSF support (VIG regimen). Stepwise 10% dose escalations were performed depending on haematological toxicity. For patients considered operable after induction chemotherapy, surgical resection of all identifiable residual tumour was attempted. Complete and partial response rates were 11% and 31%, for an overall response rate of 42% (95% CI 31–52%). Forty-eight per cent of courses were dose escalated by a median of 20%. Complete responders had significantly higher, and patients with progressive disease had significantly lower, dose levels than other patients. None of 20 patients with liver métastases responded despite high dose levels. Compared to a preceding pilot study, the addition of G-CSF led to significantly higher dose levels, improved schedule adherence and less haematological toxicity, but no apparent increase in response rate. In view of the modest dose of ifosfamide applied in this study, it is possible that the prolonged infusion of etoposide made a significant contribution to the regimen's antitumour activity, although this can only be determined definitively in a randomised study.