Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies

Abstract

Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age o60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m À2 (continuous infusion for 5 days), doxorubicin 30 mg m À2 day À1 Â 3 (total dose 90 mg m À2 ), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1 -6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33 -63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade X3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

Sequential Dose-Dense Doxorubicin and Ifosfamide in Advanced Soft-Tissue Sarcoma Patients in an Out-Patient-Basis Schedule

“…Despite a high degree of grade 3/4 toxicities observed, febrile neutropenia rate was similar to that observed in the literature [ 14 ], and this occurred irrespective of the lower neutrophil threshold and less GCSF support [ 3 , 14 ]. GCSF use has been implicated in poor outcome [ 15 ].…”

“…GCSF use has been implicated in poor outcome [15]. The incidence of cardiotoxicity was not higher than that observed in the literature [3, 14]; however, a great number of thromboembolic complications may suggest that mechanical factors and changes in procoagulant systems after chemotherapy [16] might have been boosted by dose density and should be used with caution. IFO administration over 2 hours in five days may result in less renal and neurologic complications.…”

Effective Treatment of a Malignant Breast Phyllodes Tumor with Doxorubicin-Ifosfamide Therapy

“…Leyvraz et al administered a combination of high-dose ifosfamide and high-dose doxorubicin to patients with soft tissue sarcomas [8], although at different doses than those used in our study. A total of 187 chemotherapy cycles were administered, and salvage therapy was also performed.…”

Multiple cycles of PBPC-supported high-dose carboplatin and paclitaxel following mobilization with epirubicin and cisplatin are feasible but ineffective in treating patients with advanced non-small cell lung cancer

“…Epirubicin and cisplatin are largely employed in the cancer treatment of these neoplasms, so that the high-dose epirubicin and cisplatin combination might be considered in the mobilization phase of novel HDC regimens. [1][2][3][21][22][23] In our study, a mobilizing course of high-dose epirubicin and cisplatin followed by three PBPC-supported HDC courses with high doses of carboplatin and paclitaxel was associated with either a rapid hematopoietic reconstitution after each HDC course or a significant peripheral neurotoxicity at the end of treatment. Results of two phase II trials in patients with NSCLC showed that the combination of carboplatin (AUC ¼ 6) and paclitaxel (200-225 mg/m 2 ) is feasible with granulocyte CSF employed in 28-31% of courses and grade 3 peripheral neurotoxicity in 10-20%.…”