scholarly journals Phase II Trial of Doxorubicin Plus Escalated High-Dose Ifosfamide in Patients With Advanced Soft Tissue Sarcomas of the Adult: A Study of the Spanish Group for Research on Sarcomas (GEIS)

Sarcoma ◽  
2006 ◽  
Vol 2006 ◽  
pp. 1-8 ◽  
Author(s):  
A. López-Pousa ◽  
J. Martín ◽  
J. Montalar ◽  
R. de las Peñas ◽  
J. García del Muro ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Febrile Neutropenia ◽  
Continuous Infusion ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Soft Tissue Sarcomas ◽  
High Dose ◽  
Substantial Toxicity ◽  
Grade 3

Background.To explore the tolerance and the activity of high-dose ifosfamide (IFOS) combined with doxorubicin (DXR) at 50 mg/m2every 4 weeks in patients with soft tissue sarcomas.Methods.DXR was given IV bolus and IFOS by continuous infusion at 2 g/m2/day. Initial IFOS dose (12 g/m2) was adjusted to 10, 13, or 14 g/m2according to toxicity.Results.Seventy patients received 277 cycles (median 3 cycles, range 1–10), 34% with IFOS dose increased, 30% decreased, and 48% delivered at 12 g/m2. Toxicity grade 4 occurred on granulocytes (67% of patients) or platelets (19%), 54% had febrile neutropenia, 31% grade 3/4 asthenia, and 26% abandoned the study due to toxicity. Three toxic deaths occurred. In 57 non-GIST patients objective activity was 45.6% (95% CI, 32 to 58%).Conclusion.At least 4 cycles were tolerated by 71% of patients, most receiving DXR 50 mg/m2plus IFOS 10–12 g/m2, with substantial toxicity.

High-dose ifosfamide in bone and soft tissue sarcomas: results of phase II and pilot studies--dose-response and schedule dependence.

1997 ◽  
Vol 15 (6) ◽  
pp. 2378-2384 ◽  
Author(s):  
S R Patel ◽  
S Vadhan-Raj ◽  
N Papadopolous ◽  
C Plager ◽  
M A Burgess ◽  
...  
Keyword(s):  
Pilot Study ◽  
Soft Tissue ◽  
Continuous Infusion ◽  
Phase Ii ◽  
Dose Response ◽  
Overall Response Rate ◽  
Response Rate ◽  
Soft Tissue Sarcomas ◽  
High Dose ◽  
Grade 3

PURPOSE 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. PATIENTS AND 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. CONCLUSION 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.

scholarly journals Phase II trial of first-line high-dose ifosfamide in advanced soft tissue sarcomas of the adult: A study of the Spanish Group for Research on Sarcomas (GEIS)

1998 ◽  
Vol 9 (8) ◽  
pp. 871-876 ◽  
Author(s):  
J.M. Buesa ◽  
A. López-Pousa ◽  
J. Martín ◽  
A. Antón ◽  
J. García del Muro ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Soft Tissue Sarcomas ◽  
High Dose ◽  
First Line

High-dose ifosfamide: circumvention of resistance to standard-dose ifosfamide in advanced soft tissue sarcomas.

1995 ◽  
Vol 13 (7) ◽  
pp. 1600-1608 ◽  
Author(s):  
A Le Cesne ◽  
E Antoine ◽  
M Spielmann ◽  
T Le Chevalier ◽  
E Brain ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Febrile Neutropenia ◽  
Standard Dose ◽  
Soft Tissue Sarcomas ◽  
Response Duration ◽  
High Dose ◽  
Median Response ◽  
Major Toxicity ◽  
Disease Stabilization ◽  
Grade 3

PURPOSE The study was designed to assess the toxicity and activity of high-dose ifosfamide (HDI) administered by continuous infusion at a dose of 4 g/m2/d over 3 days every 4 weeks in adult patients with advanced soft tissue sarcomas (ASTS) pretreated with doxorubicin and/or a standard-dose ifosfamide (SDI)-containing regimen. PATIENTS AND METHODS Between January 1991 and November 1993, 40 patients with progressive ASTS were entered onto the study. Twenty-eight patients had been pretreated with a multidrug regimen that contained SDI and were classified as follows: SDI-refractory (n = 21), SDI-resistant (n = 2), and indeterminate SDI-sensitive (n = 5). Patients were treated until progression or major toxicity. RESULTS One hundred forty-seven cycles of HDI were administered. Neutropenia was dose-limiting, with 100% of patients experiencing grade 3 to 4 toxicity and 12 admissions for febrile neutropenia (30% of patients). Neurotoxicity (17% of patients) was significantly associated with acute renal failure (n = 4) (P < .001), grade 4 thrombocytopenia (P < .01) and febrile neutropenia (P = .048). Chronic renal toxicity (n = 4) was significantly associated with retroperitoneal masses and/or prior nephrectomy (P = .008). Partial responses (PRs) were observed in 12 of 36 assessable patients (33%) and eight patients (22%) experienced disease stabilization. All but one response occurred in patients pretreated with SDI, with five PRs among SDI-refractory patients. Leiomyosarcomas appear resistant to HDI. The median response duration was 8 months (range, 6 to 13+) and the median overall survival time was 12 months. CONCLUSION The activity of HDI in these pretreated ASTS patients and the apparent circumvention of SDI resistance suggest a real dose-response relationship for ifosfamide and deserve further evaluation. Although toxic, this treatment appears feasible and manageable using routine clinical support. Since prophylaxis of ifosfamide-induced renal damage remains unknown, frequent monitoring of renal and tubular functions during therapy is highly recommended.

Dose-intensive chemotherapy with ifosfamide, epirubicin, and filgrastim for adult patients with metastatic or locally advanced soft tissue sarcoma: a phase II study.

1998 ◽  
Vol 16 (4) ◽  
pp. 1438-1443 ◽  
Author(s):  
P Reichardt ◽  
J Tilgner ◽  
P Hohenberger ◽  
B Dörken
Keyword(s):  
Soft Tissue ◽  
Continuous Infusion ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
High Dose ◽  
Impact On Survival ◽  
Grade 3 ◽  
Stimulating Factor ◽  
Experienced Grade

PURPOSE To evaluate the feasibility and toxicity of the combination of full-dose epirubicin (EPI) and high-dose ifosfamide (IFO) with granulocyte colony-stimulating factor (G-CSF) support and to determine the clinical efficacy in terms of response and impact on survival. PATIENTS AND METHODS Forty-six consecutive, previously untreated patients with locally advanced or metastatic high-grade soft tissue sarcomas were treated with IFO 2.5 g/m2/d as a continuous infusion on days 1 to 5 and EPI 45 mg/m2/d as a continuous infusion on days 2 and 3 every 3 weeks. G-CSF 5 microg/kg/d subcutaneously (s.c.) was given on days 6 to 15 or until recovery of leukocytes after all cycles. Response evaluation was performed every two cycles and responding patients were treated with up to six cycles. All patients were evaluated for resectability of residual local or metastatic disease and underwent surgery if possible. RESULTS All patients experienced grade 3 or 4 myelosuppression. Other toxicities were mild. The overall response rate was 52%, with a complete remission (CR) rate of 22% after chemotherapy alone. Eight additional patients were rendered free of tumor (no evidence of disease [NED]) by surgical procedures. The median overall survival of all patients is 24 months. The CR/NED patients (39%) have a significantly superior survival time compared with all other patients. Thirteen of these 18 patients (72%) are alive, nine free of tumor, with a median follow-up time of 33 months. CONCLUSION This dose-intensive combination chemotherapy is toxic but feasible and produced a high number of partial remissions (PRs) and especially CRs, which resulted in prolonged survival.

A four-arm randomized phase II trial with NGR-hTNF given at low or high dose with or without doxorubicin in soft tissue sarcomas (STS).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 10525-10525
Author(s):  
Stefano Ferrari ◽  
Paolo G Casali ◽  
Jean-Yves Blay ◽  
Axel Le Cesne ◽  
Tonini Giuseppe ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Soft Tissue Sarcomas ◽  
High Dose ◽  
Randomized Phase Ii

scholarly journals Phase II study of continuous-infusion high-dose ifosfamide in advanced and/or metastatic pretreated soft tissue sarcomas

1997 ◽  
Vol 8 (11) ◽  
pp. 1159-1162 ◽  
Author(s):  
R. Palumbo ◽  
S. Palmeri ◽  
M. Antimi ◽  
C. Gatti ◽  
P. Raffo ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Continuous Infusion ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Soft Tissue Sarcomas ◽  
High Dose

Randomized Phase III Study Comparing Conventional-Dose Doxorubicin Plus Ifosfamide Versus High-Dose Doxorubicin Plus Ifosfamide Plus Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor in Advanced Soft Tissue Sarcomas: A Trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group

2000 ◽  
Vol 18 (14) ◽  
pp. 2676-2684 ◽  
Author(s):  
A. Le Cesne ◽  
I. Judson ◽  
D. Crowther ◽  
S. Rodenhuis ◽  
H.J. Keizer ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Dose Regimen ◽  
Standard Dose ◽  
Soft Tissue Sarcomas ◽  
Dose Intensity ◽  
High Dose ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Grade 3 ◽  
Stimulating Factor

PURPOSE: This randomized multicenter study was designed to compare the activity of a high-dose doxorubicin-containing chemotherapy regimen with a conventional standard-dose regimen in adult patients with advanced soft tissue sarcomas (ASTS). PATIENTS AND METHODS: Between 1992 and 1995, 314 patients were randomized to receive a standard-dose regimen (arm A), containing doxorubicin (50 mg/m2 on day 1) and ifosfamide (5 g/m2 on day 1), or an intensified regimen (arm B), combining doxorubicin (75 mg/m2 on day 1), the same ifosfamide dose, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim, 250 μg/m2 on days 3 to 16); all courses were repeated every 3 weeks. RESULTS: The median age of the 294 eligible patients was 50 years. They received a median of five chemotherapy cycles. The median dose and relative doxorubicin dose-intensity achieved were 245 mg and 97% in arm A and 360 mg and 99% in arm B, respectively. Thirty-eight percent and 23% of patients presented with leiomyosarcomas and liver metastases, respectively. Objective responses were observed in 31 (21%) of 147 assessable patients in arm A and in 31 (23.3%) of 133 in arm B (P = .65). No change was observed in 41.6% and 46.2% of patients in arm A and B, respectively. Progression-free survival (PFS) was significantly longer in the intensive arm (P = .03). The median duration of the time to progression was 19 weeks in the conventional arm and 29 weeks in the intensified arm. There was no difference in overall survival (P = .98) between the two therapeutic arms. Toxicities were manageable in both arms. A grade 3/4 neutropenia and infection occurred in 92% and 4.6% of patients in arm A, respectively, and in 90% and 16.6% in arm B, respectively. Grade 3/4 thrombocytopenia was more frequent in arm B. CONCLUSION: The use of rhGM-CSF allowed safe escalation of chemotherapy doses. Despite a 50% increase of the doxorubicin dose-intensity, the high-dose regimen failed to demonstrate any impact on survival in patients with ASTS. The low complete response rate, the high incidence of leiomyosarcomas, and liver metastases may in part explain these results. However, the lengthening of the PFS in the intensive arm, because of the quality of stable disease and inappropriate tumor evaluation policies that potentially lead to an underestimation of antitumor activity, does not definitively refute the use of a high-dose chemotherapy regimen in selected patients with ASTS.

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