Efficacy of Sequential High-Dose Doxorubicin and Ifosfamide Compared With Standard-Dose Doxorubicin in Patients With Advanced Soft Tissue Sarcoma: An Open-Label Randomized Phase II Study of the Spanish Group for Research on Sarcomas

2009 ◽  
Vol 27 (11) ◽  
pp. 1893-1898 ◽  
Author(s):  
Joan Maurel ◽  
Antonio López-Pousa ◽  
Ramón de las Peñas ◽  
Joaquín Fra ◽  
Javier Martín ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Standard Dose ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
High Dose ◽  
Open Label ◽  
Advanced Soft Tissue Sarcoma ◽  
Ecog Performance Status

Purpose To assess the progression-free survival (PFS) and antitumor response to standard-dose doxorubicin compared with sequential dose-dense doxorubicin and ifosfamide in first-line treatment of advanced soft tissue sarcoma. Patients and Methods Patients with measurable advanced soft tissue sarcoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2, between the ages 18 and 65 years, and with adequate bone marrow, liver, and renal function were entered in the study. The stratifications were: ECOG PS (0 v 1), location of metastases, and potentially resectable disease. Patients were randomly assigned to either doxorubicin 75 mg/m2 given as a bolus injection every 3 weeks for 6 cycles (arm A) or doxorubicin at 30 mg/m2 per day for 3 consecutive days once every 2 weeks for 3 cycles followed by ifosfamide at 12.5 g/m2 delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles with filgastrim or pegfilgastrim support (arm B). Results Between December 2003 and September 2007, 132 patients were entered onto the study. Febrile neutropenia, asthenia, and mucositis were more frequent in the arm B. The interim preplanned analysis for futility allowed the premature closure. Objective responses were observed in 23.4% of assessable patients in arm A and 24.1% in arm B. PFS was 26 weeks in the arm A and 24 weeks in arm B (P = .88). Overall survival did not differ between the two therapeutic arms (P = .14). Conclusion Single-agent doxorubicin remains the standard treatment in fit patients with advanced soft tissue sarcoma.

scholarly journals A Phase II Study of Docetaxel in Chemotherapy-Naïve Patients With Recurrent or Metastatic Adult Soft Tissue Sarcoma

Sarcoma ◽  
1998 ◽  
Vol 2 (1) ◽  
pp. 29-33 ◽  
Author(s):  
Vivien Bramwell ◽  
Martin Blackstein ◽  
Karl Belanger ◽  
Shail Verma ◽  
Sandra Beare ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Haematological Toxicity ◽  
Dose Intensity ◽  
Ecog Performance Status ◽  
Metastatic Soft Tissue Sarcoma ◽  
Toxicity Criteria

Purpose:To determine the efficacy and toxicity of docetaxel as first-line chemotherapy in adult patients with locally advanced and/or metastatic soft tissue sarcoma (STS).Patients/methods.Thirty eligible patients, with histologically proven STS, Eastern Cooperative Oncology Group (ECOG) performance status 0–2 and bidimensionally measurable disease, entered this study. None had received previous chemotherapy. Docetaxel 100 mgm−2was given as a 1-h intravenous infusion every 3 weeks. Patients were evaluable for response, evaluated by WHO criteria, after one cycle of chemotherapy and toxicity was graded by NCIC-CTG common toxicity criteria.Results.One hundred and thirty two cycles were aldministered, with a range per patient of 1–9. The median delivered dose intensity was 32.2 mgm−2 week−1(planned 33.3 mgm−2 week−1) and 67% of patients received ≥90% planned dose intensity. There were three partial responses (10.7%; 95% confidence interval 2.3–28.2) with a median duration of 7 months (range 6.4–8.3 months). Thirty patients were evaluable for non-haematological toxicity and 28 for haematological toxicity (repeat counts were not available in two patients). Haematological toxicity was moderately severe, with 18 (64%) patients experiencing at least one episode of grade 4 neutropenia, and 7 (25%) patients experiencing febrile neutropenia.Conclusions.In this study, activity of docetaxel in adult chemotherapy-naïve patients with advanced STS was modest

Phase III Trial of Two Investigational Schedules of Ifosfamide Compared With Standard-Dose Doxorubicin in Advanced or Metastatic Soft Tissue Sarcoma: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study

2007 ◽  
Vol 25 (21) ◽  
pp. 3144-3150 ◽  
Author(s):  
Paul Lorigan ◽  
Jaap Verweij ◽  
Zsuzsa Papai ◽  
Sjoerd Rodenhuis ◽  
Axel Le Cesne ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Standard Dose ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Soft Tissue Sarcoma ◽  
Phase Iii Trial ◽  
Free Survival

Purpose Single-agent doxorubicin remains the standard treatment for advanced soft tissue sarcomas. Combining doxorubicin with standard-dose ifosfamide has not been shown to improve survival and is associated with a significantly increased toxicity; it is not known whether higher dose single-agent ifosfamide is superior to doxorubicin. Patients and Methods This randomized prospective multicenter phase III trial was designed to compare progression-free survival of patients with advanced soft tissue sarcoma receiving either regimen of standard doxorubicin 75 mg/m2 every 21 days, ifosfamide 9 g/m2 over 3 days continuous infusion, or ifosfamide 3 g/m2 per day in 3 hours over 3 days. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, and toxicity. Results The study included 326 patients. Grade 4 leukopenia, neutropenia, febrile neutropenia, and encephalopathy were more frequent in the ifosfamide arms. Progression-free survival, overall survival, and response rates were not significantly different between the three arms. An independent data monitoring committee reviewed the interim data and recommended early closure of the trial for futility (ie, no significant difference would be shown). Conclusion Single-agent doxorubicin remains the treatment of choice for patients with advanced soft tissue sarcoma.

Advanced soft-tissue sarcoma in patients over age 75: Patterns of care and survival.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10057-10057
Author(s):  
Delphine Garbay Decoopman ◽  
Mary Louise Keohan ◽  
Angela Cioffi ◽  
Robert G. Maki ◽  
Binh Bui Nguyen ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Systemic Therapy ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Advanced Soft Tissue Sarcoma ◽  
Optimal Care ◽  
Entire Cohort

10057 Background: There are no data regarding the management and the outcome of elderly patients (pts) diagnosed with advanced soft-tissue sarcoma (STS). Methods: The charts of pts aged ≥ 75 years and diagnosed with metastatic and/or unresectable STS between 1990 and 2011 at Memorial Sloan Kettering (New York) and Institut Bergonié (Bordeaux, France) were reviewed. Results: 189pts were included.Median age was 79 years (range 75-93).160 pts (84.5%) had metastatic disease. The most frequent histological subtype was leiomyosarcoma (n=57, 30%). The median age-adjusted Charlson comorbidity score was 10 (range 5-17). 120 pts (63.5%) received systemic therapy whereas 69 pts (36.5%) were managed with best supportive care (BSC) only. Pts who received BSC only were more likely ≥ 80 years old (58% versus 38%, p=0.01) and with performance status (PS) ≥ 2 (35% versus 14%, p=0.01). Single agent and combination therapy were delivered in 87 (72.5%) and 33 (27.5%) cases respectively. 67 pts (56%) received a 1st-line anthracycline-containing regimen. The median progression-free survival of pts treated with systemic therapy was 4 months (95% CI: 2.5-5.5). 21 pts (17.5%) had to stop 1st line treatment because of toxicity. On multivariate analysis, age ≥ 80 years, PS ≥ 2, and single-agent therapy were significantly associated with poor PFS. 51 pts received one or more further lines of therapies. At the time of analysis, 170 pts (90%) had died. 96% of deaths were related to the disease. The median OS for the entire cohort of pts was 9.6 months (95% CI: 7.3-12). The 1-year and 2-year OS rates were 43% (95% CI: 36–50), and 22% (95% CI: 16–28), respectively. The median OS of pts managed with systemic therapy and BSC were 12.5 months (95% CI: 8.4-16.6) and 5.1 months (95% CI: 3.7-6.5), respectively (p=0.02). However, on multivariate analysis, PS ≥ 2 and age-adjusted Charlson score ≥ 10 were the sole independent factors significantly associated with OS. Conclusions: A high proportion of elderly pts with advanced STS were considered unfit for chemotherapy. The OS of STS pts ≥ 75 years who were managed with systemic therapy seems similar to that of younger pts. Further efforts are needed to better define the optimal care for fit and unfit elderly pts with advanced STS.

Gemcitabine in heavily pretreated adult soft tissue sarcoma patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20524-20524 ◽  
Author(s):  
D. Schoeler ◽  
A. Kunitz ◽  
P. Reichardt
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Performance Status ◽  
Single Agent ◽  
Poor Performance ◽  
Cytotoxic Agents ◽  
Poor Performance Status ◽  
Advanced Soft Tissue Sarcoma ◽  
Undifferentiated Sarcoma ◽  
Heavily Pretreated

20524 Background: The number of effective cytotoxic agents in treatment of advanced soft tissue sarcoma (STS) is limited when patients have failed anthracyclin and ifosfamide therapy. There are inconsistent data in phase I / II studies and retrospective analyses evaluating the efficiacy of gemcitabine (G, 900mg/m2, d1+8, q3w) or combination of gemcitabine and docetaxel (GD, G: 900mg/m2, d1+8, D: 100 mg/m2, d8, q3w). Methods: Between 2002 and 2006 we retrospectively analyzed 14 females and 6 males with heavily pretreated advanced soft tissue sarcoma (1–5 pretreatments) who were treated in our department (Charité Campus Virchow-Klinikum) with G (n=10) or GD (n=10) depending on their performance status. The following histology types were represented: leiomyosarcoma (10), liposarcoma (3), MPNST (3), synovial sarcoma (2), undifferentiated sarcoma (1), malignant large cell sarcoma (1). Results: A total of 99 cycles (range 1 to 15) were applied. Best response was partial remission (PR=20%, G: n=2, GD: n=2) and was achieved in four patients, among them three leiomyosarcoma and one MPNST. In six cases disease stabilization was achieved for up to 15 month (SD=30%, G: n=2, GD: n=4). Four patients had progressive disease after 2–3 cycles of gemcitabine based therapy (PD=20%, G: n=0, GD: n=4). In another six cases only day one of the first cycle (G alone) was administered because of serious problems due to pretreatment and poor performance status (e.g. prolonged thrombopenia and neutropenia Grade IV, gemcitabine-induced vasculitis, gastrointestinal bleeding due to tumor localization, pneumonia, rapid tumor progression). Conclusions: Gemcitabine-based therapy for heavily pretreated STS patients in our retrospective analysis has a significant overall response rate. In patients considered unfit for GD combination, single agent G treatment remains an option with moderate effiacy. No significant financial relationships to disclose.

scholarly journals Performance status is the most powerful risk factor for early death among patients with advanced soft tissue sarcoma

2011 ◽  
Vol 104 (10) ◽  
pp. 1544-1550 ◽  
Author(s):  
N Penel ◽  
M V Glabbeke ◽  
S Mathoulin-Pelissier ◽  
I Judson ◽  
S Sleijfer ◽  
...  
Keyword(s):  
Risk Factor ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Performance Status ◽  
Early Death ◽  
Advanced Soft Tissue Sarcoma

scholarly journals Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial

2013 ◽  
Vol 31 (11) ◽  
pp. 1405-1414 ◽  
Author(s):  
Athanassios Argiris ◽  
Musie Ghebremichael ◽  
Jill Gilbert ◽  
Ju-Whei Lee ◽  
Kamakshi Sachidanandam ◽  
...  
Keyword(s):  
Head And Neck ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Oncology Group ◽  
Ecog Performance Status ◽  
Grade 3

Purpose We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Results Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. Conclusion The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.

scholarly journals A Phase II Nonrandomised Open-Label Study of Liposomal Daunorubicin (DaunoXome) in Advanced Soft Tissue Sarcoma

Sarcoma ◽  
2006 ◽  
Vol 2006 ◽  
pp. 1-5 ◽  
Author(s):  
Anne McTiernan ◽  
Jeremy Whelan ◽  
Michael Leahy ◽  
Penella J. Woll ◽  
Ian Judson
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Significant Activity ◽  
Open Label ◽  
Advanced Soft Tissue Sarcoma ◽  
Liposomal Daunorubicin ◽  
Open Label Study ◽  
Previously Treated ◽  
Grade 3 ◽  
Free Rate

Thirty four patients with advanced soft tissue sarcoma not previously treated with an anthracycline were treated with DaunoXome 100mg/m2 every 3 weeks. Thirty-three patients were evaluable for toxicity. Grade 3-4 neutropenia was seen in 20 patients (60.6%), complicated by febrile neutropenia in 2 (6.1%). Other grade 3 toxicities were rare. Among 32 patients assessable for response, one patient had a partial response, giving a response rate of 3.13% (95% confidence interval, 0.08–16.22%). Seven patients (21.9%) had stable disease, and 24 patients (75.0%) had disease progression. The median time to progression for all patients was 42 days (95% CI, 39–49) and the progression-free rate at 3 months was 12.5%. In conclusion, DaunoXome at this dose and schedule is well tolerated in patients with advanced soft tissue sarcoma, but is not associated with significant activity. Further studies at this dose and schedule cannot be recommended in this disease.

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