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.

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.

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 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.

Plasmablastic Lymphoma Is Curable The HAART Era. A 10 Year Retrospective By The AIDS Malignancy Consortium (AMC)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1801-1801 ◽  
Author(s):  
Ariela Noy ◽  
Amy Chadburn ◽  
Shelly Y. Lensing ◽  
Page Moore
Keyword(s):  
Initial Diagnosis ◽  
Stage I ◽  
Plasmablastic Lymphoma ◽  
High Dose ◽  
Refractory Disease ◽  
Newly Diagnosed ◽  
Grade 3 ◽  
One Year ◽  
Experienced Grade

Abstract Background The highly aggressive plasmablastic lymphoma (PBL), originally described almost exclusively in HIV+ patients, was nearly uniformly fatal in the pre-HAART era. We hypothesized that aggressive chemotherapy and HAART could result in cures. Methods We retrospectively analyzed baseline characteristics, treatment patterns and outcomes of patients (pts) with PBL treated at multiple centers within the AIDS Malignancy Consortium (AMC). HIV positivity was not required. 19 confirmed PBLs from 9 national AMC sites diagnosed between 1999 and 2008 were evaluated. Results 17/19 patients (pts) with confirmed PBL were HIV+. Data was captured at initial diagnosis on 12 pts (all HIV+) and 7 with relapsed/refractory disease (5 HIV+). HAART status at PBL initial diagnosis was 33% on, 58% off, and unknown 8%. Median CD4 count 110 (range 4-658). First line chemotherapy was given to 10/12 (83%) newly diagnosed patients with stage I/II (6) vs III/IV(6) disease. This was CHOP(4), CDE (1), EPOCH (2) and EPOCH with high dose methotrexate and zidovudine (2). Second line therapy was given to 5/7 relapsed/refractory patients with stage I (1) vs Stage III/IV (5) disease and a median CD4 83 (range 10-202): EPOCH alternate HD Mtx+AZT (n=1); Hyper-CVAD (n=2); High dose Mtx + AZT (n=1); VACOP-B(n=1). One pt underwent BEAM based autologous stem cell transplant. For both groups combined, 6 patients experienced grade 3/4 toxicity. Febrile neutropenia was the most common grade 3/4 toxicity (4 patients) followed by thrombocytopenia (3 patients). One patient with refractory disease experienced grade 5 toxicity. For the 12 newly diagnosed patients, 8 patients were alive at last follow-up and 4 had died. Median follow-up for survivors was 73 (range, 40-165) weeks. One-year survival was 66.7% (SE, 13.6). See Figure 1. For the 7 relapsed/refractory patients, 2 patients were alive at 24 and 54 weeks, and 1 was lost to follow-up. One-year survival was 53.6% (SE, 20.1%). Conclusions In the HAART era, aggressive treatment of PBL can result in significant survival times. However, determination of the superior treatment regimen could not be determined from this small patient sample. CTSU 9177 is prospectively studying PBL with EPOCH. Disclosures: No relevant conflicts of interest to declare.

Phase II study of low dose (LD) and high dose (HD) premarin in androgen independent prostate cancer (AIPC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4560-4560 ◽  
Author(s):  
M. Pomerantz ◽  
J. Manola ◽  
M. Taplin ◽  
G. Bubley ◽  
M. Inman ◽  
...  
Keyword(s):  
Warfarin Dose ◽  
High Dose ◽  
Clinical Predictors ◽  
Predictors Of Response ◽  
Psa Response ◽  
Transdermal Estradiol ◽  
Gi Toxicity ◽  
Grade 3 ◽  
Experienced Grade

4560 Background: Estrogens, including DES, transdermal estradiol, estramustine and PC-SPES, have shown antitumor activity in AIPC. We tested two doses of Premarin to determine efficacy and safety of this commonly available estrogen. Methods: Patients with progressive AIPC were eligible. Prior estrogen use, significant cardiac or thromboembolic disease, and concurrent steroids were not allowed. Patients were randomized to Premarin 1.25 mg once (LD) or 3 times (HD) daily. Prophylactic breast irradiation was encouraged and warfarin 1 mg daily was required, unless contraindicated. After the first stage of accrual, the LD arm was closed because of limited activity, while the HD arm continued to the 2nd stage. Results: 46 patients were enrolled; 17 patients were randomized to LD Premarin, 29 patients assigned to HD Premarin by randomization or direct assignment. One patient withdrew consent prior to therapy. Median follow up is 5.3 months. Median age was 69 years (range 52–86) and median PSA 84.6 ng/ml (range 2.5–794.1). 19 patients (41%) had measurable disease. PSA declines ≥ 50% were seen in 0% (95% C.I., 0–19.5) and 32.1% (95% C.I., 15.9–52.4) of patients treated with LD and HD premarin. 1 patient treated with HD Premarin had a partial measurable response (8.3%; 95% C.I., 0.2–38.5). Median time to progression was 3.3 and 3.2 months in the LD and HD arms, respectively. Premarin was well tolerated in 45 evaluable patients. One grade 4 toxicity was noted, a stroke in the LD arm. Grade 3 toxicity was rare with 1 allergic reaction, 2 DVTs and 3 episodes of GI toxicity in one patient. Two patients experienced grade 3 elevations in PT requiring modification of warfarin dose. No significant gynecomastia was reported. Analysis of serially drawn hormone levels and molecular correlates of treatment response is pending. Conclusions: HD Premarin is associated with a 32.1% PSA response rate, while no responses were seen with LD Premarin. A measurable response was noted in 1 of 12 patients treated with HD Premarin. Toxicity was modest, though thromboembolism was seen even with prophylactic warfarin. Ongoing studies are evaluating molecular and clinical predictors of response. No significant financial relationships to disclose.

Effect of adjuvant chemotherapy on survival in FNCLCC grade 3 soft tissue sarcomas: A multivariate analysis of the French Sarcoma Group database

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10504-10504
Author(s):  
A. Italiano ◽  
F. Delva ◽  
V. Brouste ◽  
P. Terrier ◽  
M. Trassard ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Adjuvant Chemotherapy ◽  
Soft Tissue ◽  
Meta Analysis ◽  
Soft Tissue Sarcomas ◽  
Tumor Grade ◽  
Grade 3 ◽  
The Impact

10504 Background: The SMAC meta-analysis failed to demonstrate that adjuvant chemotherapy (AC) significantly improves overall survival (OS) in adult patients with localised resectable soft-tissue sarcoma (STS). We report here the analysis of the impact of AC in the population of STS patients included in the prospective database of the French Sarcoma Group. Methods: Between 1980 and 1999, 2,029 pts with STS were admitted to one of the 20 tertiary cancer centers of the GSF for the management of a first tumoral event and were included prospectively in a comprehensive database. 152 pts were excluded from the study because of metastatic disease at diagnosis. All the cases were reviewed by the pathology subcommittee of the GSF. Tumor grade was assessed according to the FNCLCC system based on tumor differentiation, mitotic count, and necrosis. Results: 283 pts (14.5%) had grade 1, 736 (39.5%) grade 2 and 858 (46%) grade 3 tumors. 1,102 pts (59%) had extremity tumors. The commonest pathological subtypes were MFH 22.5%, liposarcoma 18%, leiomyosarcoma 13%, and synovial sarcoma 10%. 1,122 pts (60%) received adjuvant radiotherapy. AC was delivered in 16 grade 1 pts (6%), 167 grade 2 pts (23%) and 323 grade 3 pts (38%). The majority of patients who received AC had tumors with a deep topography (91%) and/or > 5 cm (75%) and/or located in the limbs (61%). The median follow-up was 9 years. The 5 year-OS was 90% for grade 1 pts, 63% for grade 2 pts and 46% for grade 3 pts. On multivariate analysis ( table 1 ), AC was strongly associated with improved metastasis-free survival (MFS) (5 year MFS: 53% vs 47%, HR 0.7 [0.5–0.9], p=0.003) and overall survival (OS) (5 year OS: 56% vs 44%, HR 0.7 [0.5–0.8], p=0.004) in grade 3 pts. This association was not observed in grade 2 pts (5 year MFS: 73% vs 72%, HR 0.9 [0.6–1.4], p=0.9; 5 year OS: 73% vs 65%, HR 0.7 [0.5–1.1]). Conclusions: This large cohort-based analysis with long-term follow-up indicates that FNCLCC grade 3 pts are likely to benefit from AC. [Table: see text] [Table: see text]

Phase I/II Study of Preoperative Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy in Patients With Locally Advanced Rectal Cancer: Cancer and Leukemia Group B 89901

2006 ◽  
Vol 24 (16) ◽  
pp. 2557-2562 ◽  
Author(s):  
David P. Ryan ◽  
Donna Niedzwiecki ◽  
Donna Hollis ◽  
Brent E. Mediema ◽  
Scott Wadler ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Continuous Infusion ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Rectal Adenocarcinoma ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Grade 3 ◽  
Experienced Grade

Purpose The addition of oxaliplatin to fluorouracil in patients with advanced colorectal cancer improves survival. This phase I/II study evaluated the addition of weekly oxaliplatin to preoperative continuous infusion fluorouracil (FU) and external-beam radiation therapy (RT) in patients with locally advanced rectal adenocarcinoma. Patients and Methods Patients with clinical T3/T4 rectal adenocarcinoma and no evidence of metastases were treated with weekly oxaliplatin, continuous infusion FU 200 mg/m2 intravenously, and RT. A total of 6 weekly doses of oxaliplatin were planned. RT dose was 1.8 Gy/fraction to a total dose of 50.4 Gy. In the phase I portion, oxaliplatin was escalated from 30 to 60 mg/m2. Results Forty-four patients were entered onto the study, 18 on the phase I portion and 26 on the phase II portion. The maximum-tolerated dose (MTD) for oxaliplatin was determined to be 60 mg/m2. At the MTD, 12 patients experienced grade 3 or 4 diarrhea, two patients experienced grade 3 neutropenia, and one patient experienced grade 3 thrombocytopenia. Fifty-six percent of patients entered at the MTD completed all 6 weeks of oxaliplatin. Eight (25%) of 32 patients enrolled at the phase II dose experienced a pathologic complete response. Conclusion In this multicenter study, the addition of oxaliplatin to intravenous continuous infusion FU and RT for patients with locally advanced rectal cancer was associated with a high pathologic complete response rate but more toxicity than when FU is used alone. A regimen of weekly oxaliplatin, continuous infusion FU, and radiation therapy is now being evaluated by the National Surgical Adjuvant Breast and Bowel Project.

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