Rechallenge with ifosfamide-containing regimen as salvage option for patients with metastatic soft tissue sarcomas progressing after multiple pretreatments.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10046-10046
Author(s):  
Mathias Hoiczyk ◽  
Petra Kuschel ◽  
Florian Grabellus ◽  
Mareike Geffken ◽  
Marit Ahrens ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Median Time ◽  
Clinical Benefit ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Dose Intensity ◽  
Line Treatment ◽  
Substantial Clinical Benefit ◽  
Disease Stabilization

10046 Background: Ifosfamide (I) is commonly used in first or second-line treatment of locally advanced or metastatic soft tissue sarcomas (STS). The clinical efficacy of a rechallenge with ifosfamide (IR) or I-containing regimen (ICR) is unclear. We conducted a retrospective analysis of our institutional database (n=1354) of pts who received IR or ICR. Methods: 66 STS pts were identified, who had received more than one I-based regimen. Ifosfamide retreatment was given in neoadjuvant (n=26), adjuvant (n=18) or metastatic settings (n=22) and most patient were pretreated with doxorubicin (D; 94%). PFS was determined from first administration of IR until disease progression, OS from R until last follow-up or death. ORR (RECIST) was assessed to determine the clinical benefit rate (CBR) defined as CR, PR plus SD. Covariates were age, gender, histology, pretreatment, dose intensity, response and toxicity. Results: Median age at time of first I was 45y (range: 17-74, 44% f 56% m). Median time from diagnosis until first ICR treatment was 4mo. Median time from first I until IR, which was given as median 3rd-line treatment (2-9 lines), was 17 mo. Histologies were 12 leiomyo-, 11 lipo- 13 pleomorphic,14 synovial, 4 rhabdomyosarcomas and 12 other subtypes. Pts received a median of I 9.6 g/m²/cycle and a median of 4 cycles. I was given as monotherapy (38%) or in combination (D: 45%, other 17%). Overall median PFS was 5mo with PFS-rates of 63% at 12 and 25% at 24 wks. Median PFS was 6 mo for ICR and 2 mo for IR. The median OS was 36 mo from time of first diagnosis of metastases or locally advanced disease. ORR was 29% for I/D combination (CBR 70%) and 12 % for I monotherapy (CBR: 52%). 22 pts received a second IR with a median of 2 cycles (27% PR; CBR:77%; 69% combinations). Most common toxicities for IR/ICR were neutropenia (42%), encephalopathy (21%) and neutropenic fever (18%). Dose reductions were necessary in 18% of pts and treatment was stopped in 8% due to toxicity. No significant cardiotoxicity was observed. Conclusions: Patients with soft tissue sarcomas who had at least disease stabilization after initial ifosfamide-based therapy may derive substantial clinical benefit from a rechallenge.

Adriamycin and Cis-Platinum as First-Line Treatment in Unresectable Locally Advanced or Metastatic Adult Soft-Tissue Sarcomas

2004 ◽  
Vol 27 (3) ◽  
pp. 307-311 ◽  
Author(s):  
Haralabos P. Kalofonos ◽  
Dimitrios Bafaloukos ◽  
Theodoros G. Kourelis ◽  
Michalis V. Karamouzis ◽  
Panagiotis Megas ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

scholarly journals A Phase II Study of Flavopiridol in Patients With Previously Untreated Advanced Soft Tissue Sarcoma

Sarcoma ◽  
2006 ◽  
Vol 2006 ◽  
pp. 1-7 ◽  
Author(s):  
Don G. Morris ◽  
Vivien H. C. Bramwell ◽  
Robert Turcotte ◽  
Alvaro T. Figueredo ◽  
Martin E. Blackstein ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Dose Intensity ◽  
Advanced Soft Tissue Sarcoma ◽  
Kaplan Meier ◽  
Treatment Responses ◽  
Grade 3

Purpose. Flavopiridol is a potent cyclin-dependent kinase (CDK) inhibitor that has preclinical activity in many tumours. This synthetic flavonoid was tested in a phase II nonrandomized, nonblinded multicentre clinical trial to determine its activity and toxicity in patients with previously untreated metastatic or locally advanced soft tissue sarcoma.Methods. A total of 18 patients with histologically confirmed nonoperable soft tissue was treated with flavopiridol administered at a dose of 50 mg/m2IV over 1 hour daily×3days every 3 weeks.Results. Eighteen patients were accrued to the study over a period of 6 months. No objective responses were noted in the seventeen evaluable patients. Eight patients (47%) exhibited stable disease after 2 cycles (median duration of 4.3 months (range 1.4–6.9 months). Kaplan-Meier estimates for 3- and 6-month progression-free survivial rates were 44 percent and 22 percent, respectively. The only grade 3 toxicities were diarrhea (N=2), nausea (N=2), gastritis (N=1), and fatigue (N=1). Ninety-four percent of patients received≥90% of the planned dose intensity, during 55 treatment cycles.Conclusions. Flavopiridol was well tolerated at the dose and schedule used in this study, however, no objective treatment responses were seen and thus our results do not support further exploration of flavopiridol as a monotherapy at this dose and schedule in soft tissue sarcomas.

scholarly journals Delayed use of eribulin in a heavily pretreated liposarcoma patient, previously misdiagnosed as leiomyosarcoma

2020 ◽  
Vol 16 (1s) ◽  
pp. 9-13 ◽  
Author(s):  
Federica Martorana ◽  
Paolo Vigneri ◽  
Livia Manzella ◽  
Elena Tirrò ◽  
Héctor J. Soto Parra
Keyword(s):  
Soft Tissue ◽  
Adverse Effects ◽  
Safety Profile ◽  
Clinical Benefit ◽  
Soft Tissue Sarcomas ◽  
Molecular Profiling ◽  
Efficacy And Safety ◽  
Substantial Clinical Benefit ◽  
Heavily Pretreated ◽  
Low Incidence

Due to its low incidence, liposarcoma displays a limited number of therapeutic options. However, eribulin recently received approval for the treatment of advanced liposarcoma patients, progressing to at least two chemotherapy lines. We report herein the case of a man initially diagnosed with a leyomiosarcoma, subsequently reclassified as a dedifferentiated liposarcoma, who received eribulin after he failed several therapy lines. Eribulin provided our patient an 8-month disease control and a substantial clinical benefit with no relevant adverse effects, showing a good efficacy and safety profile despite its delayed employ. Additionally, this case strengthens the pivotal importance of molecular profiling in the management of soft tissue sarcomas.

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.

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 205-205
Author(s):  
Daisuke Takahari ◽  
Manabu Ohashi ◽  
Atsuo Takashima ◽  
Takuro Mizukami ◽  
Naoki Ishizuka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Complete Response ◽  
Free Survival ◽  
D2 Gastrectomy ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

Flap Reconstruction of Sarcoma Defects in the Setting of Neoadjuvant and Adjuvant Radiation

2018 ◽  
Vol 35 (04) ◽  
pp. 287-293 ◽  
Author(s):  
Rohini Kadle ◽  
Catherine Motosko ◽  
George Zakhem ◽  
John Stranix ◽  
Timothy Rapp ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Soft Tissue ◽  
Radiation Treatment ◽  
Soft Tissue Sarcomas ◽  
Adjuvant Radiation ◽  
Complication Rates ◽  
Flap Reconstruction ◽  
Fasciocutaneous Flaps ◽  
Musculoskeletal Tumor Society

Background Limb-sparing treatment of extremity soft tissue sarcomas requires wide resections and radiation therapy. The resulting complex composite defects necessitate reconstructions using either muscle or fasciocutaneous flaps, often in irradiated wound beds. Methods A retrospective chart review was performed of all limb-sparing soft tissue sarcoma resections requiring immediate flap reconstruction from 2012 through 2016. Results Forty-four patients with 51 flaps were identified: 25 fasciocutaneous and 26 muscle-based flaps. Mean defect size, radiation treatment, and follow-up length were similar between groups. More often, muscle-based flaps were performed in younger patients and in the lower extremity. Seventeen flaps were exposed to neoadjuvant radiation, 12 to adjuvant radiation, 5 to both, and 17 to no radiation therapy. Regardless of radiation treatment, complication rates were comparable, with 28% in fasciocutaneous and 31% in muscle-based groups (p < 0.775). Muscle-based flaps performed within 6 weeks of undergoing radiotherapy were less likely to result in complications than those performed after greater than 6 weeks (p < 0.048). At time of follow-up, Musculoskeletal Tumor Society scores for fasciocutaneous and muscle-based reconstructions, with or without radiation, showed no significant differences between groups (mean [SD]: 91% [8%] vs. 89% [13%]). Conclusion The similar complication rates and functional outcomes in this study support the safety and efficacy of both fasciocutaneous flaps and muscle-based flaps in reconstructing limb-sparing sarcoma resection defects, with or without radiotherapy.

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