Randomized Phase II Study of Docetaxel Versus Doxorubicin in First- and Second-Line Chemotherapy for Locally Advanced or Metastatic Soft Tissue Sarcomas in Adults: A Study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group

2000 ◽  
Vol 18 (10) ◽  
pp. 2081-2086 ◽  
Author(s):  
Jaap Verweij ◽  
Siow Ming Lee ◽  
Wlodzimir Ruka ◽  
Jose Buesa ◽  
Robert Coleman ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Bone Sarcoma ◽  
Phase Iii ◽  
European Organization ◽  
Randomized Phase Ii ◽  
Docetaxel Treatment ◽  
Phase Iii Study

PURPOSE: To assess antitumor response and time to progression (TTP) with docetaxel compared with doxorubicin in first-line treatment of advanced and/or metastatic soft tissue sarcoma. PATIENTS AND METHODS: Patients with measurable soft tissue sarcoma lesions and adequate bone marrow, liver, and renal function were entered onto the study. They were randomized to either docetaxel 100 mg/m2 given as a 1-hour intravenous infusion every 3 weeks or doxorubicin 75 mg/m2 given as a bolus injection every 3 weeks. A maximum of seven cycles of treatment were scheduled. The study was designed as a randomized phase III study evaluating TTP by log-rank model. There was a clause for premature closure of the trial if fewer than five responses were observed among the first 25 assessable patients in the docetaxel treatment arm. RESULTS: Eighty-six patients were entered onto the study; 85 were assessable for toxicity and 83 for response. The rate of severe granulocytopenia was not significantly different between the two arms. Nausea (P = .001), vomiting (P < .001), and stomatitis (P = .005) were more common with doxorubicin therapy, whereas neurotoxicity was more frequent with docetaxel treatment. The response rate to doxorubicin therapy was 30% (95% confidence interval, 17% to 46%), whereas no responses to docetaxel therapy were seen (P < .001). In view of this, the trial was closed prematurely and the phase III study part was not conducted. CONCLUSION: Docetaxel is inactive in soft tissue sarcomas and cannot be recommended for further use in treatment of this disease.

Doxorubicin versus CYVADIC versus doxorubicin plus ifosfamide in first-line treatment of advanced soft tissue sarcomas: a randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group.

1995 ◽  
Vol 13 (7) ◽  
pp. 1537-1545 ◽  
Author(s):  
A Santoro ◽  
T Tursz ◽  
H Mouridsen ◽  
J Verweij ◽  
W Steward ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Response Rate ◽  
Randomized Study ◽  
Single Agent ◽  
Soft Tissue Sarcomas ◽  
Bone Sarcoma ◽  
Phase Iii ◽  
Controlled Clinical Trial ◽  
European Organization ◽  
Significant Difference

PURPOSE The aim of this trial was to compare the activity and toxicity of single-agent doxorubicin with that of two multidrug regimens in the treatment of patients with adult advanced soft tissue sarcomas. PATIENTS AND METHODS This was a prospective randomized phase III trial performed by 35 cancer centers within the Soft Tissue and Bone Sarcoma Group of the European Organization for Research and Treatment of Cancer (EORTC). Six hundred sixty-three eligible patients were randomly allocated to receive either doxorubicin 75 mg/m2 (arm A), cyclophosphamide, vincristine, doxorubicin, and dacarbazine (CYVADIC) (arm B), or ifosfamide 5 g/m2 plus doxorubicin 50 mg/m2 (arm C). RESULTS The overall response rate was 24% (95% confidence interval, 20.7% to 27.3%) among eligible patients and 26% among assessable patients. No statistically significant difference was detected among the three study arms in terms of response rate (arm A, 23.3%; arm B, 28.4%; and arm C, 28.1%), remission duration (median, 46 weeks on arm A, 48 weeks on arm B, and 44 weeks on arm C), or overall survival (median, 52 weeks on arm A, 51 weeks on arm B, and 55 weeks on arm C). The degree of myelosuppression was significantly greater for the combination of ifosfamide and doxorubicin than for the other two regimens. Cardiotoxicity was also more frequent in this arm, but other toxicities were similar. CONCLUSION In advanced soft tissue sarcomas of adults, single-agent doxorubicin is still the standard chemotherapy against which more intensive or new drug treatments should be compared. Combination chemotherapy cannot be recommended outside a controlled clinical trial with the exclusion of some subsets of sarcoma patients for whom significant tumor volume reduction may be an important end point of a chemotherapy regimen.

scholarly journals Anti-Angiogenic Agents in Management of Sarcoma Patients: Overview of Published Trials

2020 ◽  
Vol 10 ◽  
Author(s):  
Pierre-Yves Cren ◽  
Loïc Lebellec ◽  
Thomas Ryckewaert ◽  
Nicolas Penel
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Double Blind ◽  
Multikinase Inhibitors ◽  
Randomized Phase Ii ◽  
Phase Iii Trials

We reviewed all fully published clinical trials assessing anti-angiogenic agents in sarcoma patients (last issue, January 13, 2020). Anti-angiogenic macromolecules (e.g., bevacizumab or ombrabulin) provide disappointing results. Many multikinase inhibitors have been assessed with non-randomized phase II trials with limited samples and without stratification according to histological subtypes, therefore interpretation of such trials is very challenging. On the contrary, pazopanib, regorafenib, and sorafenib have been assessed using double-blind placebo-controlled randomized phase II or phase III trials. Compared to placebo, sorafenib demonstrates activity in desmoid-type fibromatosis patients. Based on results of phase 3 trial, pazopanib had obtained approval for treatment of pretreated non-adipocytic soft tissue sarcoma. Regorafenib is currently assessed in several clinical settings and provides significant improvement of progression-free survival in pre-treated non-adipocytic soft tissue sarcoma and in advanced pretreated osteosarcoma. Multikinase inhibitors are a breakthrough in sarcoma management. Many trials are ongoing. Nevertheless, predictive factors are still missing.

Combination chemotherapy using adriamycin, DTIC, cyclophosphamide, and actinomycin D for advanced soft tissue sarcomas: a randomized comparative trial. A phase III, Southwest Oncology Group Study (7613).

1987 ◽  
Vol 5 (6) ◽  
pp. 851-861 ◽  
Author(s):  
L H Baker ◽  
J Frank ◽  
G Fine ◽  
S P Balcerzak ◽  
R L Stephens ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Actinomycin D ◽  
Malignant Tumors ◽  
Soft Tissue Sarcomas ◽  
Comparative Trial ◽  
Phase Iii ◽  
Oncology Group ◽  
Southwest Oncology Group ◽  
Significant Difference

The term soft tissue sarcoma refers to a large variety of malignant tumors arising in extraskeletal connective tissues that connect, support, and surround discrete anatomic structures. All visceral organs also contain a connective stroma that can undergo malignant transformation. Because of the histological similarities of this group of tumors and their relative rarity, treatment prescriptions for patients that have disseminated disease are most often uniform. In this study, we asked the question whether adding a third drug (cyclophosphamide or actinomycin D) to Adriamycin (Adr [Adria Laboratories, Columbus, OH])-(3,3-dimethyl-1-triazeno)- imidazole-4-carboxamide (DTIC) would improve the response rate and/or survival. A unique feature of this cooperative group clinical trial was the mandatory pathology review of the histological material. All patients of the Southwest Oncology Group between June 1, 1976, and November 17, 1979, who had a biopsy-confirmed diagnosis of a soft tissue sarcoma with convincing clinical or biopsy-documented evidence of metastatic disease were eligible for the study. Patients were randomized to receive (1) Adr, 60 mg/m2 intravenously, day 1, and DTIC, 250 mg/m2 every 3 weeks (104 patients); (2) Adr and DTIC as in (1) and cyclophosphamide, 500 mg/m2, day 1 (112 patients); or (3) Adr and DTIC as in (1) and actinomycin D, 1.2 mg/m2, day 1, (119 patients). There was no statistically significant difference in response rates (33%, 34%, and 24%) (P = .25). Median durations of response were 31 weeks in the Adr-DTIC arm, 26 weeks in the cyclophosphamide-DTIC-Adr arm, and 23 weeks in the Adr-DTIC-Actinomycin D arm (P = .78). Median durations of survival were 37, 42, and 50 weeks, respectively. Again, no statistically significant differences were observed (P = .59). Toxicities from each of these treatment arms were formidable and were equivalent. Prognostic factor analysis showed a prognosis based on bone marrow reserve, sex, and pathology subtype favorable to patients.

scholarly journals European Organization for Research and Treatment of Cancer – Breast Cancer Group (EORTC BCG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 110-130
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Operable Breast Cancer ◽  
Phase Iii ◽  
European Organization ◽  
Node Negative ◽  
Cancer Group ◽  
Cancer Breast ◽  
Breast Cancer Group ◽  
Phase Iii Study

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by European Organization for Research and Treatment of Cancer – Breast Cancer Group (EORTC BCG). Clinical trials include: Postoperative adjuvant chemotherapy followed by adjuvant tamoxifen versus nil for node-negative and node-positive patients with operable breast cancer. EORTC Study No. 10901Randomized phase III study comparing short, intensive preoperative combination chemotherapy with similar therapy given postoperatively. EORTC Trial No. 10902Phase III randomized trial investigating the role of internal mammary and medial supraclavicular (IM-MS) lymph node chain irradiation in stage I–III breast cancer (joint study of the EORTC Radiotherapy Cooperative Group and the EORTC Breast Cancer Cooperative Group). EORTC Study No. 10925/22922A survey of the Breast International Group (BIG) to assess the attitude of patients aged <35 years, with early breast cancer, toward the risk of loss of fertility related to adjuvant therapies. BIG 3-98/EORTC 10002LAMANOMA: Conservative local treatment versus mastectomy after induction chemotherapy in locally advanced breast cancer: a randomized phase III study. BIG 2-00/EORTC Study No. 10974/22002p53 study: First prospective intergroup translational research trial assessing the potential predictive value of p53 using a functional assay in yeast in patients with locally advanced/inflammatory or large operable breast cancer, prospectively randomized to a taxane versus non-taxane regimen. BIG 1-00/EORTC 10994After mapping of the axilla: radiotherapy or surgery AMAROS. EORTC 10981/22023A randomized phase II–III trial evaluating the efficacy of capecitabine and vinorelbine in anthracycline and taxane pretreated metastatic breast cancer. EORTC 10001/160010Phase I study of lonafarnib (SCH 66336) in combination with Herceptin plus paclitaxel in HER-2 neu overexpressing breast cancer. EORTC 10051/16023MINDACT trial: A prospective, randomized study comparing the Amsterdam 70-gene expression signature (Mammaprint) with common clinical pathological criteria in selecting patients for adjuvant chemotherapy in node-negative breast cancer. BIG 3-04/EORTC 10041

Randomized phase II trial of concomitant CT/RT versus TPF followed by concomitant CT/RT in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5518-5518 ◽  
Author(s):  
A. Paccagnella ◽  
A. Buffoli ◽  
H. Koussis ◽  
P. D’Amanzo ◽  
L. Loreggian ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Locally Advanced ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Randomized Phase Ii ◽  
Phase Iii Study ◽  
The Difference ◽  
Grade 3 ◽  
Toxicity Pattern ◽  
Pathological Cr

5518 Background: Concomitant CT/RT is the standard treatment for LASCCHN. Induction chemotherapy followed by CT/RT vs CT/RT alone have not yet been compared. The feasibility of TPF followed by CT/RT has been evaluated in a previous study (Int J Rad Oncol Biol Phys 2004, 59:481). Methods: Pts with inoperable stage III-IVa, PS 0–1, were randomized to CT/RT [2 cycles of Cisplatin 20 mg/sqm days 1–4, 5FU 800 mg/sqm 96 hours c.i. weeks 1 and 6 during RT (66–70 Gy)] (Arm A) or 3 cycles of neoadjuvant TPF (Docetaxel 75mg/sqm day1, Cisplatin 80mg/sqm day1, 5FU 800mg/sqm 96 hours c.i) followed by the same CT/RT (Arm B). Pts were stratified according to tumor site, T stage and nodal status. Neck dissection was performed in N2-N3 patients with pathological CR on primary tumor. The planned sample size was 96 pts to detect a difference in CR (primary endpoint) up to 15% in favour of arm B. The radiological responses were evaluated by an internal committee according to RECIST criteria. Results: Preliminary data are available for 84/96 randomized pts (42 arm A, 42 arm B). Pts/tumor characteristics are well balanced in the two arms. Toxicities during induction TPF consisted primarily of G3–4 granulocytopenia 56% (febrile neutropenia: 7.5%). Grade 3–4 toxicities during CT/RT in arm A and B were mucositis (42% and 26%), dysphagia (20% and 9%), skin reaction (12% and 8.6%), asthenia (5% and 3%); G3 weight loss (2% and 3%), G3 dry-mouth (0% and 3%). Duration of CT/RT was equivalent: 6.1 wks (4.2–8.7) in arm A and 6.3 wks (3.8–9.5) in arm B. At the end of CT/RT, in the 82 pts evaluable for efficacy, radiological CR were 20% (95% CI 8–37%) in arm A and 64% (95% CI 45–80%) in arm B. Conclusions: Three cycles of neoadjuvant TPF are feasible and don’t compromise subsequent concomitant CT/RT with comparable toxicity pattern. At the end of the treatment sequence serious adverse events were 31% in arm A and 34% in arm B. The difference in CR of 40% in favour of arm B justifies the following phase III study. Final results including pCR and DFS will be presented at the meeting. [Table: see text]

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