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.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86507
Title:
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.
Authors:
Le Cesne, A; Judson, I; Crowther, Derek; Rodenhuis, S; Keizer, H J; Van Hoesel, Q; Blay, Jean-Yves; Frisch, J; Van Glabbeke, Martine M; Hermans, C; Van Oosterom, A; Tursz, T; Verweij, J
Abstract:
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/m(2) on day 1) and ifosfamide (5 g/m(2) on day 1), or an intensified regimen (arm B), combining doxorubicin (75 mg/m(2) on day 1), the same ifosfamide dose, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim, 250 microgram/m(2) 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.
Affiliation:
Institut Gustave Roussy, Villejuif, London, United Kingdom. lecesne@igr.fr
Citation:
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, 18 (14):2676-84 J. Clin. Oncol.
Journal:
Journal of Clinical Oncology
Issue Date:
Jul-2000
URI:
http://hdl.handle.net/10541/86507
PubMed ID:
10894866
Type:
Article
Language:
en
ISSN:
0732-183X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLe Cesne, Aen
dc.contributor.authorJudson, Ien
dc.contributor.authorCrowther, Dereken
dc.contributor.authorRodenhuis, Sen
dc.contributor.authorKeizer, H Jen
dc.contributor.authorVan Hoesel, Qen
dc.contributor.authorBlay, Jean-Yvesen
dc.contributor.authorFrisch, Jen
dc.contributor.authorVan Glabbeke, Martine Men
dc.contributor.authorHermans, Cen
dc.contributor.authorVan Oosterom, Aen
dc.contributor.authorTursz, Ten
dc.contributor.authorVerweij, Jen
dc.date.accessioned2009-11-19T16:10:17Z-
dc.date.available2009-11-19T16:10:17Z-
dc.date.issued2000-07-
dc.identifier.citationRandomized 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, 18 (14):2676-84 J. Clin. Oncol.en
dc.identifier.issn0732-183X-
dc.identifier.pmid10894866-
dc.identifier.urihttp://hdl.handle.net/10541/86507-
dc.description.abstractPURPOSE: 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/m(2) on day 1) and ifosfamide (5 g/m(2) on day 1), or an intensified regimen (arm B), combining doxorubicin (75 mg/m(2) on day 1), the same ifosfamide dose, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim, 250 microgram/m(2) 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.en
dc.language.isoenen
dc.subjectLiver Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshDoxorubicin-
dc.subject.meshDrug Administration Schedule-
dc.subject.meshFemale-
dc.subject.meshGranulocyte Macrophage Colony-Stimulating Factors, Recombinant-
dc.subject.meshHumans-
dc.subject.meshIfosfamide-
dc.subject.meshLeiomyosarcoma-
dc.subject.meshLiver Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshSarcoma-
dc.subject.meshSurvival Analysis-
dc.titleRandomized 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.en
dc.typeArticleen
dc.contributor.departmentInstitut Gustave Roussy, Villejuif, London, United Kingdom. lecesne@igr.fren
dc.identifier.journalJournal of Clinical Oncologyen

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