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

Armando Santoro, Thomas Tursz, Henning Mouridsen, Jaap Verweij, Will Steward, Reiner Somers, Jose Buesa, Paolo Casali, David Spooner, Elaine Rankin, Anne Kirkpatrick, Martine Van Glabbeke, Allan Van Oosterom

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1537-1545
Number of pages9
JournalJournal of Clinical Oncology
Volume13
Issue number7
Publication statusPublished - Jul 1995

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Ifosfamide
Sarcoma
Doxorubicin
Research
Neoplasms
Therapeutics
Drug Therapy
Dacarbazine
Controlled Clinical Trials
Vincristine
Combination Drug Therapy
Tumor Burden
Cyclophosphamide
CYVADIC protocol
Confidence Intervals
Survival
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Santoro, Armando; Tursz, Thomas; Mouridsen, Henning; Verweij, Jaap; Steward, Will; Somers, Reiner; Buesa, Jose; Casali, Paolo; Spooner, David; Rankin, Elaine; Kirkpatrick, Anne; Van Glabbeke, Martine; Van Oosterom, Allan.

In: Journal of Clinical Oncology, Vol. 13, No. 7, 07.1995, p. 1537-1545.

Research output: Contribution to journalArticle

Santoro, Armando ; Tursz, Thomas ; Mouridsen, Henning ; Verweij, Jaap ; Steward, Will ; Somers, Reiner ; Buesa, Jose ; Casali, Paolo ; Spooner, David ; Rankin, Elaine ; Kirkpatrick, Anne ; Van Glabbeke, Martine ; Van Oosterom, Allan. / 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. In: Journal of Clinical Oncology. 1995 ; Vol. 13, No. 7. pp. 1537-1545.
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abstract = "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.",
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T2 - A randomized study of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group

AU - Santoro, Armando

AU - Tursz, Thomas

AU - Mouridsen, Henning

AU - Verweij, Jaap

AU - Steward, Will

AU - Somers, Reiner

AU - Buesa, Jose

AU - Casali, Paolo

AU - Spooner, David

AU - Rankin, Elaine

AU - Kirkpatrick, Anne

AU - Van Glabbeke, Martine

AU - Van Oosterom, Allan

PY - 1995/7

Y1 - 1995/7

N2 - 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.

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