Journal of Clinical Oncology, Vol 13, 1537-1545, Copyright © 1995 by American Society of Clinical Oncology

ARTICLES

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

A Santoro, T Tursz, H Mouridsen, J Verweij, W Steward, R Somers, J Buesa, P Casali, D Spooner and E Rankin
Divisione Oncologia Medica A, Istituto Nazionale Tumori, Milano, Italy.

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.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				F. Grosso, R. Sanfilippo, E. Virdis, C. Piovesan, P. Collini, P. Dileo, C. Morosi, J. C. Tercero, J. Jimeno, M. D'Incalci, et al. Trabectedin in myxoid liposarcomas (MLS): a long-term analysis of a single-institution series Ann. Onc., May 22, 2009; (2009) mdp004v1. [Abstract] [Full Text] [PDF]

				J. Maurel, A. Lopez-Pousa, R. de las Penas, J. Fra, J. Martin, J. Cruz, A. Casado, A. Poveda, J. Martinez-Trufero, C. Balana, et al. Efficacy of Sequential High-Dose Doxorubicin and Ifosfamide Compared With Standard-Dose Doxorubicin in Patients With Advanced Soft Tissue Sarcoma: An Open-Label Randomized Phase II Study of the Spanish Group for Research on Sarcomas J. Clin. Oncol., April 10, 2009; 27(11): 1893 - 1898. [Abstract] [Full Text] [PDF]

				J.-Y. Blay, M. von Mehren, B. L. Samuels, M. P. Fanucchi, I. Ray-Coquard, B. Buckley, L. Gilles, C. Lebedinsky, Y. A. Elsayed, and A. Le Cesne Phase I Combination Study of Trabectedin and Doxorubicin in Patients with Soft-Tissue Sarcoma Clin. Cancer Res., October 15, 2008; 14(20): 6656 - 6662. [Abstract] [Full Text] [PDF]

				P. G. Casali Clinical Decision-making in Rare Tumors: What Is Needed from Clinical Trials ASCO Educational Book, January 1, 2008; 2008(1): 530 - 533. [Abstract] [Full Text] [PDF]

				K. M. Skubitz and D. R. D'Adamo Sarcoma Mayo Clin. Proc., November 1, 2007; 82(11): 1409 - 1432. [Abstract] [Full Text] [PDF]

				M. Tascilar, W. J. Loos, C. Seynaeve, J. Verweij, and S. Sleijfer The Pharmacologic Basis of Ifosfamide Use in Adult Patients with Advanced Soft Tissue Sarcomas Oncologist, November 1, 2007; 12(11): 1351 - 1360. [Abstract] [Full Text] [PDF]

				M. A. F. Hegazy, S. Z. Kotb, H. Sakr, E. El Dosoky, T. Amer, R. A. F. Hegazi, and O. Farouk Preoperative Isolated Limb Infusion of Doxorubicin and External Irradiation for Limb-Threatening Soft Tissue Sarcomas Ann. Surg. Oncol., February 1, 2007; 14(2): 568 - 576. [Abstract] [Full Text] [PDF]

				F. P. Worden, J. M.G. Taylor, J. S. Biermann, V. K. Sondak, K. M. Leu, R. Chugh, C. J. McGinn, M. M. Zalupski, and L. H. Baker Randomized Phase II Evaluation of 6 g/m2 of Ifosfamide Plus Doxorubicin and Granulocyte Colony-Stimulating Factor (G-CSF) Compared With 12 g/m2 of Ifosfamide Plus Doxorubicin and G-CSF in the Treatment of Poor-Prognosis Soft Tissue Sarcoma J. Clin. Oncol., January 1, 2005; 23(1): 105 - 112. [Abstract] [Full Text] [PDF]

				K. M. Leu, L. J. Ostruszka, D. Shewach, M. Zalupski, V. Sondak, J. S. Biermann, J. S.-J. Lee, C. Couwlier, K. Palazzolo, and L. H. Baker Laboratory and Clinical Evidence of Synergistic Cytotoxicity of Sequential Treament With Gemcitabine Followed by Docetaxel in the Treatment of Sarcoma J. Clin. Oncol., May 1, 2004; 22(9): 1706 - 1712. [Abstract] [Full Text] [PDF]

				R. Garcia-Carbonero, J.G. Supko, J. Manola, M.V. Seiden, D. Harmon, D.P. Ryan, M.T. Quigley, P. Merriam, J. Canniff, G. Goss, et al. Phase II and Pharmacokinetic Study of Ecteinascidin 743 in Patients With Progressive Sarcomas of Soft Tissues Refractory to Chemotherapy J. Clin. Oncol., April 15, 2004; 22(8): 1480 - 1490. [Abstract] [Full Text] [PDF]

				A. Yovine, M. Riofrio, J.Y. Blay, E. Brain, J. Alexandre, C. Kahatt, A. Taamma, J. Jimeno, C. Martin, Y. Salhi, et al. Phase II Study of Ecteinascidin-743 in Advanced Pretreated Soft Tissue Sarcoma Patients J. Clin. Oncol., March 1, 2004; 22(5): 890 - 899. [Abstract] [Full Text] [PDF]

				E. C. Borden, L. H. Baker, R. S. Bell, V. Bramwell, G. D. Demetri, B. L. Eisenberg, C. D. M. Fletcher, J. A. Fletcher, M. Ladanyi, P. Meltzer, et al. Soft Tissue Sarcomas of Adults: State of the Translational Science Clin. Cancer Res., June 1, 2003; 9(6): 1941 - 1956. [Abstract] [Full Text] [PDF]

				T. A. Damron, C. P. Beauchamp, B. T. Rougraff, and W. G. Ward Soft-Tissue Lumps and Bumps J. Bone Joint Surg. Am., May 28, 2003; 85(6): 1142 - 1155. [Full Text] [PDF]

				A. I. Spira and D. S. Ettinger The Use of Chemotherapy in Soft-Tissue Sarcomas Oncologist, August 1, 2002; 7(4): 348 - 359. [Abstract] [Full Text] [PDF]

				M. Lopez, P. Vici, L. Di Lauro, and S. Carpano Increasing Single Epirubicin Doses in Advanced Soft Tissue Sarcomas J. Clin. Oncol., March 1, 2002; 20(5): 1329 - 1334. [Abstract] [Full Text] [PDF]

				R. E. Ferner and D. H. Gutmann International Consensus Statement on Malignant Peripheral Nerve Sheath Tumors in Neurofibromatosis 1 Cancer Res., March 1, 2002; 62(5): 1573 - 1577. [Abstract] [Full Text] [PDF]

				V. H. C. Bramwell, D. Morris, D. S. Ernst, I. Hings, M. Blackstein, P. M. Venner, E. I. Ette, M. W. Harding, A. Waxman, and G. D. Demetri Safety and Efficacy of the Multidrug-Resistance Inhibitor Biricodar (VX-710) with Concurrent Doxorubicin in Patients with Anthracycline-resistant Advanced Soft Tissue Sarcoma Clin. Cancer Res., February 1, 2002; 8(2): 383 - 393. [Abstract] [Full Text] [PDF]

				S. Delaloge, A. Yovine, A. Taamma, M. Riofrio, E. Brain, E. Raymond, P. Cottu, F. Goldwasser, J. Jimeno, J. L. Misset, et al. Ecteinascidin-743: A Marine-Derived Compound in Advanced, Pretreated Sarcoma Patients--Preliminary Evidence of Activity J. Clin. Oncol., March 1, 2001; 19(5): 1248 - 1255. [Abstract] [Full Text] [PDF]

				A. J. Spillane, R. A'Hern, I. R. Judson, C. Fisher, and J. M. Thomas Synovial Sarcoma: A Clinicopathologic, Staging, and Prognostic Assessment J. Clin. Oncol., November 15, 2000; 18(22): 3794 - 3803. [Abstract] [Full Text] [PDF]

				J-Y. Blay, D. Bouhour, I. Ray-Coquard, C. Dumontet, T. Philip, and P. Biron High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation for Advanced Soft Tissue Sarcoma in Adults J. Clin. Oncol., November 1, 2000; 18(21): 3643 - 3650. [Abstract] [Full Text] [PDF]

				B. E. C. Plaat, H. Hollema, W. M. Molenaar, G. H. T. Broers, J. Pijpe, M. F. Mastik, H. J. Hoekstra, E. van den Berg, R. J. Scheper, and W. T. A. van der Graaf Soft Tissue Leiomyosarcomas and Malignant Gastrointestinal Stromal Tumors: Differences in Clinical Outcome and Expression of Multidrug Resistance Proteins J. Clin. Oncol., September 18, 2000; 18(18): 3211 - 3220. [Abstract] [Full Text] [PDF]

				A. Le Cesne, I. Judson, D. Crowther, S. Rodenhuis, H. J. Keizer, Q. Van Hoesel, J. Y. Blay, J. Frisch, M. Van Glabbeke, C. Hermans, et al. 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 J. Clin. Oncol., July 14, 2000; 18(14): 2676 - 2684. [Abstract] [Full Text] [PDF]

				J. Verweij, S. M. Lee, W. Ruka, J. Buesa, R. Coleman, R. van Hoessel, C. Seynaeve, E. D. di Paola, M. van Glabbeke, D. Tonelli, et al. 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 J. Clin. Oncol., May 10, 2000; 18(10): 2081 - 2086. [Abstract] [Full Text] [PDF]

				M. Van Glabbeke, A.T. van Oosterom, J.W. Oosterhuis, H. Mouridsen, D. Crowther, R. Somers, J. Verweij, A. Santoro, J. Buesa, and T. Tursz Prognostic Factors for the Outcome of Chemotherapy in Advanced Soft Tissue Sarcoma: An Analysis of 2,185 Patients Treated With Anthracycline-Containing First-Line Regimens—A European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study J. Clin. Oncol., January 1, 1999; 17(1): 150 - 150. [Abstract] [Full Text] [PDF]