Journal of Clinical Oncology, Vol 11, 1276-1285, Copyright © 1993 by American Society of Clinical Oncology

ARTICLES

An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas

K Antman, J Crowley, SP Balcerzak, SE Rivkin, GR Weiss, A Elias, RB Natale, RM Cooper, B Barlogie and DL Trump
Dana-Farber Cancer Institute, Boston, MA.

PURPOSE AND METHODS: Doxorubicin alone or with dacarbazine (DTIC; AD) is considered the best available therapy for metastatic adult sarcomas. Ifosfamide is active in sarcomas that have failed to respond to a doxorubicin-based regimen. This study was designed to determine if ifosfamide added to doxorubicin and DTIC (ADI) significantly effects toxicity, response rate, and survival. Patients with measurable metastatic or unresectable sarcoma were randomized to receive AD or ADI. Patients with chondrosarcomas, fibrosarcomas, and other sarcomas of bone were eligible, although those with osteosarcoma, rhabdomyosarcoma, Ewing's sarcoma, Kaposi's sarcoma, and mesothelioma were excluded, as were patients with prior chemotherapy for sarcoma or prior doxorubicin. RESULTS: Between 1987 and 1989, 340 eligible patients were randomized. Significantly more myelosuppression, a higher response rate (17% v 32%; P < .002) and longer time to progression (4 v 6 months; P < .02) were observed for patients who received ifosfamide. An overall survival advantage for the two-drug regimen (12 v 13 months; P = .04) was not significant by multivariate analysis. CONCLUSION: In all three randomized trials of doxorubicin with and without ifosfamide (Eastern Cooperative Oncology Group [ECOG], European Organization for Research and Treatment of Cancer [EORTC], and this study), the response rate was higher for the ifosfamide-containing arm, significantly so in this and the ECOG studies. An improved response rate may be particularly important for the preoperative management of high-grade, borderline resectable lesions or pulmonary metastases, particularly in younger patients. In older patients, or for low-to intermediate-grade lesions, doxorubicin and DTIC followed by ifosfamide on progression is preferred.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. G. Casali, L. Jost, S. Sleijfer, J. Verweij, J.-Y. Blay, and On behalf of the ESMO Guidelines Working Group Soft tissue sarcomas: ESMO Clinical Recommendations for diagnosis, treatment and follow-up Ann. Onc., May 1, 2009; 20(suppl_4): iv132 - iv136. [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]

				P. Lorigan, J. Verweij, Z. Papai, S. Rodenhuis, A. Le Cesne, M. G. Leahy, J. A. Radford, M. M. Van Glabbeke, A. Kirkpatrick, P. C.W. Hogendoorn, et al. Phase III Trial of Two Investigational Schedules of Ifosfamide Compared With Standard-Dose Doxorubicin in Advanced or Metastatic Soft Tissue Sarcoma: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study J. Clin. Oncol., July 20, 2007; 25(21): 3144 - 3150. [Abstract] [Full Text] [PDF]

				R. G. Maki, J. K. Wathen, S. R. Patel, D. A. Priebat, S. H. Okuno, B. Samuels, M. Fanucchi, D. C. Harmon, S. M. Schuetze, D. Reinke, et al. Randomized Phase II Study of Gemcitabine and Docetaxel Compared With Gemcitabine Alone in Patients With Metastatic Soft Tissue Sarcomas: Results of Sarcoma Alliance for Research Through Collaboration Study 002 J. Clin. Oncol., July 1, 2007; 25(19): 2755 - 2763. [Abstract] [Full Text] [PDF]

				J. M. Taylor, T. M Braun, and Z. Li Comparing an experimental agent to a standard agent: relative merits of a one-arm or randomized two-arm Phase II design Clinical Trials, August 1, 2006; 3(4): 335 - 348. [Abstract] [PDF]

				T. J. Smith, J. Khatcheressian, G. H. Lyman, H. Ozer, J. O. Armitage, L. Balducci, C. L. Bennett, S. B. Cantor, J. Crawford, S. J. Cross, et al. 2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline J. Clin. Oncol., July 1, 2006; 24(19): 3187 - 3205. [Abstract] [Full Text] [PDF]

				S. Neragi-Miandoab Multimodality approach in management of malignant pleural mesothelioma Eur. J. Cardiothorac. Surg., January 1, 2006; 29(1): 14 - 19. [Abstract] [Full Text] [PDF]

				S. Sleijfer, C. Seynaeve, and J. Verweij Using Single-Agent Therapy in Adult Patients with Advanced Soft Tissue Sarcoma Can Still Be Considered Standard Care Oncologist, November 1, 2005; 10(10): 833 - 841. [Abstract] [Full Text] [PDF]

				J. D. Floyd, D. T. Nguyen, R. L. Lobins, Q. Bashir, D. C. Doll, and M. C. Perry Cardiotoxicity of Cancer Therapy J. Clin. Oncol., October 20, 2005; 23(30): 7685 - 7696. [Abstract] [Full Text] [PDF]

				D. R. D'Adamo, S. E. Anderson, K. Albritton, J. Yamada, E. Riedel, K. Scheu, G. K. Schwartz, H. Chen, and R. G. Maki Phase II Study of Doxorubicin and Bevacizumab for Patients With Metastatic Soft-Tissue Sarcomas J. Clin. Oncol., October 1, 2005; 23(28): 7135 - 7142. [Abstract] [Full Text] [PDF]

				J. Verweij Ecteinascidin-743 (ET-743): Early Test or Effective Treatment in Soft Tissue Sarcomas? J. Clin. Oncol., August 20, 2005; 23(24): 5420 - 5423. [Full Text] [PDF]

				R. Garcia-Carbonero, J.G. Supko, R.G. Maki, J. Manola, D.P. Ryan, D. Harmon, T.A. Puchalski, G. Goss, M.V. Seiden, A. Waxman, et al. Ecteinascidin-743 (ET-743) for Chemotherapy-Naive Patients With Advanced Soft Tissue Sarcomas: Multicenter Phase II and Pharmacokinetic Study J. Clin. Oncol., August 20, 2005; 23(24): 5484 - 5492. [Abstract] [Full Text] [PDF]

				A. S. Pappo, M. Devidas, J. Jenkins, B. Rao, R. Marcus, P. Thomas, M. Gebhardt, C. Pratt, and H. E. Grier Phase II Trial of Neoadjuvant Vincristine, Ifosfamide, and Doxorubicin With Granulocyte Colony-Stimulating Factor Support in Children and Adolescents With Advanced-Stage Nonrhabdomyosarcomatous Soft Tissue Sarcomas: A Pediatric Oncology Group Study J. Clin. Oncol., June 20, 2005; 23(18): 4031 - 4038. [Abstract] [Full Text] [PDF]

				A. Ferrari, M. Casanova, P. Collini, C. Meazza, R. Luksch, M. Massimino, G. Cefalo, M. Terenziani, F. Spreafico, S. Catania, et al. Adult-Type Soft Tissue Sarcomas in Pediatric-Age Patients: Experience at the Istituto Nazionale Tumori in Milan J. Clin. Oncol., June 20, 2005; 23(18): 4021 - 4030. [Abstract] [Full Text] [PDF]

				L. H. Baker Medical and Pediatric Oncology, Not Adult and Pediatric Oncology J. Clin. Oncol., June 20, 2005; 23(18): 4003 - 4005. [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]

				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]

				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]

				D. P. Ryan, T. Puchalski, J. G. Supko, D. Harmon, R. Maki, R. Garcia-Carbonero, C. Kuhlman, J. Winkelman, P. Merriam, T. Quigley, et al. A Phase II and Pharmacokinetic Study of Ecteinascidin 743 in Patients with Gastrointestinal Stromal Tumors Oncologist, December 1, 2002; 7(6): 531 - 538. [Abstract] [Full Text] [PDF]

				S. L. Spunt, D. A. Hill, A. M. Motosue, C. A. Billups, A. M. Cain, B. N. Rao, C. B. Pratt, T. E. Merchant, and A. S. Pappo Clinical Features and Outcome of Initially Unresected Nonmetastatic Pediatric Nonrhabdomyosarcoma Soft Tissue Sarcoma J. Clin. Oncol., August 1, 2002; 20(15): 3225 - 3235. [Abstract] [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]

				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]

				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]

				H. Ozer, J. O. Armitage, C. L. Bennett, J. Crawford, G. D. Demetri, P. A. Pizzo, C. A. Schiffer, T. J. Smith, G. Somlo, J. C. Wade, et al. 2000 Update of Recommendations for the Use of Hematopoietic Colony-Stimulating Factors: Evidence-Based, Clinical Practice Guidelines J. Clin. Oncol., October 20, 2000; 18(20): 3558 - 3585. [Full Text] [PDF]