How effective is dose-intensive/myeloablative therapy against Ewing's sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review Journal Article
| Authors: | Kushner, B. H.; Meyers, P. A. |
| Article Title: | How effective is dose-intensive/myeloablative therapy against Ewing's sarcoma/primitive neuroectodermal tumor metastatic to bone or bone marrow? The Memorial Sloan-Kettering experience and a literature review |
| Abstract: | Purpose: Attempts to improve outcomes of patients with Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) metastatic to bone/bone morrow (BM) have focused on chemotherapy dose intensification strategies. We now present results achieved with that approach, as carried out at Memorial Sloan-Kettering Cancer Center (MSKCC) and as reported in the literature. Patients and Methods: Twenty-one unselected MSKCC patients with newly diagnosed ES/PNET metastatic to bone/BM received the ″P6″ protocol which includes cycles of cyclophosphamide (4.2 g/m2)/doxorubicin (75 mg/m2)/vincristine and cycles of isofamide (9 g/m2)/etoposide (500 mg/m2). Patients in complete/very good partial remission (CR/VGPR) after P6 received myeloablative therapy with either total-body irradiation (TBI) (hyperfractionated 15 Gy)/melphalan (180 mg/m2) or thiotepa (900 mg/m2)/carboplatin (1,500 mg/m2). We reviewed the literature. Results: Only one MSKCC patient became a long-term event-free survivor; all but one relapse was in a distant site. Initial responses to P6 were CR/VGPR in 19 patients, but eight of them plus two others developed PD while receiving or shortly after completing P6. Eight patients were treated with TBI/melphalan: four relapsed 2 to 7 months after transplantation; two died early of toxicity; one died of pulmonary failure 17 months after transplantation (no evidence of ES/PNET); and one remains in CR at more than 7 years. The three patients treated with thiotepa/carboplatin relapsed 3 to 4 months after transplantation. All reports on large series of unselected patients with ES/PNET metastatic to bone/BM showed similarly unsatisfactory results. Poor outcome was seen with use of active agents for ES/PNET-cyclophosphamide, ifosfamide, doxorubicin, dactinomycin, vincristine, etoposide - at standard dosages for prolonged periods of time and at higher dosages in intensive regimens for short or prolonged periods of time. No improvements in event-free survival rates occurred with successive cooperative group or large single-institutional studies that used increasingly aggressive chemotherapeutic approaches. Inclusion of ifosfamide with or without etoposide made no difference nor did consolidation of remission with myeloablative chemoradiotherapy. Secondary leukemia emerged as a major risk with dose-intensive regimens. Conclusion: The MSKCC experience and findings reported in the literature suggest that dose-intensive use of the chemotherapy agents with established activity against ES/PNET is reaching its efficacy and toxicity limits. A major impact on prognosis awaits the development of entirely novel therapies. © 2001 by American Society of Clinical Oncology. |
| Keywords: | adolescent; adult; cancer survival; child; clinical article; school child; bone neoplasms; review; cancer recurrence; doxorubicin; dose response; drug efficacy; bone metastasis; combined modality therapy; brain neoplasms; carboplatin; etoposide; antineoplastic combined chemotherapy protocols; cyclophosphamide; melphalan; vincristine; ifosfamide; thiotepa; ewing sarcoma; whole body radiation; bone marrow transplantation; sarcoma, ewing's; neuroectoderm tumor; drug induced disease; whole-body irradiation; neuroectodermal tumors, primitive; bone marrow neoplasms; bone marrow metastasis; humans; human; male; female; priority journal |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 19 |
| Issue: | 3 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2001-02-01 |
| Start Page: | 870 |
| End Page: | 880 |
| Language: | English |
| PUBMED: | 11157041 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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