Very-high-dose short-term chemotherapy for poor-risk peripheral primitive neuroectodermal tumors, including Ewing's sarcoma, in children and young adults Journal Article


Authors: Kushner, B. H.; Meyers, P. A.; Gerald, W. L.; Healey, J. H.; La Quaglia, M. P.; Boland, P.; Wollner, N.; Casper, E. S.; Aledo, A.; Heller, G.; Schwartz, G. K.; Bonilla, M. A.; Lindsley, K. L.; Merchant, T. E.; Rosenfield, N. S.; Abramson, S. J.; Cheung, N. K. V.
Article Title: Very-high-dose short-term chemotherapy for poor-risk peripheral primitive neuroectodermal tumors, including Ewing's sarcoma, in children and young adults
Abstract: Purpose: To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma), while testing the feasibility of intensive use in adolescents and young adults of high-dose cyclophosphamide, doxorubicin, and vincristine (HD-CAV). Patients and Methods: This report concerns previously untreated patients with newly diagnosed pPNET deemed poor-risk because of a tumor volume more than 100 cm3 or metastases to bone or bone marrow. The P6 protocol consists of seven courses of chemotherapy. Courses 1, 2, 3, and 6 include 6-hour infusions of cyclophosphamide on days 1 and 2 for a total of 4,200 mg/m2 per course (140 mg/kg per course for patients < 10 years old), plus 72-hour infusions of doxorubicin 75 mg/m2 and vincristine 2.0 mg/m2 beginning on day 1 (HD-CAV). Courses 4, 5, and 7 consist of 1-hour infusions of ifosfamide 1.8 g/m2/d and etoposide (VP-16) 100 mg/m2/d, for 5 days. Granulocyte colony-stimulating factor (G-CSF) and mesna are used. Courses start after neutrophil counts reach 500/μL and platelet counts reach 100,000/μL. Surgical resection follows course 3 and radiotherapy follows completion of all chemotherapy. Results: Among the first 36 consecutive assessable patients (median age, 17 years), HD-CAV achieved excellent histopathologic or clinical responses in 34 patients and partial responses (PRs) in two patients. For 24 patients with locoregional disease, the 2-year event-free survival rate was 77%; adverse events were two locoregional relapses, one distant relapse, and one secondary leukemia. All six patients with metastatic disease limited to lungs achieved a complete response (CR) and did not relapse; one is in remission 36+ months from diagnosis, but the other patients are not assessable in terms of long-term efficacy of the P6 protocol because of short follow-up time (n = 3), additional systemic therapy (bone marrow transplantation), or septic death (autopsy showed no residual pPNET). All six patients with widespread metastases had major responses, including eradication of extensive bone marrow involvement, but distant relapses ensued. Myelosuppression was severe, but most patients received the first three courses of HD-CAV within 6 to 7 weeks. Major nonhematologic toxicities were mucositis and peripheral neuropathy. Conclusion: Excellent antitumor efficacy and manageable toxicity support the dose-intensive use of HD-CAV for pPNET in children, as well as in young adults. Consolidation of remissions of pPNET metastatic to bone and bone marrow remains a therapeutic challenge.
Keywords: adolescent; adult; cancer chemotherapy; cancer survival; child; clinical article; school child; leukemia; cancer recurrence; doxorubicin; metastasis; bone marrow suppression; tumor volume; etoposide; cyclophosphamide; vincristine; ifosfamide; ewing sarcoma; thrombocyte count; sepsis; leukocyte count; mesna; bone marrow transplantation; granulocyte colony stimulating factor; neuroectoderm tumor; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 13
Issue: 11
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 1995-11-01
Start Page: 2796
End Page: 2804
Language: English
DOI: 10.1200/jco.1995.13.11.2796
PUBMED: 7595741
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Brian Kushner
    190 Kushner
  2. Glenn Heller
    295 Heller
  3. Nai-Kong Cheung
    439 Cheung
  4. Gary Schwartz
    358 Schwartz
  5. Patrick J Boland
    130 Boland
  6. Nancy S Rosen
    27 Rosen
  7. William L Gerald
    367 Gerald
  8. Paul Meyers
    244 Meyers
  9. John H Healey
    374 Healey
  10. Ephraim S Casper
    57 Casper