Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors.

Abstract

PURPOSE:

High cumulative epipodophyllotoxin dosages are reported to be associated with an elevated risk for secondary acute myeloid leukemia (s-AML). This study examined the risk of s-AML following cumulative etoposide doses greater than 2 g/m2 in patients with metastatic germ cell tumors (GCT).

PATIENTS AND METHODS:

The incidence of s-AML was retrospectively assessed in patients treated within clinical trials between January 1986 and February 1996 at four university centers. All patients received high-dose chemotherapy (HDCT) plus autologous stem-cell support for metastatic GCT, including high cumulative etoposide doses (> 2 g/m2). Minimum patient follow-up was 12 months. Standardized morbidity ratio (SMR) was calculated to estimate the risk associated with high cumulative etoposide doses, as compared with the general population.

RESULTS:

A total of 302 patients with a median age of 29 years (range, 15 to 55) received a median cumulative etoposide dose of 5 g/m2 (range, 2.4 to 14 g/m2). Four cases of s-AML were observed, which resulted in a cumulative incidence of 1.3% (95% confidence interval [CI], 0.38% to 3.59%) at 52 months of median follow-up (range, 12 to 198). Two cases of secondary myelodysplasia (s-MDS) developed in patients with primary mediastinal GCT. Based on the observed four cases of AML, which are most likely etoposide-related, the risk for developing s-AML (SMR, 160 [95% CI, 43.7 to 411.2]) is significantly increased in comparison to the age-matched general population.

CONCLUSION:

Due to the low incidence of AML in the general population, the significantly elevated risk for developing s-AML affects only 1.3% of all patients who receive etoposide doses greater than 2 g/m2. HDCT, including etoposide doses greater than 2 g/m2, is associated with an acceptably low incidence of s-AML in patients with advanced GCT.

• Authors: C Kollmannsberger, J Beyer, J P Droz, A Harstrick, J T Hartmann, P Biron, A Fléchon, P Schöffski, M Kuczyk, H J Schmoll, L Kanz, C Bokemeyer
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 16 Issue 10 Pg. 3386-91 (Oct 1998) ISSN: 0732-183X [Print] United States
• PMID: 9779717 (Publication Type: Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents, Phytogenic
• Etoposide

Topics

• Acute Disease
• Adolescent
• Adult
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects)
• Drug Administration Schedule
• Etoposide (administration & dosage, adverse effects)
• Germinoma (drug therapy, secondary)
• Hematopoietic Stem Cell Transplantation
• Humans
• Leukemia, Monocytic, Acute (chemically induced)
• Leukemia, Myeloid (chemically induced)
• Leukemia, Myelomonocytic, Acute (chemically induced)
• Male
• Mediastinal Neoplasms (drug therapy)
• Middle Aged
• Myelodysplastic Syndromes (chemically induced)
• Neoplasms, Second Primary (chemically induced)
• Retroperitoneal Neoplasms (drug therapy)
• Retrospective Studies
• Testicular Neoplasms (drug therapy)