Etoposide, Methotrexate, and Dactinomycin Alternating With Cyclophosphamide and Vincristine (EMACO) for Male Patients With HCG-expressing, Chemoresistant Germ Cell Tumors.

Abstract

OBJECTIVES:

To retrospectively analyze the efficacy and safety results of the combination of methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMACO) regimen for patients with human chorionic gonadotropin (HCG)-producing germ cell tumors and who had failed multiple courses of chemotherapy.

METHODS:

Patients who had failed at least 2 regimens received methotrexate 100 mg/m, followed by methotrexate 200 mg/m over 12 hours day 1, etoposide 100 mg/m and dactinomycin 0.5 mg days 1 and 2, folinic acid 25 mg orally every 6 hours days 2 and 3, alternating with cyclophosphamide 600 mg/m plus vincristine 1 mg/m day 8, every 21 days. Treatment was continued until marker normalization and for additional 2 cycles. Response rate, progression-free (PFS), and overall survival (OS) were the efficacy endpoints. Cox regression analyses examined the prognostic impact of candidate factors on PFS and OS.

RESULTS:

From February 92 to May 13, 41 patients were treated in third line (n=20, 49%) or beyond (n=21, 51%). Seventeen (41%) had received high-dose chemotherapy. Thirty-one patients (75.6%) had a response with marker reduction, including 4 complete (9.8%) and 5 (12.2%) partial responses with HCG normalization. Median PFS was 3 months (95% confidence interval [CI], 2-4) and median OS was 8 months (95% CI, 6-10). Most frequent grade 3-4 toxicity was hematologic (20 patients, 48.8%). One toxic death (cerebral hemorrhage) occurred. On multivariable analysis, the line of treatment (greater than third vs. third) was the only significant predictor of both PFS (hazard ratio: 2.50, 95% CI, 1.20-5.24, P=0.015) and OS (hazard ratio: 3.17, 95% CI: 1.46-6.89, P=0.004).

CONCLUSIONS:

EMACO is an attractive regimen with acceptable toxicity and could be considered an option for HCG-expressing germ cell tumors whenever multiple relapses occur.

• Authors: Daniele Raggi, Patrizia Giannatempo, Rosalba Miceli, Elena Farè, Luigi Piva, Davide Biasoni, Mario Catanzaro, Tullio Torelli, Silvia Stagni, Manuela Marongiu, Alessandro M Gianni, Nicola Nicolai, Roberto Salvioni, Andrea Necchi
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 40 Issue 1 Pg. 60-65 (02 2017) ISSN: 1537-453X [Electronic] United States
• PMID: 25089532 (Publication Type: Journal Article)

Chemical References

• Chorionic Gonadotropin
• Dactinomycin
• Vincristine
• Etoposide
• Cyclophosphamide
• Methotrexate

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chorionic Gonadotropin (biosynthesis)
• Cyclophosphamide (therapeutic use)
• Dactinomycin (therapeutic use)
• Drug Resistance, Neoplasm
• Etoposide (therapeutic use)
• Humans
• Male
• Methotrexate (therapeutic use)
• Neoplasms, Germ Cell and Embryonal (drug therapy, metabolism)
• Retrospective Studies
• Testicular Neoplasms (drug therapy, metabolism)
• Vincristine (therapeutic use)