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

Raggi, Daniele MD; Giannatempo, Patrizia MD; Miceli, Rosalba MD; Farè, Elena MD; Piva, Luigi MD; Biasoni, Davide MD; Catanzaro, Mario MD; Torelli, Tullio MD; Stagni, Silvia MD; Marongiu, Manuela MD; Gianni, Alessandro M. MD; Nicolai, Nicola MD; Salvioni, Roberto MD; Necchi, Andrea MD

American Journal of Clinical Oncology: February 2017 - Volume 40 - Issue 1 - p 60–65
doi: 10.1097/COC.0000000000000113
Original Articles: Genitourinary

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/m2, followed by methotrexate 200 mg/m2 over 12 hours day 1, etoposide 100 mg/m2 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/m2 plus vincristine 1 mg/m2 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.

Supplemental Digital Content is available in the text.

*Department of Medical Oncology

Clinical Epidemiology and Trials Organization Unit

Department of Surgery, Urology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori

§Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

The authors declare no conflicts of interest.

Reprints: Andrea Necchi, MD, Department of Medical Oncology, Medical Oncology 2 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, 20133 Milano, Italy. E-mail:

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