Dose-reduced first cycle of chemotherapy for prevention of life-threatening acute complications in nonseminomatous germ cell tumor patients with ultra high tumor markers and/or poor performance status

Patients with metastatic nonseminomatous germ cell tumors (mNSGCT) and a high tumor burden or a poor performance status at initial diagnosis are at risk from potentially life-threatening early complications during or after the first chemotherapy cycle. The outcomes with dose-reduced first cycle of chemotherapy in this population of patients are not well established.

We performed a retrospective analysis of patients with mNSGCT and International Germ Cell Cancer Collaborative Group (IGCCCG) poor risk features. All patients received cisplatin and etoposide-based combinations as first-line treatment. Ultra high tumor marker levels were defined as α-fetoprotein ≥ 100,000 ng/ml or human chorionic gonadotropin ≥ 200,000 mIU/ml. Before 2005, the first treatment cycle was administered at a full dose in our center. After 2005, we used an abbreviated course of cisplatin and etoposide (EP) for the first cycle, followed by subsequent full-dose administration.

From 1987 to 2012, 265 patients with poor risk features according to IGCCCG received first-line chemotherapy. Among them, 63 out of 265 (24%) patients had ultra high tumor marker levels and/or ECOG performance status of 3-4. Dose reduction of the first chemotherapy cycle was associated with a significant decrease of life-threatening complications from 76 to 44% (p = 0.01), but not with the overall survival (HR 0.99, 95% CI 0.44-2.26).

Dose reduction of the first EP cycle by 40-60% in the subgroup of poor risk patients with ultra high tumor marker levels and/or ECOG performance status 3-4 is associated with significantly lowered acute complication rates but not with overall survival.

Journal of cancer research and clinical oncology. 2018 Jul 05 [Epub ahead of print]

Alexey Tryakin, Mikhail Fedyanin, Anatoly Bulanov, Shalva Kashia, Ildar Kurmukov, Vsevolod Matveev, Igor Fainstein, Olga Gordeeva, Tatjana Zakharova, Sergei Tjulandin

Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, 115478, Russia. ., Department of Clinical Pharmacology and Chemotherapy, N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, 115478, Russia., Intensive Care Unit, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia., Urology Department, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia., Radiosurgery Department, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia., Department of Chemotherapy and Combined Treatment of Malignant Tumors, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia., Pathology Department, N.N. Blokhin Russian Cancer Research Center, Moscow, Russia.

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