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

J Cancer Res Clin Oncol. 2018 Sep;144(9):1817-1823. doi: 10.1007/s00432-018-2695-4. Epub 2018 Jul 5.

Abstract

Purpose: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Choriocarcinoma, non-gestational; Extensive tumor burden; Induction chemotherapy; Nonseminomatous germ cell tumor; Poor risk; Testicular cancers; Ultra-high tumor markers.

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Cisplatin / administration & dosage
  • Etoposide / administration & dosage
  • Humans
  • Male
  • Neoplasms, Germ Cell and Embryonal / drug therapy*
  • Neoplasms, Germ Cell and Embryonal / metabolism*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Prognosis
  • Retrospective Studies
  • Testicular Neoplasms / drug therapy*
  • Testicular Neoplasms / metabolism*
  • Testicular Neoplasms / pathology
  • alpha-Fetoproteins / metabolism

Substances

  • Biomarkers, Tumor
  • alpha-Fetoproteins
  • Etoposide
  • Cisplatin

Supplementary concepts

  • Nonseminomatous germ cell tumor