Early experience with chemotherapy intensification for poor prognosis metastatic germ cell cancer and unfavorable tumor marker decline

Abstract

Introduction: Intensified chemotherapy improved outcomes for men with poor prognosis metastatic germ cell cancer (GCC) and unfavorable tumor marker decline (UTMD) after one cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy in the GETUG-13 trial. Herein, we report our experience to date using a similar approach.
 Methods: Patients were identified from our electronic GCC database. Men with poor prognosis GCC and UTMD were offered intensified chemotherapy consisting of T-BEP (three cycles) plus paclitaxel, ifosfamide, and cisplatin (TIP) (one cycle), along with prophylactic granulocyte-colony stimulating factor (G-CSF) and resection of residual masses. Cisplatin, etoposide and ifosfamide (PEI) replaced last cycle of T-BEP for bleomycin pulmonary concerns. Serious toxicities, progression-free survival, and overall survival were evaluated retrospectively.
 Results: Ten patients with poor prognosis GCC were identified May 2012 to April 2016. Eight patients had UTMD. Six were offered and received intensified chemotherapy (two T-BEPx3 + TIP and four T-BEPx2 + PEI + TIP). Serious toxicities included neutropenic sepsis, deep venous thrombosis, and C. difficile colitis, but there were no toxic deaths. One patient died of synchronous metastatic adenocarcinoma ex teratoma. The remaining five patients achieved marker negative partial response, two had residual mature teratoma excised, and four have no evidence of disease after surgery. All are alive at a median of 57.6 months (range 37.2‒65.3 months); one patient has grade 2 peripheral sensory neuropathy, and one patient has grade 2 cognitive disturbance. Of four patients treated with standard BEP, two have died of disease and two are alive at 44.9 and 47.2 months.
 Conclusions: Our experience with intensified chemotherapy for men with poor prognosis GCC and UTMD confirms that it is feasible, reasonably safe, and appears to provide results similar to those reported in GETUG-13.

Factors Determining Survival of Patients with Germ Cell Tumor (Single Institutional Experience)

“…Among germ cell tumours, the rate of decline in tumour markers reflects the response to therapy and chemo-sensitivity of disease. 14,15 We have observed a survival rate of 28% only in patients who failed to demonstrate a fall in markers after the first chemotherapy cycle. After primary therapy for advanced germ cell tumours, the residual disease is predictive and prognostically significant.…”