Substitution of ifosfamide for cyclophosphamide in the TI-CE regimen: pharmacology and dose justification in a patient with refractory metastatic germ-cell tumor post-nephrectomy—A case report

Background: High-dose chemotherapy (HDCT) combined with autologous stem cell transplantation (ASCT) rescue is an effective treatment option for relapsed or refractory germ-cell tumors. The TI-CE regimen, consisting of paclitaxel and ifosfamide for stem cell mobilization followed by high dose carboplatin and etoposide with ASCT rescue, is frequently used in the treatment of refractory disease. This regimen is challenging in patients who have undergone unilateral nephrectomy, since potential nephrotoxicity of ifosfamide poses a serious risk for permanent damage of the preserved kidney. Currently, the literature lacks data on the substitution of ifosfamide in the TI-CE regimen for an alternative chemotherapeutic agent with equivalent potency while being less nephrotoxic. Case presentation: We present a case of a patient with refractory progressive metastatic germ-cell tumor who underwent nephrectomy and was successfully treated with a modified chemo-mobilization strategy. In the TI-CE protocol, ifosfamide was replaced for cyclophosphamide (TC-CE), resulting in a sufficient stem cell harvest through a single apheresis session. Post chemo-mobilization, LDH and hCG + hCGβ levels were normalized. Renal function remained stable throughout the course of treatment. Two months after HDCT, the patient showed a complete metabolic response, with no detectable tumor remnants. Currently, one year post-therapy, there are no signs of disease recurrence. Conclusion: An effective and potentially less nephrotoxic chemo-mobilization regimen, using paclitaxel and cyclophosphamide (TC-CE), was administered to a patient with refractory metastatic germ-cell tumor who underwent HDCT followed by ASCT rescue after unilateral nephrectomy. Cyclophosphamide demonstrated to be a viable substitute for ifosfamide within the TI-CE regimen.