etoposide IV

P1, N=55, Active, not recruiting, Boehringer Ingelheim | Recruiting --> Active, not recruiting

P3, N=330, Active, not recruiting, Radiation Therapy Oncology Group | Trial completion date: Jan 2025 --> Nov 2028 | Trial primary completion date: Jan 2025 --> Nov 2028 | Completed --> Active, not recruiting

P1, N=52, Active, not recruiting, City of Hope Medical Center | Suspended --> Active, not recruiting

We report the case of a 26-year-old man with a primary mediastinal yolk sac tumor who progressed despite multimodal therapy, including etoposide, ifosfamide, and cisplatin chemotherapy, high-dose carboplatin and etoposide with autologous stem cell transplantation, gemcitabine and paclitaxel, surgical debulking, and radiation therapy. No further disease-directed therapies were available, and he ultimately died from progressive metastatic disease. This case highlights the aggressive biology of platinum-resistant primary mediastinal yolk sac tumors, illustrates primary resistance to programmed death-1 inhibition, and underscores the urgent need for more effective salvage strategies in this high-risk population.

The resulting splice site gene-edited clone, designated MX2/SS-Edit, expressed reduced TOP2α/160 mRNA/protein, increased TOP2α/170 mRNA/protein, and exhibited partial restoration of sensitivity to mitoxantrone, etoposide, and amsacrine. SIGNIFICANCE STATEMENT: Results presented here validated drug resistance in the HL-60/MX2 leukemia cell line driven by intronic polyadenylation (IPA) within intron 33 of the DNA topoisomerase IIα (TOP2α) gene, which produced a truncated and predominantly cytoplasmic TOP2α protein isoform (TOP2α/160). Using CRISPR/Cas9/homology-directed repair gene editing, the weak exon 33/intron 33 5' splice site was enhanced to suppress IPA, which restored expression of full-length protein (TOP2α/170) and led to a gain-of-function in drug sensitivity, offering a potential strategy to overcome drug resistance.

Second, a network meta-analysis ranked the efficacy and safety of regimens including rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP); dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R); R-CHOP plus lenalidomide (R2-CHOP); R-CHOP plus ibrutinib (I+R-CHOP); R-CHOP plus zanubrutinib (Z+R-CHOP); and R-CHOP plus venetoclax (Ven-R-CHOP). DEL is a distinct high-risk subtype with quantifiable prognostic detriment. Z+R-CHOP emerges as a promising strategy requiring validation in prospective studies.

Mass spectrometry revealed minimal proteomic changes in iPSCs and moderate changes in NPCs, mainly involving mitotic regulators. In summary, no significant activation of canonical autophagy was detectable in iPSCs and NPCs within the tested time frame and under low-dose genotoxic conditions, although both cell types retain a functional autophagic machinery.

Interim PET/CT revealed in-field thoracic regression but widespread systemic progression; cisplatin-etoposide was added during the remaining RT course, followed by multisite palliative RT and consolidation cisplatin-etoposide-ifosfamide chemotherapy. This case suggests that staged, dose-escalated adaptive thoracic RT is feasible in selected patients with disseminated PPNC and compromised pulmonary function, providing durable in-field control and meaningful symptom palliation as part of a multimodal treatment approach. Molecular confirmation by NGS is essential for non-BRD4 fusions, and systemic therapy should be incorporated as early as safely feasible to address the high risk of distant dissemination.

This case highlights the diagnostic challenge of primary gastrointestinal ENKL in patients presenting with abdominal pain and hematochezia in the absence of computed tomography (CT) abnormalities. Persistent unexplained abdominal pain should prompt consideration of rare ulcerative small bowel diseases, including ENKL, particularly when perforation is a potential complication. Early multidisciplinary intervention is essential to improve the outcomes of this devastating condition.

Although combination chemotherapy remains essential for high-risk GTN, exposure to high cumulative doses of etoposide confers a risk of secondary t-MNs. Long-term hematologic surveillance and less leukemogenic strategies are warranted.

P3, N=550, Not yet recruiting, SystImmune Inc.

P3, N=395, Completed, Children's Oncology Group | Trial completion date: Nov 2026 --> Mar 2026 | Active, not recruiting --> Completed