POMB-ACE therapy for patients with international germ cell cancer collaborative group (IGCCCG) poor risk germ cell tumors (GCT): The USC experience

Abstract

4591 Background: Patients with poor-risk GCT have low rates of cure with standard therapy, with 3 year overall survival (OS) reported at 50% (IGCCCG, JCO 1997). POMB-ACE is a rapidly alternating, dose dense chemotherapy regimen developed to improve outcomes in this population, with reported 3 year OS of 75% (Bower et al, Ann Oncol 1997). We report our experience with this regimen, including analysis of acute and long-term toxicity. Methods: Subjects with poor-risk GCT, defined by IGCCCG criteria as AFP >10,000, bHCG >50,000, LDH > 10 × ULN, non-testicular primary, or non-pulmonary visceral metastases, who were diagnosed at Los Angeles County General Hospital and USC/Norris Cancer Center between 1998 and 2005 were identified using pathology and admission records. All clinical notes and laboratory data were reviewed. Results: Of 23 poor-risk GCT patients identified, 21 received POMB-ACE; 16 were treated at the county facility. 15 patients were Hispanic. 5 had primary mediastinal tumors. 16 were stage IIIC, 4 stage IIIB, and 1 stage IIIA. The median number of cycles was 8 (range 4–12), with a median interval between treatment cycles of 14 days (range 10–39). There were no treatment-related deaths. Febrile neutropenia occurred in 5.9% of treatment cycles, grade 3/4 hematologic toxicity in 19%, and other Grade 3/4 non-hematologic toxicities in 9.8%. G-CSF support was used with 24% of cycles. Nineteen patients (90%) had a partial response, of whom 8 underwent surgery for residual disease; only 1 had residual active tumor, 4 teratoma. Marker-negative status was achieved in 5 patients (23.8%). With median follow-up of 28 months, 9 subjects have recurred (43%) and 4 have died of disease progression. The estimated 2 year disease-free survival is 54%, and 3 year OS 75%. At the end of treatment, residual neuropathy persisted in 2 patients (9.5%), renal compromise in 2 (9.5%), pulmonary toxicity in 3 (14%), and otoxicity in 1 patient (4.7%). Conclusions: In our modern North American experience, POMB-ACE is feasible to administer, even in an uninsured population. This is an effective option in poor-risk GCT patients, with 3 year OS exceeding that achieved with standard therapy. Acute toxicity is modest, however persistent adverse sequelae are common. No significant financial relationships to disclose.