790O - Gemcitabine, oxaliplatin, and paclitaxel (GOT) on a 2-weekly schedule in patients (pts) with refractory germ cell carcinoma: a phase II study conduc...

Date 30 September 2012
Event ESMO Congress 2012
Session Genitourinary tumors, bladder and testicular cancer
Topics Anti-Cancer Agents & Biologic Therapy
Germ Cell Tumours
Presenter David Quinn
Authors T.B. Dorff1, O. Hamid2, D. Tsao-Wei3, J. Hu1, J. Pinski4, A. Schuckman5, S. Daneshmand5, S. Groshen3, D. Raghavan6, D.I. Quinn1
  • 1Usc Norris Comprehensive Cancer Center, University of Southern California, Keck School of Medicine, 90033 - Los Angeles/US
  • 2Neuro-oncology Clinic, The Angeles Clinic and Research Institute, Los Angeles/US
  • 3Biostatistics, USC Norris Comprehensive Cancer Center, 90033 - Los Angeles/US
  • 4Medicine, University of Southern California, Keck School of Medicine, 90033 - Los Angeles/US
  • 5Institute Of Urology, Keck School of Medicine, 90033 - Los Angeles/US
  • 6Carolinas Healthcare, Levine Cancer Institute, 28232 - Charlotte/US

Abstract

Background

Modern therapy for GCT has transformed the disease but challenges remain in managing primary poor risk and refractory cancer.

Methods

Phase II study: 30 men with GCT progression ≤4 wks of a standard regimen (12) or after salvage (14) or stem cell regimen (3). Growing teratoma syndrome pts excluded. PS < =2, Age > 16, PD by RECIST/marker criteria. Regimen: Paclitaxel 170mg/m2/3h; Gemcitabine 800mg/m2/80mins; Oxaliplatin 100mg/m2/90min, increased to 125mg/m2 in cycle 2 if no major toxicity. Mg2+ & Ca2+ infused before oxaliplatin. G-CSF was not given prophylactically. The regimen was designed to maximize oxaliplatin density with full dosing of pts with recovering marrow & dose escalation for pts with limited toxicity in cycle 1. Retreatment criteria: ANC ≥1000 or 700 with monocytosis, platelets >75K. Pts with marker normalization had 3 further cycles. Primary endpoint: Response; 2nd: OS, PFS, toxicity Patient characterisitcs: Med age 32y, Race: white 41%, Hispanic 48%, Asian 10%, KPS ≥ 90% 66%, Primary site: testis 27, mediastinal 2: Histology: Seminoma: 7% Chorio 10%, YST 7%, Emb 3%, teratocarcinoma 13%, Undifferentiated 5%, mixed NSGCT 55%. Prior surgery for primary: 20, met resection 13. Med prior chemotherapy lines: 2 (R 1–7). Med (range) pre-GOT LDH: 173 (109-4504), AFP 22 (1–363002), bHCG 2.4 (2–247040) Endpoints: Median cycles 6 (1–14). Best RECIST response: CR2, PR7, uPR2, SD 11, PD 5; RR 31% (95%CIs 17-50%). 5 pts (4PR, 1SD) who underwent definitive surgery after trial therapy were rendered NED. Med FU 28 mos (R 3-81). Med OS: 16.7 mos (95%CIs 11.9–30.7), med PFS 10.8 (95%CIs 3.0−27.5), 2yr OS prob: 0.42 + /−0.10. Marker responses: 29% normalized. 7pts (24%) remain alive & NED >= 1 year. No association between ethnicity and RRor OS.Toxicity: 1pt died: pneumonia, gr 3/4 neutropenia 17pts, febrile neutropenia 7pt, neuropathy gr1/2: 19 pts, gr3 4pts, gr4 1pt, GI toxicity gr2/3 12 pts.

Conclusion

GOT given 2-wkly for refractory GCT produced high rates of marker & RECIST response & rendered 5 patients resectable. The median OS of 16.7 mos compares favorably with 6–13.5 mos in other series (Oechsle K Eur Urol 60: 850, 2011). ClinicalTrials.gov Identifier: NCT00183820

Disclosure

All authors have declared no conflicts of interest.