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 Cytotoxic agents
Germ Cell Tumours
Therapy
Biological therapy
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.