Phase Ii Trial Of Paclitaxel, Ifosfamide, And Cisplatin (Tip) For Previously Untreated Patients (Pts) With Intermediate- Or Poor-Risk Germ Cell Tumors (Gct)

336 Background: Durable progression-free survival (PFS) rates for pts with intermediate- and poor-risk GCT approximate only 75% and 50%, respectively with standard BEP chemotherapy. This phase II study investigated first-line TIP in this population.Pts age ≥18 with previously untreated poor-risk or modified intermediate-risk (LDH ≥3x upper limit of normal [ULN]) GCT were eligible. Four cycles of TIP were given every 21 days, consisting of paclitaxel 120mg/m(2) on days 1-2; ifosfamide 1200mg/m(2) (with mesna support) on days 1-5; and cisplatin 20mg/m(2)on days 1-5. Peg-filgrastim was given on day 6 and levofloxacin on days 7-13 for prevention of neutropenic fever. The primary endpoint was the complete response (CR) rate; secondary endpoints included PFS and toxicity. A Simon's two-stage design was used: if ≥11 CRs were observed in the first 18 pts, a total of 41 evaluable pts would be accrued with the trial considered positive if ≥27 CRs were achieved.Of 44 men (median age 27 [range 18-56]) enrolled; 38 had nonseminoma and 6 had seminoma; 29 were poor-risk and 15 intermediate-risk. Primary site was testis in 30, mediastinum in 11, retroperitoneum in 3. Most pts had lung (n=31) and abdomen/pelvis (n=29) metastasis, and 14, 6, and 1 had liver, bone, and brain metastasis, respectively. Markers were elevated in 42 pts. Forty pts received all 4 TIP cycles; 3 pts were withdrawn after 2 cycles for allergic reactions to paclitaxel and were inevaluable for response, and 1 pt completed only 3 cycles in order to undergo surgery for growing teratoma syndrome (evaluable). Of 41 evaluable pts, 29 (72%, 90% CI: 60% - 78%) achieved a CR and 5 (all seminoma) achieved a PR with negative markers (PR-); 7 pts had incomplete responses and 2 pts relapsed from PR- or CR. With a median follow-up of 2.1 years, estimated 1-year PFS was 79% (95% CI: 64% - 89%) and 3-year overall survival 97% (95% CI: 83% - 100%). There were no toxic deaths. Grade 3/4 toxicities were primarily hematologic but only 7 (16%) pts developed neutropenic fever.TIP demonstrated promising efficacy and was tolerable in intermediate- and poor-risk GCT pts. A randomized trial of TIP versus BEP is being planned.NCT00470366.