title: Paclitaxel, Ifosfamide, and Cisplatin Efficacy for First-Line Treatment of Patients With Intermediate- or Poor-Risk Germ Cell Tumors.
abstract: Paclitaxel, ifosfamide, and cisplatin (TIP) achieved complete responses (CRs) in two thirds of patients with advanced germ cell tumors (GCTs) who relapsed after first-line chemotherapy with cisplatin and etoposide with or without bleomycin. We tested the efficacy of first-line TIP in patients with intermediate- or poor-risk disease.
  
  
  
  In this prospective, multicenter, single-arm phase II trial, previously untreated patients with International Germ Cell Cancer Collaborative Group poor-risk or modified intermediate-risk GCTs received four cycles of TIP (paclitaxel 240 mg/m(2) over 2 days, ifosfamide 6 g/m(2) over 5 days with mesna support, and cisplatin 100 mg/m(2) over 5 days) once every 3 weeks with granulocyte colony-stimulating factor support. The primary end point was the CR rate.
  
  
  
  Of the first 41 evaluable patients, 28 (68%) achieved a CR, meeting the primary efficacy end point. After additional accrual on an extension phase, total enrollment was 60 patients, including 40 (67%) with poor risk and 20 (33%) with intermediate risk. Thirty-eight (68%) of 56 evaluable patients achieved a CR and seven (13%) achieved partial responses with negative markers (PR-negative) for a favorable response rate of 80%. Five of seven achieving PR-negative status had seminoma and therefore did not undergo postchemotherapy resection of residual masses. Estimated 3-year progression-free survival and overall survival rates were 72% (poor risk, 63%; intermediate risk, 90%) and 91% (poor risk, 87%; intermediate risk, 100%), respectively. Grade 3 to 4 toxicities consisted primarily of reversible hematologic or electrolyte abnormalities, including neutropenic fever in 18%.
  
  
  
  TIP demonstrated efficacy as first-line therapy for intermediate- and poor-risk GCTs with an acceptable safety profile. Given higher rates of favorable response, progression-free survival, and overall survival compared with prior first-line studies, TIP warrants further study in this population.
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA. feldmand@mskcc.org.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Feldman
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: James
authors.initials: J
authors.lastname: Hu
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Tanya B
authors.initials: TB
authors.lastname: Dorff
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lim
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Woo
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Maryann
authors.initials: M
authors.lastname: Carousso
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Hughes
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Joel
authors.initials: J
authors.lastname: Sheinfeld
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Manjit
authors.initials: M
authors.lastname: Bains
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Siamak
authors.initials: S
authors.lastname: Daneshmand
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Charlene
authors.initials: C
authors.lastname: Ketchens
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Bajorin
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Bosl
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
authors.affiliation: Darren R. Feldman, Kristina Lim, Sujata Patil, Kaitlin M. Woo, Maryann Carousso, Amanda Hughes, Joel Sheinfeld, Manjit Bains, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Memorial Sloan Kettering Cancer Center; Darren R. Feldman, Dean F. Bajorin, George J. Bosl, and Robert J. Motzer, Weill Medical College of Cornell University, New York, NY; and James Hu, Tanya B. Dorff, Siamak Daneshmand, Charlene Ketchens, and David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies
chemical_list: D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide