Testing the Use of the Usual Chemotherapy Before and After Surgery for Removable Pancreatic Cancer
Pancreatic Adenosquamous Carcinoma, Resectable Pancreatic Adenocarcinoma, Pancreatic Cancer
About this trial
This is an interventional treatment trial for Pancreatic Adenosquamous Carcinoma
Eligibility Criteria
Inclusion Criteria:
PRE-REGISTRATION:
- Pathology: Histologic or cytologic proof of pancreatic adenocarcinoma or adenosquamous carcinoma
- TNM Stage: Tx-4, N0-1, M0 (M0 disease does not include spread to distant lymph nodes and organs)
Resectable Primary Tumor: Local radiographic reading must be consistent with resectable disease defined as the following on 1) arterial and venous phase contrast-enhanced abdominal/pelvic CT scan or abdominal/pelvic magnetic resonance imaging (MRI) scan and 2) chest CT:
- No involvement or abutment of the celiac artery, common hepatic artery, superior mesenteric artery, or replaced right hepatic artery (if applicable)
- Less than 180 degree interface between tumor and vessel wall of the portal vein or superior mesenteric vein, and patent portal vein/splenic vein confluence
- No evidence of metastatic disease
- Measurable disease or non-measurable disease o Non-measurable disease is defined as cytologic or histologic confirmation of adenocarcinoma of adenosquamous carcinoma by fine needle aspiration or core-biopsy of the pancreas without measurable disease by radiographic imaging
REGISTRATION:
- Confirmation of resectable disease by real-time central imaging review by the Alliance Imaging Core Lab at Imaging and Radiation Oncology Core (IROC) Ohio
- Determined to be appropriate candidate for curative-intent pancreatectomy by surgeon intending to perform the resection
- No prior radiation therapy, chemotherapy, targeted therapy, investigational therapy, or surgery for pancreatic cancer
- Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.
- Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Total Neuropathy Score < 2
- Absolute neutrophil count (ANC) >= 1,500/uL
- Platelet count >= 100,000/uL
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (If obstructive jaundice is present, then biliary drainage must be initiated and total bilirubin =< 3.0)
- Creatinine =< 1.5 x ULN OR calculated (Calc.) creatinine clearance >= 30 mL/min (Calculated using the Cockcroft-Gault equation)
- No known Gilbert's Syndrome or known homozygosity for UGAT1A1*28 polymorphism
- No comorbid conditions that would prohibit curative-intent pancreatectomy
- Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug prior to registration
- Chronic concomitant treatment with strong inducers of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inducers must discontinue the drug prior to registration
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Thomas HospitalRecruiting
- Mobile Infirmary Medical CenterRecruiting
- University of South Alabama Mitchell Cancer InstituteRecruiting
- Anchorage Associates in Radiation Medicine
- Alaska Breast Care and Surgery LLC
- Alaska Oncology and Hematology LLC
- Alaska Women's Cancer Care
- Anchorage Oncology Centre
- Katmai Oncology Group
- Providence Alaska Medical Center
- Banner University Medical Center - TucsonRecruiting
- University of Arizona Cancer Center-North CampusRecruiting
- Mercy Hospital Fort Smith
- NEA Baptist Memorial Hospital and Fowler Family Cancer Center - JonesboroRecruiting
- University of Arkansas for Medical SciencesRecruiting
- Kaiser Permanente-Deer Valley Medical CenterRecruiting
- Sutter Cancer Centers Radiation Oncology Services-Auburn
- Alta Bates Summit Medical Center-Herrick CampusRecruiting
- Providence Saint Joseph Medical Center/Disney Family Cancer Center
- Mills-Peninsula Medical Center
- Sutter Cancer Centers Radiation Oncology Services-Cameron Park
- Community Cancer Institute
- Kaiser Permanente DublinRecruiting
- Kaiser Permanente-FremontRecruiting
- Kaiser Permanente-FresnoRecruiting
- UC San Diego Moores Cancer CenterRecruiting
- Los Angeles County-USC Medical CenterRecruiting
- USC / Norris Comprehensive Cancer CenterRecruiting
- Cedars Sinai Medical CenterRecruiting
- Memorial Medical Center
- Kaiser Permanente-ModestoRecruiting
- Palo Alto Medical Foundation-Camino Division
- Kaiser Permanente-OaklandRecruiting
- Saint Joseph Hospital - OrangeRecruiting
- Palo Alto Medical Foundation Health Care
- Stanford Cancer Institute Palo AltoRecruiting
- Kaiser Permanente-Redwood CityRecruiting
- Kaiser Permanente-RichmondRecruiting
- Kaiser Permanente-RosevilleRecruiting
- Sutter Cancer Centers Radiation Oncology Services-Roseville
- Sutter Roseville Medical Center
- Kaiser Permanente Downtown CommonsRecruiting
- Sutter Medical Center Sacramento
- University of California Davis Comprehensive Cancer Center
- Kaiser Permanente-South SacramentoRecruiting
- UC San Diego Medical Center - HillcrestRecruiting
- California Pacific Medical Center-Pacific CampusRecruiting
- Kaiser Permanente-San FranciscoRecruiting
- UCSF Medical Center-Mission BayRecruiting
- Kaiser Permanente-Santa Teresa-San JoseRecruiting
- Kaiser Permanente San LeandroRecruiting
- Mills Health CenterRecruiting
- Kaiser San Rafael-GallinasRecruiting
- Kaiser Permanente Medical Center - Santa ClaraRecruiting
- Kaiser Permanente-Santa RosaRecruiting
- Kaiser Permanente-South San FranciscoRecruiting
- Kaiser Permanente-StocktonRecruiting
- Palo Alto Medical Foundation-Sunnyvale
- Sutter Cancer Centers Radiation Oncology Services-Vacaville
- Kaiser Permanente Medical Center-VacavilleRecruiting
- Kaiser Permanente-VallejoRecruiting
- Sutter Solano Medical Center/Cancer Center
- Kaiser Permanente-Walnut CreekRecruiting
- Porter Adventist Hospital
- Danbury HospitalRecruiting
- Smilow Cancer Hospital-Derby Care CenterRecruiting
- Smilow Cancer Hospital Care Center-FairfieldRecruiting
- Smilow Cancer Hospital Care Center at GlastonburyRecruiting
- Smilow Cancer Hospital Care Center at GreenwichRecruiting
- Smilow Cancer Hospital Care Center - GuilfordRecruiting
- Yale UniversityRecruiting
- Yale-New Haven Hospital North Haven Medical CenterRecruiting
- Norwalk HospitalRecruiting
- Smilow Cancer Hospital-Orange Care CenterRecruiting
- Smilow Cancer Hospital-Torrington Care CenterRecruiting
- Smilow Cancer Hospital Care Center-TrumbullRecruiting
- Smilow Cancer Hospital-Waterbury Care CenterRecruiting
- Smilow Cancer Hospital Care Center - WaterfordRecruiting
- MedStar Georgetown University HospitalRecruiting
- Sibley Memorial HospitalRecruiting
- AdventHealth Altamonte
- Mount Sinai Comprehensive Cancer Center at Aventura
- UM Sylvester Comprehensive Cancer Center at Coral GablesRecruiting
- UM Sylvester Comprehensive Cancer Center at Deerfield BeachRecruiting
- Regional Cancer Center-Lee Memorial Health SystemRecruiting
- Lakeland Regional Health Hollis Cancer CenterRecruiting
- Mount Sinai Medical CenterRecruiting
- University of Miami Miller School of Medicine-Sylvester Cancer Center
- UM Sylvester Comprehensive Cancer Center at KendallRecruiting
- AdventHealth Orlando
- UM Sylvester Comprehensive Cancer Center at PlantationRecruiting
- Cleveland Clinic-WestonRecruiting
- Phoebe Putney Memorial HospitalRecruiting
- Augusta University Medical Center
- Queen's Medical CenterRecruiting
- Kaiser Permanente Moanalua Medical CenterRecruiting
- Saint Alphonsus Cancer Care Center-Boise
- Saint Luke's Cancer Institute - BoiseRecruiting
- Saint Alphonsus Cancer Care Center-Caldwell
- Kootenai Health - Coeur d'Alene
- Saint Luke's Cancer Institute - FruitlandRecruiting
- Idaho Urologic Institute-Meridian
- Saint Luke's Cancer Institute - MeridianRecruiting
- Saint Luke's Cancer Institute - NampaRecruiting
- Saint Alphonsus Cancer Care Center-Nampa
- Kootenai Clinic Cancer Services - Post Falls
- Saint Luke's Cancer Institute - Twin FallsRecruiting
- Rush - Copley Medical Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Memorial Hospital of Carbondale
- SIH Cancer Institute
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Northwestern UniversityRecruiting
- John H Stroger Jr Hospital of Cook CountyRecruiting
- University of IllinoisRecruiting
- University of Chicago Comprehensive Cancer Center
- Carle at The Riverfront
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial HospitalRecruiting
- Northwestern Medicine Cancer Center KishwaukeeRecruiting
- Carle Physician Group-Effingham
- Crossroads Cancer CenterRecruiting
- Illinois CancerCare-Eureka
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- Northwestern Medicine Cancer Center DelnorRecruiting
- Illinois CancerCare-Kewanee Clinic
- Illinois CancerCare-Macomb
- Carle Physician Group-Mattoon/Charleston
- Loyola University Medical CenterRecruiting
- Good Samaritan Regional Health Center
- Cancer Care Center of O'Fallon
- University of Chicago Medicine-Orland Park
- Illinois CancerCare-Ottawa Clinic
- Illinois CancerCare-Pekin
- Illinois CancerCare-PeoriaRecruiting
- Methodist Medical Center of IllinoisRecruiting
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Illinois CancerCare-Princeton
- Southern Illinois University School of MedicineRecruiting
- Springfield ClinicRecruiting
- Memorial Medical CenterRecruiting
- Carle Cancer Center
- The Carle Foundation Hospital
- Northwestern Medicine Cancer Center WarrenvilleRecruiting
- Memorial Hospital of South Bend
- Mary Greeley Medical Center
- McFarland Clinic - AmesRecruiting
- Iowa Methodist Medical Center
- Medical Oncology and Hematology Associates-Des MoinesRecruiting
- Broadlawns Medical Center
- Mercy Medical Center - Des MoinesRecruiting
- Iowa Lutheran Hospital
- University of Iowa/Holden Comprehensive Cancer Center
- Methodist West Hospital
- Baptist Health Lexington
- University of Kentucky/Markey Cancer CenterRecruiting
- The James Graham Brown Cancer Center at University of LouisvilleRecruiting
- Baptist Health Louisville
- Baptist Health Madisonville/Merle Mahr Cancer Center
- LSU Health Baton Rouge-North ClinicRecruiting
- Louisiana Hematology Oncology Associates LLCRecruiting
- Mary Bird Perkins Cancer CenterRecruiting
- Our Lady of the Lake Physicians Group - Medical OncologyRecruiting
- Medical Center of Baton RougeRecruiting
- Ochsner High GroveRecruiting
- Northshore Oncology Associates-CovingtonRecruiting
- Ochsner Hematology Oncology North Shore - Covington (West Region)Recruiting
- Terrebonne General Medical CenterRecruiting
- Ochsner Medical Center KennerRecruiting
- University Medical Center New OrleansRecruiting
- Ochsner Medical Center JeffersonRecruiting
- Greater Baltimore Medical CenterRecruiting
- UM Saint Joseph Medical Center
- Tufts Medical CenterRecruiting
- Massachusetts General Hospital Cancer Center
- Boston Medical CenterRecruiting
- Dana-Farber Cancer Institute
- Hickman Cancer Center
- Saint Joseph Mercy HospitalRecruiting
- University of Michigan Comprehensive Cancer CenterRecruiting
- Saint Joseph Mercy BrightonRecruiting
- Saint Joseph Mercy CantonRecruiting
- Saint Joseph Mercy ChelseaRecruiting
- Wayne State University/Karmanos Cancer InstituteRecruiting
- Henry Ford HospitalRecruiting
- Ascension Saint John HospitalRecruiting
- Weisberg Cancer Treatment CenterRecruiting
- Spectrum Health at Butterworth CampusRecruiting
- West Michigan Cancer CenterRecruiting
- Ascension Providence Hospitals - NoviRecruiting
- William Beaumont Hospital-Royal OakRecruiting
- Ascension Saint Mary's HospitalRecruiting
- Ascension Providence Hospitals - SouthfieldRecruiting
- William Beaumont Hospital - TroyRecruiting
- Saint John Macomb-Oakland HospitalRecruiting
- Baptist Cancer Center-GrenadaRecruiting
- Baptist Memorial Hospital and Cancer Center-Union CountyRecruiting
- Baptist Memorial Hospital and Cancer Center-OxfordRecruiting
- Baptist Memorial Hospital and Cancer Center-DesotoRecruiting
- Saint Louis Cancer and Breast Institute-Ballwin
- Saint Francis Medical Center
- Southeast Cancer Center
- MU Health - University Hospital/Ellis Fischel Cancer Center
- Capital Region Southwest Campus
- Mercy Hospital Joplin
- Saint Luke's Hospital of Kansas City
- Delbert Day Cancer Institute at PCRMC
- Mercy Clinic-Rolla-Cancer and Hematology
- Heartland Regional Medical Center
- Washington University School of Medicine
- Mercy Hospital South
- Missouri Baptist Medical CenterRecruiting
- Mercy Hospital Saint Louis
- Sainte Genevieve County Memorial Hospital
- Mercy Hospital Springfield
- CoxHealth South Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Billings Clinic Cancer Center
- Bozeman Deaconess Hospital
- Benefis Healthcare- Sletten Cancer Institute
- Great Falls Clinic
- Kalispell Regional Medical Center
- Community Medical Hospital
- Nebraska Methodist HospitalRecruiting
- OptumCare Cancer Care at CharlestonRecruiting
- Renown Regional Medical CenterRecruiting
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer CenterRecruiting
- Memorial Sloan Kettering Basking RidgeRecruiting
- Cooper Hospital University Medical CenterRecruiting
- Englewood Hospital and Medical CenterRecruiting
- Jersey City Medical CenterRecruiting
- Monmouth Medical Center Southern CampusRecruiting
- Saint Barnabas Medical CenterRecruiting
- Monmouth Medical CenterRecruiting
- Memorial Sloan Kettering MonmouthRecruiting
- Memorial Sloan Kettering BergenRecruiting
- Jersey Shore Medical CenterRecruiting
- Rutgers Cancer Institute of New JerseyRecruiting
- The Valley Hospital-Luckow PavilionRecruiting
- Valley HospitalRecruiting
- Holy Name HospitalRecruiting
- University of New Mexico Cancer CenterRecruiting
- Northwell Health Imbert Cancer CenterRecruiting
- Montefiore Medical Center-Einstein CampusRecruiting
- Montefiore Medical Center-Weiler HospitalRecruiting
- Montefiore Medical Center - Moses CampusRecruiting
- Memorial Sloan Kettering CommackRecruiting
- Cancer Institute at Saint Francis HospitalRecruiting
- Hematology Oncology Associates of Central New York-East Syracuse
- Northwell Health Cancer Institute at HuntingtonRecruiting
- Memorial Sloan Kettering WestchesterRecruiting
- Northwell Health/Center for Advanced MedicineRecruiting
- North Shore University HospitalRecruiting
- Long Island Jewish Medical CenterRecruiting
- Mount Sinai WestRecruiting
- Lenox Hill HospitalRecruiting
- Mount Sinai HospitalRecruiting
- Manhattan Eye Ear and Throat HospitalRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- Upstate Cancer Center at OneidaRecruiting
- Upstate Cancer Center at OswegoRecruiting
- University of RochesterRecruiting
- Staten Island University HospitalRecruiting
- Stony Brook University Medical Center
- State University of New York Upstate Medical UniversityRecruiting
- SUNY Upstate Medical Center-Community CampusRecruiting
- Memorial Sloan Kettering NassauRecruiting
- Wilmot Cancer Institute at WebsterRecruiting
- Dickstein Cancer Treatment CenterRecruiting
- Carolinas Medical Center/Levine Cancer InstituteRecruiting
- Duke University Medical CenterRecruiting
- East Carolina UniversityRecruiting
- Vidant Oncology-KinstonRecruiting
- Duke Women's Cancer Care RaleighRecruiting
- Duke Raleigh HospitalRecruiting
- Wake Forest University Health SciencesRecruiting
- Sanford Broadway Medical CenterRecruiting
- Sanford Roger Maris Cancer CenterRecruiting
- Cleveland Clinic Akron GeneralRecruiting
- Adena Regional Medical Center
- Case Western Reserve UniversityRecruiting
- MetroHealth Medical CenterRecruiting
- Cleveland Clinic Cancer Center/Fairview HospitalRecruiting
- Cleveland Clinic FoundationRecruiting
- Ohio State University Comprehensive Cancer Center
- Mount Carmel East HospitalRecruiting
- Riverside Methodist Hospital
- Grant Medical Center
- The Mark H Zangmeister CenterRecruiting
- Mount Carmel Health Center West
- Doctors Hospital
- Miami Valley HospitalRecruiting
- Dublin Methodist Hospital
- Mount Carmel Grove City HospitalRecruiting
- OhioHealth Mansfield Hospital
- Cleveland Clinic Cancer Center MansfieldRecruiting
- Marietta Memorial Hospital
- Hillcrest Hospital Cancer CenterRecruiting
- Licking Memorial Hospital
- Newark Radiation Oncology
- Southern Ohio Medical Center
- North Coast Cancer CareRecruiting
- University of ToledoRecruiting
- Toledo Clinic Cancer Centers-ToledoRecruiting
- Saint Ann's HospitalRecruiting
- Cleveland Clinic Wooster Family Health and Surgery CenterRecruiting
- Genesis Healthcare System Cancer Care Center
- University of Oklahoma Health Sciences CenterRecruiting
- Mercy Hospital Oklahoma City
- Saint Charles Health System
- Clackamas Radiation Oncology Center
- Providence Cancer Institute Clackamas Clinic
- Bay Area Hospital
- Providence Newberg Medical CenterRecruiting
- Providence Portland Medical CenterRecruiting
- Providence Saint Vincent Medical CenterRecruiting
- Kaiser Permanente Northwest
- Jefferson Abington Hospital
- Lehigh Valley Hospital-Cedar CrestRecruiting
- Ephrata Cancer CenterRecruiting
- Saint Vincent Hospital
- Adams Cancer CenterRecruiting
- Jefferson Hospital
- Sechler Family Cancer CenterRecruiting
- Forbes Hospital
- Thomas Jefferson University Hospital
- Allegheny General Hospital
- West Penn Hospital
- Reading HospitalRecruiting
- Wexford Health and Wellness Pavilion
- Asplundh Cancer PavilionRecruiting
- WellSpan Health-York Cancer CenterRecruiting
- WellSpan Health-York HospitalRecruiting
- Smilow Cancer Hospital Care Center - WesterlyRecruiting
- Ralph H Johnson VA Medical CenterRecruiting
- Medical University of South Carolina
- Prisma Health Cancer Institute - FarisRecruiting
- Prisma Health Cancer Institute - EastsideRecruiting
- Prisma Health Cancer Institute - GreerRecruiting
- Prisma Health Cancer Institute - SenecaRecruiting
- Sanford Cancer Center Oncology ClinicRecruiting
- Sanford USD Medical Center - Sioux FallsRecruiting
- Baptist Memorial Hospital and Cancer Center-ColliervilleRecruiting
- University of Tennessee - KnoxvilleRecruiting
- Baptist Memorial Hospital and Cancer Center-MemphisRecruiting
- The Don and Sybil Harrington Cancer CenterRecruiting
- UT Southwestern/Simmons Cancer Center-DallasRecruiting
- UT Southwestern/Simmons Cancer Center-Fort WorthRecruiting
- UT Southwestern Clinical Center at Richardson/PlanoRecruiting
- University of Texas Health Science Center at San AntonioRecruiting
- University of Vermont Medical Center
- Inova Schar Cancer InstituteRecruiting
- Inova Fairfax HospitalRecruiting
- Sentara Leigh HospitalRecruiting
- Sentara Norfolk General HospitalRecruiting
- Virginia Commonwealth University/Massey Cancer CenterRecruiting
- VCU Community Memorial Health CenterRecruiting
- Providence Regional Cancer System-Aberdeen
- Overlake Medical Center
- PeaceHealth Saint Joseph Medical Center
- Providence Regional Cancer System-Centralia
- Swedish Cancer Institute-Edmonds
- Providence Regional Cancer PartnershipRecruiting
- Swedish Cancer Institute-Issaquah
- Providence Regional Cancer System-Lacey
- PeaceHealth Saint John Medical Center
- Swedish Medical Center-Ballard Campus
- FHCC South Lake UnionRecruiting
- Swedish Medical Center-First Hill
- University of Washington Medical Center - MontlakeRecruiting
- PeaceHealth United General Medical Center
- PeaceHealth Southwest Medical Center
- Providence Saint Mary Regional Cancer Center
- West Virginia University Charleston DivisionRecruiting
- Langlade Hospital and Cancer Center
- Marshfield Medical Center-EC Cancer CenterRecruiting
- Gundersen Lutheran Medical CenterRecruiting
- Marshfield Medical Center-MarshfieldRecruiting
- Aspirus Medford Hospital
- Ascension Columbia Saint Mary's Hospital OzaukeeRecruiting
- Ascension Columbia Saint Mary's Hospital - MilwaukeeRecruiting
- Marshfield Clinic-Minocqua CenterRecruiting
- Marshfield Medical Center-Rice LakeRecruiting
- Marshfield Medical Center-River Region at Stevens PointRecruiting
- Aspirus Regional Cancer CenterRecruiting
- Marshfield Medical Center - WestonRecruiting
- Aspirus Cancer Care - Wisconsin Rapids
- Welch Cancer Center
- BCCA-Vancouver Cancer CentreRecruiting
- BCCA-Vancouver Island Cancer CentreRecruiting
- CancerCare ManitobaRecruiting
- QEII Health Sciences Centre/Nova Scotia Health AuthorityRecruiting
- Juravinski Cancer Centre at Hamilton Health SciencesRecruiting
- Ottawa Hospital and Cancer Center-General CampusRecruiting
- Odette Cancer Centre- Sunnybrook Health Sciences CentreRecruiting
- The Research Institute of the McGill University Health Centre (MUHC)Recruiting
- CHU de Quebec-L'Hotel-Dieu de Quebec (HDQ)Recruiting
- Centre Hospitalier Universitaire de Sherbrooke-FleurimontRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Arm I (perioperative chemotherapy, surgery)
Arm II (surgery, adjuvant chemotherapy)
Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Within 2-8 weeks of completing neoadjuvant chemotherapy, patients undergo surgical resection. Patients then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 4 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo surgical resection. Beginning 3-12 weeks after surgery, patients then receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and leucovorin calcium over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-3. Treatment repeats every 14 days for 12 cycles in the absence of disease progression or unacceptable toxicity.