Julian R Molina1, Nathan R Foster2, Thanyanan Reungwetwattana3, Garth D Nelson2, Andrew V Grainger4, Preston D Steen5, Philip J Stella6, Randolph Marks7, John Wright8, Alex A Adjei9. 1. Division of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. Electronic address: molina.julian@mayo.edu. 2. Division of Biomedical Statistics and Informatics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. 3. Division of Medical Oncology, Department of Internal Medicine, Ramathibodi Hospital, Bangkok, Thailand. 4. Columbus Oncology & Hematology, Inc., 810 Jasonway Avenue, Suite A, Columbus, OH 43214l, United States. 5. MeritCare Hospital CCOP, 820 4(th) Street North, Fargo, ND 58102, United States. 6. St. Joseph Mercy Cancer Center, 5301 McAuley Drive, Suite C-139, Ypsilanti, MI 48197, United States. 7. Division of Medical Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States. 8. CTEP Program, National Cancer Institute, Executive Plaza North, Suite 7115A, Rockville, MD 20852-7426, United States. 9. Roswell Park Cancer Institute, Elm and Carlton Street, Buffalo, NY 14263, United States.
Abstract
INTRODUCTION: To assess the efficacy and the Src-kinase inhibitor saracatinib (AZD-0530) after four cycles of platinum-based chemotherapy for extensive stage small cell lung cancer (SCLC). METHODS: Patients with at least stable disease received saracatinib at a dose of 175 mg/day by mouth until disease progression, unacceptable toxicity, or patient refusal. The primary endpoint was the 12-week progression-free survival (PFS) rate from initiation of saracatinib treatment. Planned interim analysis in first 20 patients, where 13 or more patients alive and progression-free at 12-weeks would allow continued enrollment to 40 total patients. RESULTS: All 23 evaluable patients received platinum based standard chemotherapy. Median age was 58 years (range: 48-82). 96% of patients had a performance status of 0/1. Median of two cycles given (range: 1-34). All 23 (100%) patients have ended treatment, most for disease progression (19/23). The 12-week PFS rate was 26% (6/23; 95% CI: 10-48%). From start of standard chemotherapy, median PFS was 4.7 months (95% CI: 4.5-5.1) and median OS was 11.2 months (95% CI: 9.9-13.8). Eight (35%) and three (13%) patients experienced at least one grade 3/4 or grade 4 AE, respectively. Commonly occurring grade 3/4 adverse events were thrombocytopenia (13%), fatigue (9%), nausea (9%), and vomiting (9%). CONCLUSIONS: Saracatinib at a dose of 175 mg/day by mouth is well tolerated. However, the PFS rate observed at the pre-planned interim analysis did not meet the criteria for additional enrollment.
INTRODUCTION: To assess the efficacy and the Src-kinase inhibitor saracatinib (AZD-0530) after four cycles of platinum-based chemotherapy for extensive stage small cell lung cancer (SCLC). METHODS:Patients with at least stable disease received saracatinib at a dose of 175 mg/day by mouth until disease progression, unacceptable toxicity, or patient refusal. The primary endpoint was the 12-week progression-free survival (PFS) rate from initiation of saracatinib treatment. Planned interim analysis in first 20 patients, where 13 or more patients alive and progression-free at 12-weeks would allow continued enrollment to 40 total patients. RESULTS: All 23 evaluable patients received platinum based standard chemotherapy. Median age was 58 years (range: 48-82). 96% of patients had a performance status of 0/1. Median of two cycles given (range: 1-34). All 23 (100%) patients have ended treatment, most for disease progression (19/23). The 12-week PFS rate was 26% (6/23; 95% CI: 10-48%). From start of standard chemotherapy, median PFS was 4.7 months (95% CI: 4.5-5.1) and median OS was 11.2 months (95% CI: 9.9-13.8). Eight (35%) and three (13%) patients experienced at least one grade 3/4 or grade 4 AE, respectively. Commonly occurring grade 3/4 adverse events were thrombocytopenia (13%), fatigue (9%), nausea (9%), and vomiting (9%). CONCLUSIONS:Saracatinib at a dose of 175 mg/day by mouth is well tolerated. However, the PFS rate observed at the pre-planned interim analysis did not meet the criteria for additional enrollment.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Stein Sundstrøm; Roy M Bremnes; Stein Kaasa; Ulf Aasebø; Reidulv Hatlevoll; Ragnar Dahle; Nils Boye; Mari Wang; Tor Vigander; Jan Vilsvik; Eva Skovlund; Einar Hannisdal; Steinar Aamdal Journal: J Clin Oncol Date: 2002-12-15 Impact factor: 44.544
Authors: G K Dy; A A Miller; S J Mandrekar; M-C Aubry; R M Langdon; R F Morton; S E Schild; J R Jett; A A Adjei Journal: Ann Oncol Date: 2005-08-08 Impact factor: 32.976
Authors: Frances A Shepherd; Giuseppe Giaccone; Lesley Seymour; Channa Debruyne; Andrea Bezjak; Vera Hirsh; Michael Smylie; Sheldon Rubin; Heidi Martins; Alan Lamont; Maciej Krzakowski; Anna Sadura; Benny Zee Journal: J Clin Oncol Date: 2002-11-15 Impact factor: 44.544
Authors: C Mascaux; M Paesmans; T Berghmans; F Branle; J J Lafitte; F Lemaitre; A P Meert; P Vermylen; J P Sculier Journal: Lung Cancer Date: 2000-10 Impact factor: 5.705
Authors: D V Skarlos; E Samantas; P Kosmidis; G Fountzilas; M Angelidou; P Palamidas; N Mylonakis; A Provata; E Papadakis; G Klouvas Journal: Ann Oncol Date: 1994-09 Impact factor: 32.976
Authors: S M Reddy; S Kopetz; J Morris; N Parikh; W Qiao; M J Overman; D Fogelman; I Shureiqi; C Jacobs; Z Malik; C A Jimenez; R A Wolff; J L Abbruzzese; G Gallick; C Eng Journal: Invest New Drugs Date: 2015-06-12 Impact factor: 3.850
Authors: Ana Ruiz-Saenz; Farima Zahedi; Elliott Peterson; Ashley Yoo; Courtney A Dreyer; Danislav S Spassov; Juan Oses-Prieto; Alma Burlingame; Mark M Moasser Journal: Mol Cancer Res Date: 2021-03-16 Impact factor: 5.852
Authors: Luigi Formisano; Valentina D'Amato; Alberto Servetto; Simona Brillante; Lucia Raimondo; Concetta Di Mauro; Roberta Marciano; Roberta Clara Orsini; Sandro Cosconati; Antonio Randazzo; Sarah J Parsons; Nunzia Montuori; Bianca Maria Veneziani; Sabino De Placido; Roberta Rosa; Roberto Bianco Journal: Oncotarget Date: 2015-09-22