BACKGROUND: Pegylated liposomal doxorubicin has activity in both breast and ovarian cancer. Preclinical data noted that ZD1839 acts synergistically with chemotherapy. Given the lack of cross-resistance between these two agents, a phase I trial was initiated examining the safety and efficacy of the combination of liposomal doxorubicin and ZD1839 in patients with recurrent gynecologic or metastatic breast cancer. METHODS: Dose-limiting toxicity (DLT) was defined within the first two cycles of treatment. Escalating doses of liposomal doxorubicin were administered every 4 weeks with ZD1839. Pharmacokinetic analysis and correlative studies were performed. RESULTS: Thirty-five patients were enrolled in this study: six in each cohort. One DLT (febrile neutropenia) was observed in cohort 2. Dose level 3 was determined to be the maximum tolerated dose (MTD), and an additional ten patients were accrued. Serious adverse events (SAEs) included one patient with mental status changes believed secondary to disease progression and two central nervous system (CNS) bleeds believed to be unrelated to the combination of study agents. Toxicities were generally mild except for skin and gastrointestinal toxicity. No cardiac toxicity was observed. The best response to therapy included four partial responses and 20 patients with stable disease. CONCLUSIONS: Liposomal doxorubicin with ZD1839 is an active regimen but is associated with increased skin toxicity in patients with advanced breast and gynecologic cancer.
BACKGROUND: Pegylated liposomal doxorubicin has activity in both breast and ovarian cancer. Preclinical data noted that ZD1839 acts synergistically with chemotherapy. Given the lack of cross-resistance between these two agents, a phase I trial was initiated examining the safety and efficacy of the combination of liposomal doxorubicin and ZD1839 in patients with recurrent gynecologic or metastatic breast cancer. METHODS: Dose-limiting toxicity (DLT) was defined within the first two cycles of treatment. Escalating doses of liposomal doxorubicin were administered every 4 weeks with ZD1839. Pharmacokinetic analysis and correlative studies were performed. RESULTS: Thirty-five patients were enrolled in this study: six in each cohort. One DLT (febrile neutropenia) was observed in cohort 2. Dose level 3 was determined to be the maximum tolerated dose (MTD), and an additional ten patients were accrued. Serious adverse events (SAEs) included one patient with mental status changes believed secondary to disease progression and two central nervous system (CNS) bleeds believed to be unrelated to the combination of study agents. Toxicities were generally mild except for skin and gastrointestinal toxicity. No cardiac toxicity was observed. The best response to therapy included four partial responses and 20 patients with stable disease. CONCLUSIONS: Liposomal doxorubicin with ZD1839 is an active regimen but is associated with increased skin toxicity in patients with advanced breast and gynecologic cancer.
Authors: Susana Campos; Oday Hamid; Michael V Seiden; Amit Oza; Marie Plante; Ronald K Potkul; Peter F Lenehan; Eric P Kaldjian; Mary L Varterasian; Cheryl Jordan; Claudie Charbonneau; Hal Hirte Journal: J Clin Oncol Date: 2005-08-20 Impact factor: 44.544
Authors: Michael S Gordon; Daniela Matei; Carol Aghajanian; Ursula A Matulonis; Molly Brewer; Gini F Fleming; John D Hainsworth; Agustin A Garcia; Mark D Pegram; Russell J Schilder; David E Cohn; Lynda Roman; Mika K Derynck; Kimmie Ng; Benjamin Lyons; David E Allison; David A Eberhard; Thinh Q Pham; Randall C Dere; Beth Y Karlan Journal: J Clin Oncol Date: 2006-08-08 Impact factor: 44.544
Authors: F Ciardiello; R Caputo; R Bianco; V Damiano; G Pomatico; S De Placido; A R Bianco; G Tortora Journal: Clin Cancer Res Date: 2000-05 Impact factor: 12.531
Authors: Vincent A Miller; David H Johnson; Lee M Krug; Barbara Pizzo; Leslie Tyson; Wendy Perez; Peggy Krozely; Alan Sandler; David Carbone; Robert T Heelan; Mark G Kris; Robert Smith; Judith Ochs Journal: J Clin Oncol Date: 2003-06-01 Impact factor: 44.544
Authors: M E R O'Brien; N Wigler; M Inbar; R Rosso; E Grischke; A Santoro; R Catane; D G Kieback; P Tomczak; S P Ackland; F Orlandi; L Mellars; L Alland; C Tendler Journal: Ann Oncol Date: 2004-03 Impact factor: 32.976
Authors: Jessica E Pritchard; Patrick M Dillon; Mark R Conaway; Corinne M Silva; Sarah J Parsons Journal: Oncology Date: 2012-09-05 Impact factor: 2.935
Authors: Jo Morrison; Clemens Thoma; Richard J Goodall; Thomas J Lyons; Kezia Gaitskell; Alison J Wiggans; Andrew Bryant Journal: Cochrane Database Syst Rev Date: 2018-10-16