BACKGROUND: This phase I/II trial was conducted to determine the toxicities, recommended dose, pharmacokinetics, and response rate of erlotinib plus trastuzumab in metastatic HER2+ breast cancer. PATIENTS AND METHODS: In phase I, sequential groups of patients with unlimited previous treatment received erlotinib at dose levels of 50, 100, and 150 mg plus standard dose weekly trastuzumab. In phase II, only patients with no previous chemotherapy or trastuzumab in the metastatic setting were allowed. RESULTS: The combination was well tolerated among the 16 patients enrolled in phase I, and the recommended phase II dose of erlotinib was initially set at 150 mg. After an interim review of the first 8 patients in phase II revealed a higher incidence of rash and diarrhea than expected from the phase I experience, the protocol was amended to treat new phase II patients at erlotinib 100 mg, with the opportunity to escalate to 150 mg after 3 weeks, based on individual patient tolerability. As a result of advances in other therapies aimed at HER2+ breast cancer, phase II closed before meeting its accrual goal. Among the 12 evaluable chemotherapy- and trastuzumab-naive patients treated at the recommended phase II dose level, there were 4 partial responses, and the time to progression was 9.03 months (95% CI, 1.2-undetermined). No pharmacokinetic interaction between the 2 agents was observed. CONCLUSION: The combination of erlotinib and trastuzumab was well tolerated when the dose of erlotinib was tailored to individual patient experience, and there was preliminary evidence of anticancer activity.
BACKGROUND: This phase I/II trial was conducted to determine the toxicities, recommended dose, pharmacokinetics, and response rate of erlotinib plus trastuzumab in metastatic HER2+ breast cancer. PATIENTS AND METHODS: In phase I, sequential groups of patients with unlimited previous treatment received erlotinib at dose levels of 50, 100, and 150 mg plus standard dose weekly trastuzumab. In phase II, only patients with no previous chemotherapy or trastuzumab in the metastatic setting were allowed. RESULTS: The combination was well tolerated among the 16 patients enrolled in phase I, and the recommended phase II dose of erlotinib was initially set at 150 mg. After an interim review of the first 8 patients in phase II revealed a higher incidence of rash and diarrhea than expected from the phase I experience, the protocol was amended to treat new phase II patients at erlotinib 100 mg, with the opportunity to escalate to 150 mg after 3 weeks, based on individual patient tolerability. As a result of advances in other therapies aimed at HER2+ breast cancer, phase II closed before meeting its accrual goal. Among the 12 evaluable chemotherapy- and trastuzumab-naive patients treated at the recommended phase II dose level, there were 4 partial responses, and the time to progression was 9.03 months (95% CI, 1.2-undetermined). No pharmacokinetic interaction between the 2 agents was observed. CONCLUSION: The combination of erlotinib and trastuzumab was well tolerated when the dose of erlotinib was tailored to individual patient experience, and there was preliminary evidence of anticancer activity.
Authors: Ian Smith; Marion Procter; Richard D Gelber; Sébastien Guillaume; Andrea Feyereislova; Mitch Dowsett; Aron Goldhirsch; Michael Untch; Gabriella Mariani; Jose Baselga; Manfred Kaufmann; David Cameron; Richard Bell; Jonas Bergh; Robert Coleman; Andrew Wardley; Nadia Harbeck; Roberto I Lopez; Peter Mallmann; Karen Gelmon; Nicholas Wilcken; Erik Wist; Pedro Sánchez Rovira; Martine J Piccart-Gebhart Journal: Lancet Date: 2007-01-06 Impact factor: 79.321
Authors: Charles L Vogel; Melody A Cobleigh; Debu Tripathy; John C Gutheil; Lyndsay N Harris; Louis Fehrenbacher; Dennis J Slamon; Maureen Murphy; William F Novotny; Michael Burchmore; Steven Shak; Stanford J Stewart; Michael Press Journal: J Clin Oncol Date: 2002-02-01 Impact factor: 44.544
Authors: N Normanno; M Campiglio; Luca A De; G Somenzi; M Maiello; F Ciardiello; L Gianni; D S Salomon; S Menard Journal: Ann Oncol Date: 2002-01 Impact factor: 32.976
Authors: Hyun-Soo Cho; Karen Mason; Kasra X Ramyar; Ann Marie Stanley; Sandra B Gabelli; Dan W Denney; Daniel J Leahy Journal: Nature Date: 2003-02-13 Impact factor: 49.962
Authors: Martine J Piccart-Gebhart; Marion Procter; Brian Leyland-Jones; Aron Goldhirsch; Michael Untch; Ian Smith; Luca Gianni; Jose Baselga; Richard Bell; Christian Jackisch; David Cameron; Mitch Dowsett; Carlos H Barrios; Günther Steger; Chiun-Shen Huang; Michael Andersson; Moshe Inbar; Mikhail Lichinitser; István Láng; Ulrike Nitz; Hiroji Iwata; Christoph Thomssen; Caroline Lohrisch; Thomas M Suter; Josef Rüschoff; Tamás Suto; Victoria Greatorex; Carol Ward; Carolyn Straehle; Eleanor McFadden; M Stella Dolci; Richard D Gelber Journal: N Engl J Med Date: 2005-10-20 Impact factor: 91.245
Authors: Edward H Romond; Edith A Perez; John Bryant; Vera J Suman; Charles E Geyer; Nancy E Davidson; Elizabeth Tan-Chiu; Silvana Martino; Soonmyung Paik; Peter A Kaufman; Sandra M Swain; Thomas M Pisansky; Louis Fehrenbacher; Leila A Kutteh; Victor G Vogel; Daniel W Visscher; Greg Yothers; Robert B Jenkins; Ann M Brown; Shaker R Dakhil; Eleftherios P Mamounas; Wilma L Lingle; Pamela M Klein; James N Ingle; Norman Wolmark Journal: N Engl J Med Date: 2005-10-20 Impact factor: 91.245
Authors: Ming Zhao; Ping He; Michelle A Rudek; Manuel Hidalgo; Sharyn D Baker Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2003-08-15 Impact factor: 3.205
Authors: Nicolas Martin; Nicolas Isambert; Carlos Gomez-Roca; Rainer-Georg Goeldner; Sylvie Zanetta; Behbood Sadrolhefazi; Hélène de Mont-Serrat; Mario Campone; Jean-Pierre Delord Journal: Cancer Chemother Pharmacol Date: 2018-10-22 Impact factor: 3.333