BACKGROUND: Dual anti-HER2 therapy is effective for HER2-amplified breast cancer. Weekly paclitaxel, trastuzumab, and full-dose lapatinib (PTL) is not feasible because of grade 3 diarrhea. We conducted a phase II feasibility study of dose-dense (DD; every other week) PTL (ClinicalTrials.gov identifier, NCT01827163). PATIENTS AND METHODS: Eligible patients had HER2-positive breast cancer, tumor size ≤ 3 cm, and negative nodes. Treatment included paclitaxel (175 mg/m(2) × 4, every 2 weeks with pegfilgrastim), trastuzumab (4 mg/kg load and then 2 mg/kg weekly), and lapatinib (1000 mg daily). After paclitaxel × 4, trastuzumab (6 mg/kg every 3 weeks) plus lapatinib were continued for 1 year. The primary endpoint was feasibility, defined as (1) > 80% of patients completing PTL without a dose delay or reduction, (2) grade 3 diarrhea rate < 20%, and (3) cardiac event rate < 4%. RESULTS: From May 2013 to November 2013, we enrolled 20 of 55 planned patients. The median age was 49 years (range, 34-74 years). One patient had immediate paclitaxel hypersensitivity and was deemed inevaluable. Only 13 of 19 evaluable patients (68%) completed PTL without a dose delay or reduction or unacceptable toxicities. Only 3 of 19 (16%) had grade 3 diarrhea. Rash was frequent, with all grades in 18 of 19 (95%) and grade 3 in 2 of 19 (11%). The study was stopped early because of excess toxicity. CONCLUSION: The discontinuation rate during DD PTL was high, owing, in part, to an unexpectedly high incidence of rash. The trial was halted, because the initial discontinuation rate from overall toxicity made it unlikely that full accrual would demonstrate feasibility.
BACKGROUND: Dual anti-HER2 therapy is effective for HER2-amplified breast cancer. Weekly paclitaxel, trastuzumab, and full-dose lapatinib (PTL) is not feasible because of grade 3 diarrhea. We conducted a phase II feasibility study of dose-dense (DD; every other week) PTL (ClinicalTrials.gov identifier, NCT01827163). PATIENTS AND METHODS: Eligible patients had HER2-positive breast cancer, tumor size ≤ 3 cm, and negative nodes. Treatment included paclitaxel (175 mg/m(2) × 4, every 2 weeks with pegfilgrastim), trastuzumab (4 mg/kg load and then 2 mg/kg weekly), and lapatinib (1000 mg daily). After paclitaxel × 4, trastuzumab (6 mg/kg every 3 weeks) plus lapatinib were continued for 1 year. The primary endpoint was feasibility, defined as (1) > 80% of patients completing PTL without a dose delay or reduction, (2) grade 3 diarrhea rate < 20%, and (3) cardiac event rate < 4%. RESULTS: From May 2013 to November 2013, we enrolled 20 of 55 planned patients. The median age was 49 years (range, 34-74 years). One patient had immediate paclitaxelhypersensitivity and was deemed inevaluable. Only 13 of 19 evaluable patients (68%) completed PTL without a dose delay or reduction or unacceptable toxicities. Only 3 of 19 (16%) had grade 3 diarrhea. Rash was frequent, with all grades in 18 of 19 (95%) and grade 3 in 2 of 19 (11%). The study was stopped early because of excess toxicity. CONCLUSION: The discontinuation rate during DDPTL was high, owing, in part, to an unexpectedly high incidence of rash. The trial was halted, because the initial discontinuation rate from overall toxicity made it unlikely that full accrual would demonstrate feasibility.
Authors: Jeffrey M Albert; Aman U Buzdar; Reina Guzman; Pamela K Allen; Eric A Strom; George H Perkins; Wendy A Woodward; Karen E Hoffman; Welela Tereffe; Kelly K Hunt; Thomas A Buchholz; Julia L Oh Journal: Breast Cancer Res Treat Date: 2011-05-08 Impact factor: 4.872
Authors: Angelo Di Leo; Henry L Gomez; Zeba Aziz; Zanete Zvirbule; Jose Bines; Michael C Arbushites; Stephanie F Guerrera; Maria Koehler; Cristina Oliva; Steven H Stein; Lisa S Williams; Judy Dering; Richard S Finn; Michael F Press Journal: J Clin Oncol Date: 2008-10-27 Impact factor: 44.544
Authors: John P Crown; Harold A Burris; Fran Boyle; Suzanne Jones; Maria Koehler; Beth O Newstat; Roma Parikh; Cristina Oliva; Alaknanda Preston; Julie Byrne; Steve Chan Journal: Breast Cancer Res Treat Date: 2008-01-20 Impact factor: 4.872
Authors: J Crown; M J Kennedy; P Tresca; M Marty; M Espie; H A Burris; M DeSilvio; M R Lau; D Kothari; K M Koch; V Diéras Journal: Ann Oncol Date: 2013-08 Impact factor: 32.976
Authors: M E Lacouture; S M Laabs; M Koehler; R W Sweetman; A J Preston; A Di Leo; H L Gomez; V M Salazar; J A Byrne; K M Koch; K L Blackwell Journal: Breast Cancer Res Treat Date: 2008-07-04 Impact factor: 4.872
Authors: I Craig Henderson; Donald A Berry; George D Demetri; Constance T Cirrincione; Lori J Goldstein; Silvana Martino; James N Ingle; M Robert Cooper; Daniel F Hayes; Katherine H Tkaczuk; Gini Fleming; James F Holland; David B Duggan; John T Carpenter; Emil Frei; Richard L Schilsky; William C Wood; Hyman B Muss; Larry Norton Journal: J Clin Oncol Date: 2003-03-15 Impact factor: 44.544