Phase II trial of a novel capecitabine dosing schedule in combination with lapatinib for the treatment of patients with HER2-positive metastatic breast cancer Journal Article
| Authors: | Gajria, D.; Gonzalez, J.; Feigin, K.; Patil, S.; Chen, C.; Theodoulou, M.; Drullinsky, P.; D'Andrea, G.; Lake, D.; Norton, L.; Hudis, C. A.; Traina, T. A. |
| Article Title: | Phase II trial of a novel capecitabine dosing schedule in combination with lapatinib for the treatment of patients with HER2-positive metastatic breast cancer |
| Abstract: | Our group applied mathematical modeling to capecitabine dosing and predicted 7 days of treatment followed by 7 days of rest (7-7) would improve efficacy and minimize toxicity. The conventional schedule of capecitabine limits full dosing in combination with other agents due to toxicity. Lapatinib inhibits the tyrosine kinase of HER2 and has activity when added to conventionally scheduled capecitabine for the treatment of patients with trastuzumab-refractory, HER2-positive, metastatic breast cancer (MBC). We performed this study to evaluate the activity and tolerability of capecitabine 7-7 with lapatinib in patients with trastuzumab-refractory MBC. Eligible patients had measurable, HER2-positive, MBC that progressed following exposure to trastuzumab. Treatment consisted of capecitabine 2,000 mg orally twice daily, 7-7 and lapatinib 1,250 mg orally daily. The primary endpoint was response rate. Secondary endpoints included toxicity, progression-free survival, and stable disease ≥6 months. Twenty-three patients were treated on study. More than 60% had prior chemotherapy for MBC and all had prior trastuzumab. After a median of 23 weeks (range 2-96+), five patients had partial responses (23; 95 CI, 7-44%) and six (27; 95 CI, 10-48%) had stable disease ≥6 months. Median progression-free survival was 9.4 months. The most common treatment-related toxicities ≥ grade (gr) 2 were hand-foot syndrome (gr 2 43%; gr 3 4% gr 4 0%), diarrhea (gr 2 26%; gr 3/4 0%), elevated liver chemistries (gr 2 17%; gr 3/4 0%), and anemia (gr 2 13%; gr 3 4%; gr 4 4%). No grade ≥3 nausea, vomiting, or diarrhea events occurred. This study demonstrated feasibility and after meeting biostatistical requirements for continued accrual was terminated in anticipation of slow enrollment. Capecitabine 7-7 with lapatinib was well tolerated with minimal gastrointestinal toxicity. Antitumor activity was observed in patients with trastuzumab-refractory MBC. © 2011 Springer Science+Business Media, LLC. |
| Keywords: | adult; clinical article; treatment outcome; aged; disease-free survival; middle aged; drug tolerability; fatigue; neutropenia; fluorouracil; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; capecitabine; progression free survival; phase 2 clinical trial; sensory neuropathy; breast cancer; anemia; antimetabolites, antineoplastic; mucosa inflammation; nausea; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; drug administration schedule; drug resistance, neoplasm; breast neoplasms; protein kinase inhibitors; drug response; acne; receptor, erbb-2; cancer control; hand foot syndrome; deoxycytidine; quinazolines; ataxia; lapatinib; hypertransaminasemia; her2-positive; antibodies, monoclonal, humanized |
| Journal Title: | Breast Cancer Research and Treatment |
| Volume: | 131 |
| Issue: | 1 |
| ISSN: | 0167-6806 |
| Publisher: | Springer |
| Date Published: | 2012-01-01 |
| Start Page: | 111 |
| End Page: | 116 |
| Language: | English |
| DOI: | 10.1007/s10549-011-1749-y |
| PROVIDER: | scopus |
| PUBMED: | 21898114 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 March 2012" - "CODEN: BCTRD" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work