A phase II study of capecitabine and lapatinib in advanced refractory colorectal adenocarcinoma: A Wisconsin Oncology
Background:
Prognosis remains poor after progression on first-line chemotherapy for colorectal adenocarcinoma, and inactivation of the EGFR pathway with monoclonal antibodies is an effective treatment strategy in selected patients with metastatic disease. Lapatinib is an oral EGFR and HER-2 dual tyrosine kinase inhibitor that has not shown significant activity in metastatic colorectal cancer. However, lapatinib may act synergistically with capecitabine in anticancer effects.
Methods:
This was an open-label, non-randomized phase II study of lapatinib 1,250 mg orally daily and capecitabine 2,000 mg/m(2) by mouth split into twice-daily dosing for 14 days of a 21 days cycle. Inclusion criteria included metastatic or locally advanced adenocarcinoma of the colon or rectum with progression by RECIST on or within six months of receiving a fluoridopyrimidine-, oxaliplatin- or irinotecan-containing regimen. Prior EGFR monoclonal antibody was permitted. K-ras testing was not routinely performed and was not a part of the study protocol.
Results:
Twenty nine patients (16 M; 13 F) were enrolled in this study. There were no complete or partial responses. 41.4% of patients achieved stable disease as a best response. Median overall survival was 6.8 months, with a 1-year survival rate of 22%, and median progression-free survival was 2.1 months. The combination produced few grade 3 and no grade 4 toxicities. No grade 3 toxicity occurred in more than 10% of patients.
Conclusions:
Although capecitabine and lapatinib is well tolerated, it is not an effective regimen in patients with refractory colorectal adenocarcinoma.
Insights
This study found that combining lapatinib and capecitabine did not improve outcomes for patients with refractory colorectal adenocarcinoma. The treatment was well-tolerated but showed no significant anticancer activity.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Colorectal adenocarcinoma prognosis is poor after first-line chemotherapy.
- EGFR pathway inhibitors are effective for selected metastatic colorectal cancer patients.
- Lapatinib, an oral EGFR/HER-2 inhibitor, showed limited activity alone but potential synergy with capecitabine.
Purpose of the Study:
- To evaluate the efficacy and safety of combining lapatinib with capecitabine in patients with refractory metastatic colorectal adenocarcinoma.
- To assess response rates, overall survival, and progression-free survival.
Main Methods:
- An open-label, non-randomized phase II study.
- 29 patients with metastatic or locally advanced colorectal adenocarcinoma received lapatinib (1,250 mg daily) and capecitabine (2,000 mg/m² twice daily for 14 of 21 days).
- Patients had progressed on prior fluoropyrimidine, oxaliplatin, or irinotecan regimens; prior EGFR antibody use was permitted.
Main Results:
- No complete or partial responses were observed.
- 41.4% of patients achieved stable disease.
- Median overall survival was 6.8 months, with a 1-year survival rate of 22%.
- Median progression-free survival was 2.1 months.
- The combination was well-tolerated with few grade 3 toxicities and no grade 4 toxicities.
Conclusions:
- The combination of capecitabine and lapatinib is well-tolerated in patients with refractory colorectal adenocarcinoma.
- This regimen is not effective in improving outcomes for this patient population.
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