Addition of cetuximab to oxaliplatin-based chemotherapy on liver and spleen size and thrombocytopenia in patients with metastatic colorectal cancer

Abstract

Introduction: A previous retrospective study revealed that oxaliplatin could induce splenic enlargement which in turn was associated with thrombocytopenia in patients with early stage colorectal cancer. However it has not still been known whether cetuximab aggravates or alleviates such effects in patients with metastatic colorectal cancer. We performed a retrospective study to investigate the effect of addition of cetuximab to oxaliplatin-based regimen as 1st line palliative chemotherapy on liver and spleen size and its association with thrombocytopenia in patients with metastatic colorectal cancer.

Methods: Ninety two consecutive patients with metastatic colorectal cancer, recruited from January 2008 to December 2011, received either oxaliplatin-based chemotherapy (XELOX or FOLFOX4, n=57) and the same regimen with cetuximab (n=35) as 1st line palliative chemotherapy for their metastatic colorectal cancer. Contrast-enhanced computed tomography (CT) scan was performed at baseline and after chemotherapy +/- cetuximab at regular intervals. The volumes of the residual liver after excluding liver metastases if present and spleen at baseline and after oxaliplatin-based chemotherapy +/- cetuximab were determined by contouring these organs in Eclipse Treatment Planning System version 8.9. Changes in volume of liver and spleen in all patients and subgroups stratified according to the use of cetuximab were compared by paired and independent sampled t-tests respectively. Binary logistic regression was performed for any factors predictive of thrombocytopenia defined as <100 x 109/l.

Results: Both liver (mean increase 4.2%, p=0.029) and spleen (mean increase 36.4%, p=0.000) enlarged in all patients after the use of oxaliplatin-based chemotherapy +/- cetuximab. Use of cetuximab in addition to oxaliplatin did not aggravate or protect the liver (mean decrease 0.56% for chemotherapy alone group vs mean increase 4.71% for cetuximab group, p=0.374) or spleen (mean increase 41.0% for chemotherapy alone group vs mean increase 31.9% for cetuximab group, p=0.338) from further change in size. Cumulative dose of cetuximab correlated with platelet count (Pearson's correlation coefficient r=0.503, p=0.020) and it was also associated with thrombocytopenia (relative risk: 4.563, p=0.033). However the risk of grade 3 or above (CTCAE version 4.0) thrombocytopenia was similar between those who received cetuximab and those who did not.

Conclusion: Oxaliplatin-based chemotherapy was confirmed to increase liver and spleen size in patients with metastatic colorectal cancer. Addition of cetuximab to oxaliplatin-based chemotherapy did not cause further hepatic or splenic enlargement but was associated with an increased chance of mild degree of thrombocytopenia.