Clinical predictors of severe toxicity in patients treated with combination chemotherapy with irinotecan and/or oxaliplatin for metastatic colorectal cancer

Introduction

Little has been published regarding clinical predictors of severe toxicity in patients with metastatic colorectal cancer (CRC) treated with combination chemotherapy (CT) with oxaliplatin and/or irinotecan.

Material and Methods

We analyzed retrospectively 142 patients treated between 1996 and 2004 in our center with these regimes with regards to grade 3–4 toxicity and overall survival (OS) rates. Köhne's prognostic classification could be applied in all patients.

Results

Köhne classification: good (54.2%), intermediate (26.8%), and poor prognosis (19%). 50.4% received irinotecan-based CT. Median number of cycles 6 with a total response rate of 38.9%. 23.2% stopped first-line CT due to toxicity. 50.7% suffered grade 3–4 toxicity: digestive (28.2%), hematologic (19.7%), and fatigue (25.4%). 7.7% episodes of neutropenic fever with 4.9% toxic deaths. 70.9% of grade 3–4 episodes occurred in the first four cycles. Median follow-up of 33.9 mo; median OS of 15.9 mo. For Köhne classification: good (20 mo), intermediate (15.8 mo), and poor (6.8 mo). Toxicity analysis: female sex and age>70 yr predicted higher overall grade 3–4 toxicity, with no differences in CT efficacy; age>70 yr and PS>1 predicted higher grade 3–4 fatigue. No relationship could be found between baseline laboratory characteristics and higher toxicity, except baseline hemoglobin and grade 3–4 hematologic toxicity.

Conclusions

Female and elderly patients have a higher grade 3–4 toxicity rate when treated with combination CT with oxaliplatin or irinotecan. Prognostic classifications such as Köhne's can help differentiate subgroups of patients who benefit little with the use of combination CT.