Purpose
The systemic administration of irinotecan with cetuximab has recently evolved as standard of care in irinotecan-refractory unresectable metastatic colorectal cancer (mCRC) patients (pts) with a response rate of 22% (Cunningham et al NEJM 2005). As a prelude to potentiating the responses of this regimen we postulated that the addition of a liver-directed therapy could be justified if the liver was the predominant focus of progression and treatment failure. To that end, we reviewed the sites of disease progression in patients who had consecutively received this regimen at our institution.
Purpose
The systemic administration of irinotecan with cetuximab has recently evolved as standard of care in irinotecan-refractory unresectable metastatic colorectal cancer (mCRC) patients (pts) with a response rate of 22% (Cunningham et al,NEJM 2005). As a prelude to potentiating the responses of this regimen we postulated that the addition of a liver-directed therapy could be justified if the liver was the predominant focus of progression and treatment failure. To that end, we reviewed the sites of disease progression in patients who had consecutively received this regimen at our institution.
Material and methods
54 patients with mCRC who underwent treatment with a combination of cetuximab with irinotecan at our institution from 3/2004 to 8/2005 were identified from the central pharmacy records.51 pts were analyzed since 3 patients who had received intermittent therapy were excluded. Parameters assessed included patient demographics, sites of involvement before and after initiation of therapy, sites of progression after initiation of treatment, median duration of treatment and survival from initiation of this regimen. Metastatic ‘sites’ were categorized as hepatic, pulmonary, intra-peritoneal extra-hepatic, retroperitoneal, osseous and others.
Material and methods
54 patients with mCRC who underwent treatment with a combination of cetuximab with irinotecan at our institution from 3/2004 to 8/2005 were identified from the central pharmacy records. Fifty-one patients were analyzed since 3 patients who had received intermittent therapy were excluded. Parameters assessed included patient demographics, sites of involvement before and after initiation of therapy, sites of progression after initiation of treatment, median duration of treatment and survival from initiation of this regimen. Metastatic ‘sites’ were categorized as hepatic, pulmonary, intra-peritoneal extra-hepatic, retroperitoneal, osseous and others.
Results
51 patients (27m, 24f) median age 59 yrs (range 22 - 85 yrs) met study criteria. Of these 8 patients exhibited hepatic only, 13 extrahepatic only and 30 synchronous hepatic & extrahepatic metastases. Overall, 28/51 pts (55%) discontinued treatment due to disease progression; in this cohort hepatic metastases were present pretreatment in 20 patients. Post treatment, extrahepatic only progression was observed in16/20 patients (>4 sites in 2, 3 sites in 3, 2 sites in 7 & one site in 4 patients respectively). For the entire cohort (51 pts), median treatment duration was 9 weeks (mean 14.6 weeks) and median survival from treatment initiation was 7 months (mean 7.8 months).
Results
51 patients (27m, 24f) median age 59 yrs (range 22 - 85 yrs) met study criteria. Of these, 8 patients exhibited hepatic only disease, 13 extrahepatic, and 30 synchronous hepatic & extrahepatic metastases. Overall, 28/51 pts (55%) discontinued treatment due to disease progression; in this cohort hepatic metastases were present pretreatment in 20 patients. Following treatment with irinotecan/cetuximab, extrahepatic only progression was observed in 16 of these 20 patients. For the entire cohort (51 pts), median treatment duration was 9 weeks (mean 14.6 weeks) and median survival from treatment initiation was 7 months (mean 7.8 months).
Conclusion
In this review, the majority of mCRC patients treated with the combination of irinotecan with cetuximab demonstrated multisite involvement at the time of treatment initiation and progression. Although liver-directed therapy appears reasonable to promote local control in the presence of multisite involvement our finding suggests extrahepatic disease results in increased morbidity. Therefore, consideration of liver-directed therapy may be best in conjunction with systemic chemotherapy regardless of liver-only metastases.