The role of hemoglobin level in predicting the response to first-line chemotherapy in advanced colorectal cancer (ACC)

Background: Several in vitro studies showed that colorectal cancer cells responding to 5-fluorouracil (5FU) become resistant under hypoxic condition. Moreover, it has been demonstrated that tumoral tissues are hypoxic in anemic pts. We investigated the impact of hemoglobin levels in predicting response to first-line chemotherapy in ACC patients. Methods: We collected data from 394 consecutive patients treated and followed in 2 centers from 1994 to 2003. Two hundred and forty five pts were men and 149 women. Median age: 61 years (29–80); WHO performance status (PS) 0/I/II: 279/90/25 pts; number of organs involved 1/2/3: 267/104/23 pts; metastases (mts) in liver were evident in 71% pts; mts in lung in 28% pts; mts in peritoneum in 19% pts; prior adjuvant chemotherapy was administered in 30% pts. All the pts were submitted to 5-FU-based first-line chemotherapy. 184 pts received 5FU ± folinic acid (FA); 195 pts received 5FU+LOHP±FA; 15 pts received 5FU+CPT-11±FA. Hemoglobin levels were evaluated before chemotherapy start. Pts with hemoglobin < 12 g/dl were considered anemic. Response was evaluated every 3c with CT scan. Results: Clinical response (CR+PR) was recorded in 136 pts (34.6%), stable disease in 155 (39.9%) and progression in 103 (26.5%). At baseline, 170 pts (43.1%) were anemic. 45/170 anemic pts (26.5%) and 91/224 non anemic pts (40.6%) responded to chemotherapy (X2= 8.57; p<0.003). Anemia maintained its predictive role for disease response even adjusting for PS, grading, T, or age in multivariate logistic analysis. Pts with normal hemoglobin level showed a longer time to progression (13.0 mo vs 10.1; p<0.002) and a longer survival (27.6 mo vs 17.8; p<0.0001) than anemic ones. Cox's multivariate survival analysis confirmed hemoglobin level as a independent predictor of time to progression and survival. Conclusions: Anemia is a strong predictive factor of activity and efficacy of 5fluorouracil based chemotherapy in advanced colorectal cancer patients.