THE ROLE OF HEMOGLOBIN LEVEL IN PREDICTING THE RESPONSE TO FIRST-LINE CHEMOTHERAPY IN ADVANCED COLORECTAL CANCER (ACC) PATIENTS

Background: Several in vitro studies showed that colorectal cancer cells responding to 5-fluorouracil (5-FU) become resistant under hypoxic conditions. 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 two 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 pts were submitted to 5-FU-based first-line chemotherapy. 184 pts received 5-FU ± folinic acid (FA); 195 pts received 5-FU + LOHP ± FA; 15 pts received 5-FU + CPT-11 ± FA. Hemoglobin levels were evaluated before chemotherapy start. Pts with hemoglobin < 12 g/dl were considered anemic. Response was evaluated every three cycles 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 after adjusting for PS, grading, T, or age in multivariate logistic analysis. Patients with normal hemoglobin levels showed a longer time to progression (13.0 months versus 10.1; P < 0.002) and a longer survival (27.6 months versus 17.8; P < 0.0001) than anemic ones. Cox’s multivariate survival analysis confirmed hemoglobin level as an independent predictor of time to progression and survival. Conclusions: Anemia is a strong predictive factor of activity and efficacy of 5-fluorouracil-based chemotherapy in advanced colorectal cancer patients