Factors Influencing Survival in Stage IV Colorectal Cancer: The Influence of DNA Ploidy.

Objective. To evaluate the prognostic significance of microscopically assessed DNA ploidy and other clinical and laboratory parameters in stage IV colorectal cancer (CRC). Methods. 541 patients with histologically proven stage IV CRC treated with palliative chemotherapy at our institution were included in this retrospective analysis, and 9 variables (gender, age, performance status, carcinoembryonic antigen, cancer antigen 19-9, C-Reactive Protein (CRP), anaemia, hypoalbuminaemia, and ploidy (DNA Index)) were assessed for their potential relationship to survival. Results. Mean survival time was 12.8 months (95% confidence interval (CI) 12.0-13.5). Multivariate analysis revealed that DNA indexes of 2.2-3.6 and >3.6 were associated with 2.94 and 4.98 times higher probability of death, respectively, compared to DNA index <2.2. CRP levels of >15 mg/dL and 5-15 mg/dL were associated with 2.52 and 1.72 times higher risk of death, respectively. Hazard ratios ranged from 1.29 in patients mild anaemia (Hb 12-13.5 g/dL) to 1.88 in patients with severe anaemia (Hb < 8.5 g/dL). Similarly, the presence of hypoalbuminaemia (albumin < 5 g/dL) was found to confer 1.41 times inferior survival capability. Conclusions. Our findings suggest that patients with stage IV CRC with low ploidy score and CRP levels, absent or mild anaemia, and normal albumin levels might derive greatest benefit from palliative chemotherapy.

Predictors of survival in stage IV metastatic colorectal cancer.

UNLABELLED: The aim of this study was to evaluate predictors of survival in stage IV metastatic colorectal cancer (CRC). PATIENTS AND METHODS: A total of 541 patients with histologically proven metastatic CRC (UICC stage IV) were retrospectively analysed and 37 variables were tested for their potential relationship to survival. RESULTS: Mean survival time was recorded at 12.8 months [95% confidence interval (CI) 12.0-13.5]. Three factors were independently associated with improved survival: combination chemotherapy, improved performance status and dermatological complications. Eight factors were independently associated with unfavorable survival: worsened performance status, C-reactive protein >5 mg/dl, anemia, anorexia, weight loss > or =10%, fatigue, hypoalbuminemia and blood transfusions. CONCLUSION: A number of factors could be used as predictors of survival in patients with stage IV metastatic CRC. Patients who are relatively fit, have low CRP levels and tolerate combination chemotherapy appear to have a more favorable survival outcome.

Sequential administration of 5-fluorouracil (5FU)/leucovorin (LV) followed by irinotecan (CPT-11) at relapse versus CPT-11 followed by 5-FU/LV in advanced colorectal carcinoma. A phase III randomized study.

PURPOSE: The purpose of the present study was to evaluate the differences in the sequence of administration of 5-fluorouracil (5-FU)/leucovorin (LV) followed by irinotecan (CPT-11), or CPT-11 followed by 5-FU/LV in advanced colorectal cancer (ACC). PATIENTS AND METHODS: Chemotherapy-naïve patients with ACC were allocated to the following treatment groups: group A, a bolus of 20 mg/m(2) LV and 425 mg/m(2) 5-FU for 5 days until progression/relapse, and upon progression treatment with weekly CPT-11 (100 mg/m(2)), and group B, CPT-11 followed at progression/relapse by 5-FU/LV at the same doses and schedules as in group A. RESULTS: 120 patients were randomized to receive one of the two treatment sequences and their pretreatment characteristics were equally balanced between treatment arms. No statistically significant difference was found in the objective response rate to CPT-11 (p = 0.45); partial response (PR) was 23.3% for group A patients and 33.3% for group B. Following documented progression and second line treatment there was a significant difference between the response rate in group A (23.3%) and group B where no patients were found to respond to second-line treatment with 5-FU/LV (p = 0.024). The median overall survival was 42.0 weeks (range, 36.6-47.4 weeks) for group A and 32.0 weeks (range, 28.2-35.8 weeks) for group B. The median time to progression for patients in group A following first-line 5-FU/LV was 18 weeks (range, 10-36 weeks) and 12 weeks (range, 10-16 weeks) for group B following first-line CPT-11 (p = 0.0005). Toxicity, according to WHO, was similar between groups. CONCLUSIONS: Treating patients with CPT-11 upon progression to 5-FU/LV treatment seems to be superior to the opposite sequence. We used these treatments as sequential monotherapies (at progression/relapse), and the best results are gained when 5-FU/LV is followed by CPT-11 at disease progression or relapse.