A total of 343 patients with previously untreated metastatic measurable colorectal carcinoma were studied to evaluate the impact on toxicity, response, and survival of leucovorin-modulated fluorouracil (5-FU). A maximally tolerated intravenous bolus loading course regimen of 5-FU alone (500 mg/m2 x 5 days every 4 weeks with 25 mg/m2 escalation) was compared with a high-dose leucovorin regimen (600 mg/m2 of 5-FU with 500 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest) and with a similar low-dose leucovorin regimen (600 mg/m2 of 5-FU with 25 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest). The dose-limiting toxicity for the two 5-FU and leucovorin regimens was gastrointestinal, specifically diarrhea; severe diarrhea was seen frequently, and treatment-related toxicity was implicated in the demise of 11 of the patients (5%). Significant improvements in response rates were observed with a response rate of 33 of 109 (30.3%) on the high-dose leucovorin regimen (P less than .01 v control); 13 of 107 (12.1%) on the 5-FU control; and 21 of 112 (18.8%) on the low-dose leucovorin regimen. A trend toward longer survival in the 5-FU plus high-dose leucovorin regimen was observed. In this study, leucovorin was shown to significantly enhance the therapeutic effect of 5-FU in metastatic colorectal carcinoma.
Review of the consultation records of the Gastrointestinal Surgical Oncology service at Roswell Park Memorial Institute from 1982 to 1987 revealed 22 patients with a finical diagnosis of neutropenic enterocolitis. Ninety one percent of the patients had hematologic malignancies and 95% were receiving cytotoxic chemotherapy, Sixteen patients were treated nonsurgically; 11 died. Of those 11 cases, autopsies were performed in 9. At autopsy, the clinical diagnosis was confirmed in four cases; four cases were found to have normal intestinal tracts, and one case had a small bowel volvulus. In none of the four cases for which autopsy proved neutropenic enterocolitis was transmural bowel necrosis or perforation found. Laparotomy was performed in six patients; three survived. The clinical diagnosis was verified in four of the six patients. Neutropenic enterocolitis must be considered a diagnosis of exclusion. Care of these patients should be individualized. Nonoperative management with bowel rest, decompression, nutritional support, and broad spectrum antibiotics is recommended initially. Operative intervention is recommended for those with perforation or those whose condition deteriorates clinically during close, frequent observation.
Background. Cancer is most common in older age groups, but little information is available with regard to the impact of age on chemotherapy toxicity. This study was undertaken to determine if age is an independent risk factor for 5‐fluorouracil (5‐FU) toxicity. Methods. Toxicity data from a prospective, randomized, multiinstitution trial of 5‐FU‐based treatment for advanced colorectal cancer were analyzed. Toxicity for each organ system was graded. Individual organ toxicity proportions were compared using chi‐square analysis. A logistic regression was performed using age (younger than 70 years vs. 70 years or older), sex, treatment arm, performance status, and length of therapy as model parameters to predict severe toxicity. Toxicity in 331 patients was analyzed. Results. Advanced age was significantly associated with the occurrence of any severe toxicity (58 vs. 36%, P < 0.001), leukopenia (24 vs. 10%, P < 0.005), diarrhea (24 vs. 14%, P = 0.01), vomiting (15 vs. 5%, P = 0.01), severe toxicity in more than 2 organ systems (10 vs. 3%, P = 0.02), and treatment mortality (9 vs. 2%, P = 0.01). By univariate analysis, age (P < 0.001) and sex (P < 0.0001) were independent predictors of severe toxicity. Twenty‐two of 27 women age 70 years or older had severe toxicity. Conclusions. Age 70 years or older and sex are risk factors for severe toxicity from 5‐FU‐based chemotherapy. Advanced age does not contraindicate the use of this type of chemotherapy, but close monitoring for multiple organ toxicities and vigorous supportive care of those with toxicity are required. Dosing decisions in older patients are difficult and must integrate assessments of organ function, comorbidities, overall physical status, and goals of treatment, in an effort to ensure the best possible outcome for these patients.
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