Humoral hypercalcemia in patients with colorectal carcinoma: report of two cases and review of the literature.

BACKGROUND: Humoral hypercalcemia rarely is associated with colorectal carcinoma; to the authors' knowledge only nine cases have been reported to date. METHODS: Two cases of advanced colorectal carcinoma with humoral hypercalcemia of malignancy (HHM) are presented. RESULTS: The two patients had severe hypercalcemia without bone metastases. The diagnosis of HHM was based on findings of hypercalcemia, hypophosphoremia, elevated serum parathyroid hormone-related peptide (PTHrP), and positive tumor immunoreactivity to monoclonal PTHrP antiserum. One patient had a colonic adenocarcinoma with a neuroendocrine component and the other patient had rectal adenocarcinoma. Immunoreactive PTHrP was found in both tumor components. Bisphosphonate treatment normalized the hypercalcemia within a few days but it recurred in the patients 2 weeks and 3 weeks later, respectively. The prognosis was extremely poor. CONCLUSIONS: To the authors' knowledge the two cases presented in the current study are the first to be reported with HHM-associated colorectal carcinoma with positive tumor immunoreactivity to PTHrP monoclonal antiserum.

Relationship between 5-fluorouracil (5-FU) dose intensity and therapeutic response in patients with advanced colorectal cancer receiving infusional therapy containing 5-FU.

BACKGROUND: A phase II prospective trial was carried out to study the concept of 5-fluorouracil (5-FU) dose-intensity in patients with advanced colorectal cancer. Forty patients were treated with 5-FU plus leucovorin (LV), with individually increasing doses of 5-FU. A 5-FU pharmacokinetic follow up was performed and a relationship was sought between its metabolism and its response to treatment, and between 5-FU's toxicity and patient survival. METHODS: 5-FU was administered weekly by 8 hour continuous infusion. The initial dose of 1000 mg/m2 was individually increased every 3 weeks by 250 mg/m2 steps, potentiated by 400 mg/m2 LV. 5-FU plasma concentrations were determined weekly by liquid chromatography. RESULTS: Eighteen overall objective responses and 22 minor responses, stabilizations, or progressions (NR) were observed. 5-FU plasma levels were significantly higher in cases of complete or partial response, whatever the dose. They reached about 2000 micrograms/l as early as the second dose level (1250 mg/m2). Only seven patients who experienced NR reached equivalent levels after the fourth step (1750 mg/m2). High 5-FU plasma levels were predictive of an objective response and better survival (difference not significant). The acute toxicity, whatever the type, was correlated with 5-FU levels > 3000 micrograms/l and not with the dose. CONCLUSIONS: This study shows the wide variability of 5-FU metabolism, whatever the dose, the clear relationship between 5-FU plasma levels, toxicity, and efficacy. This relationship points out the problem of the polymorphism of 5-FU metabolism, the usefulness of the therapeutic range determination and the usefulness of the individual 5-FU dose adaptation.