Prescrire international
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Prescrire international · Jun 2006
Comparative StudyCinacalcet: new drug. Secondary hyperparathyroidism: where are the clinical data?
(1) Patients who require dialysis for chronic renal failure develop phosphocalcium metabolic disorders that often lead to secondary hyperparathyroidism. Standard treatment consists of a phosphate chelator and vitamin D, along with the use of an appropriate calcium concentration in the dialysis bath, but is difficult to manage. (2) Parathyroid cancer is a rare malignancy frequently associated with hypercalcaemia. (3) Cinacalcet is a calcimimetic agent that reduces the parathormone level. Clinical evaluation includes more than a dozen dose-finding studies and clinical trials. ⋯ Many adverse effects seen in animal studies have not been adequately investigated in the clinical setting, such as an increase in the QT interval, thyroid disorders, and sexual dysfunction. Cinacalcet is a powerful CYP 2D6 inhibitor and is also metabolised by isoenzymes CYP 3A4 and CYP 1A2, creating an increased risk of drug interactions. (8) In practice, treatment with cinacalcet seems difficult to manage and to provide only limited benefits. Available assessment reports leave many questions unanswered, and this is a further reason not to use this product outside of clinical trials, either after failure of phosphate chelator and vitamin D therapy (especially as an alternative to surgery) or in parathyroid cancer.
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Prescrire international · Jun 2006
Comparative StudyAdjuvant chemotherapy of colon cancer: lymph node involvement without metastases.
(1) The standard treatment for colon cancer is surgical excision, but without additional treatment nearly 50% of surgically treated patients die from relapse and metastatic disease progression. Adjuvant chemotherapy is designed to reduce the risk of post-surgical relapse. (2) The standard adjuvant chemotherapy is a combination of fluorouracil + folinic acid administered intravenously for 6 months (de Gramont protocol). (3) In patients with stage III disease (corresponding to Dukes stage C: lymph node involvement but no metastases), the 5-year survival rate after a 6-month course of fluorouracil + folinic acid is significantly higher than with placebo (63% versus 51%). The efficacy of this treatment has not been established in patients with stage II disease (no lymph node involvement or metastases), for whom the overall 5-year survival rate is about 80%. (4) In one trial a combination of oxaliplatin + fluorouracil + folinic acid (FOLFOX 4 protocol) failed to increase the overall 3-year survival rate more than the fluorouracil + folinic acid combination. It increased the event-free survival rate (72.2% versus 65.3%) but had more severe adverse effects, including: neuropathies (in about 12% of patients), neutropenia (41%), and gastrointestinal disturbances (5% to 10% of patients had nausea, vomiting and diarrhoea). (5) Capecitabine, a fluorouracil precursor, does not appear to be more effective than fluorouracil, but it does provide an alternative oral treatment with a slightly different profile of adverse effects (more frequent erythrodysesthesia, etc.). (6) In practice, adjuvant treatment with fluorouracil + folinic acid should be offered to patients with surgically treated stage-III colonic cancer.