Prescrire international
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Prescrire international · Dec 2005
Comparative StudyChemotherapy of metastatic colorectal cancer: fluorouracil plus folinic acid and irinotecan or oxaliplatin.
(1) Following the recent introduction of several new cytotoxic agents, a new look at the role of chemotherapy in metastatic colorectal cancer is needed. (2) In one clinical trial of first-line treatment, fluorouracil + folinic acid infusion, after an initial bolus (LV-5FU2 protocol), was more effective and better tolerated than bolus administration alone (Mayo Clinic protocol). (3) Five comparative trials failed to show that raltitrexed was more effective than fluorouracil + folinic acid in first-line treatment, and it has more serious adverse effects. (4) There are no comparative trials of capecitabine or tegafur + uracil versus fluorouracil + folinic acid (LV-5FU2 protocol) in first-line treatment. (5) In three comparative randomised trials involving previously untreated patients, adjunction of oxaliplatin to the fluorouracil + folinic acid combination (FOLFOX protocol) increased both tumour response rate and progression-free survival (by about 2 months), but it also caused more neuropathies, severe diarrhea and severe neutropenia. (6) In two comparative trials of first-line treatment, adjunction of irinotecan to fluorouracil + folinic acid (FOLFIRI protocol) increased the median survival time by about 3 months, to 15-17 months, but increased the incidence of diarrhea, neutropenia, serious cardiovascular disorders and severe thrombosis. (7) In second-line treatment, irinotecan is the only properly assessed drug with a positive impact, prolonging survival compared with appropriate palliative care (34 months after diagnosis, versus 27 months). (8) In one comparative trial, first-line treatment with the FOLFOX protocol, followed by the FOLFIRI protocol, resulted in the same median survival time (21 months) as the reverse sequence. (9) In practice, the first-line treatment for metastatic colorectal cancer appears to be the fluorouracil + folinic acid combination (LV-5FU2 protocol) plus either oxaliplatin (FOLFOX protocol) or irinotecan (FOLFIRI protocol). The reference second-line treatment is the FOLFIRI protocol (or the FOLFOX protocol if the FOLFIRI protocol has already been used). These treatments were associated with the longest survival in one trial.
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Prescrire international · Dec 2005
Comparative StudyPregabalin: new drug. Very similar to gabapentin.
(1) The first-line treatment for partial epilepsy is carbamazepine monotherapy; gabapentin monotherapy is an alternative, given its lower risk of drug-drug interactions. (2) The standard treatment for neuropathic pain associated with diabetes or post-herpetic neuralgia is a tricyclic antidepressant, with gabapentin as an alternative. Few drugs are available in this setting, and their efficacy is often modest. (3) Pregabalin is a GABA analogue closely related to gabapentin. Both drugs are marketed by Pfizer. ⋯ Animal studies suggest a possible risk of haemangiosarcoma, although no human cases have yet been described. (10) Pregabalin, like gabapentin, is eliminated unchanged in urine, implying a limited risk of interactions involving cytochrome P450, and suggesting that the dose should be reduced in patients with even moderate renal failure (creatinine clearance below 60 ml/min). (11) In practice, pregabalin offers nothing new for patients with partial epilepsy, for whom several other antiepileptics are available. The few available treatments for neuropathic pain have limited efficacy, and pregabalin may therefore be tried when both tricyclics and gabapentin fail. However, it is in no way certain that pregabalin is effective in such patients, and comparative trials are lacking.
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Prescrire international · Dec 2005
Comparative StudyStrontium: new drug. Postmenopausal osteoporosis: too many unknowns.
(1) Strontium ranelate is marketed in the European Union for the treatment of postmenopausal osteoporosis. Strontium, a cation closely related to calcium, was already used for this purpose in the 1950s but was abandoned because it caused bone mineralization disorders (mainly due to the high doses used at the time). (2) Strontium has only been compared with placebo: there are no clinical trials versus a diphosphonate. (3) On the basis of bone mineral density, two dose-finding studies suggested that, in women who are also taking calcium and vitamin D, the effective minimal dose of strontium is 1 g/day for primary prevention and 2 g/day for secondary prevention. (4) In secondary prevention, a randomised, double-blind trial (SOTI) involving 1649 postmenopausal women who had already had an osteoporotic fracture and were also taking calcium + vitamin D, showed that 2 g strontium daily reduced the risk of symptomatic vertebral fractures compared with placebo (11.3% versus 17.4%) after three years of treatment. (5) Another randomised, double-blind trial (TROPOS) involved 5091 women with osteoporosis of the femur. After three years of treatment with calcium, vitamin D, and either 2 g/day strontium or placebo, the risk of non vertebral osteoporotic fracture was lower in the strontium arm (10.9% versus 9.1%; relative risk 0.85, 95% confidence interval 0.71-1.01), although the difference was only just significant (p = 0.05). ⋯ Strontium can affect mental functions, and this effect needs to be quantified. Neurological and muscular adverse effects were inadequately documented, although disorders of this type were observed in animals. (8) The long-term adverse effects of strontium on bone (osteomalacia, pathological fractures, etc.) are unknown. Data from experimental studies and dialysis patients with renal failure raise the possibility of these adverse effects. (9) In practice, there are too many unknowns surrounding the potential risks of strontium while there is not enough evidence of clinical advantages over diphosphonates.