Friedman G D
Division of Research, Kaiser Permanente Medical Care Program, Oakland, California 94611, USA.
Pharmacoepidemiol Drug Saf. 1997 Mar;6(2):129-34. doi: 10.1002/(SICI)1099-1557(199703)6:2<129::AID-PDS253>3.0.CO;2-H.
In up to 21 years of follow-up in a study to periodically screen pharmaceuticals for possible carcinogenic effects, 1146 persons who received lindane, an established carcinogen in animal experiments, showed for the first time a statistically significant increase in incidence of cancer (43 cases observed, 30.2 expected, standardized morbidity ratio 1.42, 95% confidence interval 1.03-1.92). The computer-stored data on drug dispensing and cancer occurrence also showed some evidence of a dose-response relationship. Review of the complete medical records suggested that at least part of the association was due to confounding by indication. Four of the cancer patients had Kaposi's sarcoma due to AIDS and the acquisition of pediculosis pubis or scabies, commonly treated with lindane, is associated with behaviour that also predisposes to AIDS. Four other patients also had strong risk factors that could readily be blamed for their cancer and one had not used the drug. Also, the location of the skin lesions or infestations treated with lindane seemed to bear no relation to the cancer sites. It is concluded that this study provides no convincing evidence of carcinogenicity of lindane; nor does it rule it out. In pharmacoepidemiology, it is advisable to supplement analyses of routinely collected data on drugs and clinical events with review of medical records when interesting associations are noted.
在一项定期筛查药物潜在致癌作用的长达21年的随访研究中,1146名接受林丹(动物实验中已证实的致癌物)治疗的患者首次出现癌症发病率在统计学上显著增加(观察到43例,预期30.2例,标准化发病比为1.42,95%置信区间为1.03 - 1.92)。计算机存储的药物配给和癌症发生数据也显示出一些剂量反应关系的证据。对完整病历的审查表明,至少部分关联是由于适应证的混杂因素所致。4名癌症患者患有艾滋病相关的卡波西肉瘤,而获得阴虱病或疥疮(通常用林丹治疗)与易患艾滋病的行为有关。另外4名患者也有很强的风险因素,很容易被认为是其患癌的原因,还有1名患者未使用该药物。此外,用林丹治疗的皮肤病变或感染部位似乎与癌症部位无关。结论是,本研究没有提供令人信服的证据证明林丹具有致癌性;也不能排除其致癌性。在药物流行病学中,当注意到有趣的关联时,除了对常规收集的药物和临床事件数据进行分析外,最好还对病历进行审查。