Nasti G, Errante D, Santarossa S, Vaccher E, Tirelli U
Division of Medical Oncology and AIDS, Centro di Riferimento Oncologico, Aviano, Pordenone, Italy.
Drug Saf. 1999 May;20(5):403-25. doi: 10.2165/00002018-199920050-00002.
Kaposi's sarcoma is the most common malignancy observed in patients with HIV-1 infection, and causes considerable morbidity and, when the lungs are involved, mortality. Therapy should be based on an evaluation of prognostic factors, in particular the extent and rate of tumour growth, patient symptoms, immune system condition and concurrent complications of AIDS. Nevertheless, considering the palliative role of Kaposi's sarcoma therapy, the potential benefits of therapy must be weighed against the high risk of adverse effects. Therefore, quality of life assessment is an integral component of therapeutic decisions. Localised Kaposi's sarcoma cutaneous tumours have been successfully treated with surgical excision, laser therapy, liquid nitrogen cryotherapy and radiotherapy. In patients with moderately extensive cutaneous or mucosal disease and CD4+ cell counts of > or =200/ml, immunotherapy and antiretroviral drugs are indicated. Preliminary results indicate that antiretroviral therapy might be effective and well tolerated in the treatment of less advanced Kaposi's sarcoma. In patients with aggressive and extensive mucocutaneous disease or with visceral manifestations of Kaposi's sarcoma, systemic cytotoxic therapy is indicated. However, the optimal treatment has yet to be found. The combination of doxorubicin, bleomycin and vincristine (ABV) has produced high overall response rates and is indicated as first-line treatment for patients with life-threatening or visceral disease. In patients who are leucopenic and require chemotherapy, single or dual agents associated with lower myelotoxicity [i.e. bleomycin, vincristine/vinblastine or a combination of bleomycin and vincristine/vinblastine (BV)] are most widely used. Other effective cytotoxic regimens are liposomal anthracyclines, paclitaxel and vinorelbine. To date, 3 randomised trials have compared these drugs to ABV and BV. In a large phase III study, the efficacy of liposomal daunorubicin was comparable with that of ABV. In 2 phase III studies, liposomal doxorubicin was compared with ABV and BV regimens and was found to be significantly more effective in producing objective responses. Therefore, liposomal doxorubicin, although more myelosuppressive than the BV regimen, is now considered by many physicians as the first-line therapy in patients with advanced stage Kaposi's sarcoma. Paclitaxel and vinorelbine have potential in Kaposi's sarcoma, but additional studies are needed to evaluate different schedules and to compare their activity with that of the reference regimens. Institution or continuation of both effective antiretroviral therapy and prophylaxis of opportunistic infections should be recommended to all patients receiving systemic cytotoxic therapies. However, attention must be paid to the cross-toxicity and possible pharmacokinetic interactions between antiretrovirals and antineoplastics.
卡波西肉瘤是人类免疫缺陷病毒1型(HIV-1)感染患者中最常见的恶性肿瘤,可导致相当高的发病率,若累及肺部则可导致死亡。治疗应基于对预后因素的评估,特别是肿瘤生长的范围和速度、患者症状、免疫系统状况以及艾滋病的并发并发症。然而,考虑到卡波西肉瘤治疗的姑息作用,必须权衡治疗的潜在益处与不良反应的高风险。因此,生活质量评估是治疗决策中不可或缺的组成部分。局限性卡波西肉瘤皮肤肿瘤已通过手术切除、激光治疗、液氮冷冻疗法和放射疗法成功治疗。对于中度广泛的皮肤或黏膜疾病且CD4+细胞计数≥200/ml的患者,可采用免疫疗法和抗逆转录病毒药物。初步结果表明,抗逆转录病毒疗法在治疗不太晚期的卡波西肉瘤时可能有效且耐受性良好。对于侵袭性和广泛的黏膜皮肤疾病或有卡波西肉瘤内脏表现的患者,应采用全身细胞毒性疗法。然而,最佳治疗方案尚未找到。阿霉素、博来霉素和长春新碱联合用药(ABV)已产生较高的总体缓解率,被指定为有生命危险或内脏疾病患者的一线治疗方案。对于白细胞减少且需要化疗的患者,最广泛使用的是骨髓毒性较低的单一或联合药物[即博来霉素、长春新碱/长春花碱或博来霉素与长春新碱/长春花碱联合用药(BV)]。其他有效的细胞毒性方案包括脂质体蒽环类药物、紫杉醇和长春瑞滨。迄今为止,已有3项随机试验将这些药物与ABV和BV进行了比较。在一项大型III期研究中,脂质体柔红霉素的疗效与ABV相当。在2项III期研究中,脂质体阿霉素与ABV和BV方案进行了比较,发现其在产生客观缓解方面明显更有效。因此,脂质体阿霉素虽然比BV方案的骨髓抑制作用更强,但现在许多医生认为它是晚期卡波西肉瘤患者的一线治疗方案。紫杉醇和长春瑞滨在卡波西肉瘤治疗中有潜力,但需要更多研究来评估不同的给药方案,并将它们的活性与参考方案进行比较。对于所有接受全身细胞毒性治疗的患者,都应建议进行有效的抗逆转录病毒治疗并预防机会性感染。然而,必须注意抗逆转录病毒药物和抗肿瘤药物之间的交叉毒性和可能的药代动力学相互作用。