Di Filippo Franco, Anzà Michele, Garinei Rosa, Cavaliere Francesco, Perri Pasquale, Botti Claudio, Di Angelo Piera, Di Filippo Simona, Maini Carlo Ludovico, Pasqualoni Rossella, Di Segni Susanna, Colantonio Simona, Bruno Pietro, Piarulli Loredana, Principi Francesca
Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy.
In Vivo. 2006 Nov-Dec;20(6A):735-8.
A combination of doxorubicin and tumor necrosis factor alpha (TNFalpha) has been proven to be very effective in the perfusional treatment of advanced soft tissue limb sarcoma both in terms of tumor necrosis and limb conservative surgery rate. Unfortunately, in some patients a grade IV limb reaction has been recorded. The key solution might be the use of liposomal doxorubicin (Caelyx) because the carrier seems to release the drug preferentially in the tumor rather than in the healthy tissue.
Twenty patients were treated with Caelyx: 14 with Caelyx alone and 6 in combination with a low TNFalpha dose (1 mg). In the first series of 14 patients a dose escalation study was carried out starting from a dose of 10 mg/L of limb volume. Six patients were treated with Caelyx (16 mg) and TNFalpha (1 mg).
The maximum tolerated dose (MTD) was 16 mg/L as in two patients treated with 18 mg/L a grade IV limb reaction was observed. Tumor response was satisfactory and conservative surgery was carried out in 13 patients. In 6 patients treated with Caelyx and TNFalpha, only a grade I limb reaction was recorded, thus, confirming that TNFalpha did not increase toxicity, at least at a dose of 1 mg. The Caelyx-TNFalpha combination did increase treatment efficacy. Tumor necrosis > or = 70% was observed in 4 out of 6 patients, one with 100% necrosis (pathological complete response). All the patients underwent conservative surgery.
The Caelyx-TNFalpha combination was proven to increase the efficacy of Caelyx alone, with a very low toxicity. These preliminary results have to be tested in a larger patient population.
已证实阿霉素与肿瘤坏死因子α（TNFα）联合用药在晚期肢体软组织肉瘤的灌注治疗中，无论是在肿瘤坏死还是肢体保肢手术率方面都非常有效。不幸的是，在一些患者中记录到了IV级肢体反应。关键的解决办法可能是使用脂质体阿霉素（凯素），因为载体似乎优先在肿瘤而非健康组织中释放药物。
20例患者接受了凯素治疗：14例单独使用凯素，6例与低剂量TNFα（1毫克）联合使用。在第一组14例患者中，从10毫克/升肢体体积的剂量开始进行了剂量递增研究。6例患者接受了凯素（16毫克）和TNFα（1毫克）治疗。
最大耐受剂量（MTD）为16毫克/升，因为在2例接受18毫克/升治疗的患者中观察到了IV级肢体反应。肿瘤反应令人满意，13例患者进行了保肢手术。在6例接受凯素和TNFα治疗的患者中，仅记录到I级肢体反应，因此，证实TNFα至少在1毫克剂量时不会增加毒性。凯素-TNFα联合用药确实提高了治疗效果。6例患者中有4例观察到肿瘤坏死≥70%，1例坏死率为100%（病理完全缓解）。所有患者均接受了保肢手术。
已证实凯素-TNFα联合用药可提高单独使用凯素的疗效，且毒性非常低。这些初步结果必须在更大的患者群体中进行验证。
